This study examines the effects of the antibiotic chloramphenicol (CAP) on brain metabolism in freely moving rats using picosecond time-resolved fluorescence spectroscopy. The researchers found that CAP, in addition to inhibiting mitochondrial protein synthesis, also influences redox processes in the respiratory chain by producing a marked increase in fluorescent signal in the nucleus raphe dorsalis, indicating a rise in NADH concentration. This suggests CAP efficiently inhibits complex I of the respiratory chain, which could explain why it suppresses paradoxical sleep. The approach provides a novel method for evaluating drug effects on deep brain structures in vivo.
This study investigated the mobility of wild type and P301S mutant tau proteins tagged with fluorescent markers in primary cortical neurons. Fluorescence recovery after photobleaching was used to compare the recovery rates of tau and control fluorescent proteins in neuronal cell bodies and axons. The results showed that both tau variants recovered fluorescence more slowly than controls but similarly to each other, indicating that the P301S mutation does not alter tau mobility. This suggests the mutation may affect tau function through other mechanisms.
This document summarizes a study that used picosecond optical tomography with a white laser and streak camera to measure changes in oxyhemoglobin and deoxyhemoglobin concentration in the brains of zebra finches in response to auditory stimulation. The technique showed submicromolar sensitivity and was able to resolve fast changes in the hippocampus and auditory forebrain with 250 μm resolution. Stimulation resulted in an early decrease in hemoglobin and oxyhemoglobin levels, followed by an increase in blood oxygen availability and pronounced vasodilation after stimulus end. The findings provide direct evidence linking blood oxygen level-dependent signals to changes in oxygen transport in birds.
This document summarizes a study that used functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) to measure hemodynamic changes in the brain of zebra finches in response to hypercapnia. Hypercapnia induces vasodilation and is often used to model hemodynamic responses. Both fMRI, which detects blood oxygen level-dependent (BOLD) signals, and NIRS, which measures concentrations of oxyhemoglobin and deoxyhemoglobin, clearly showed increases in blood oxygen saturation in the brain during hypercapnia. The results provide the first correlation in songbirds between hemodynamic parameter variations measured by NIRS and local BOLD signal variations measured by fMRI.
This study provides evidence that correlated neural activity can propagate through multiple stages of a neural circuit involved in song production in songbirds. The researchers recorded neural activity simultaneously from two or three song nuclei - LMAN, RA, and HVc. They found correlated activity between neuron firing in these nuclei, both during spontaneous activity and in response to auditory stimuli like the bird's own song. This correlated activity persisted even when the activity in one nucleus (HVc) was disrupted. This suggests the song circuit contains highly interconnected neurons that can preserve timing information about groups of neural firing through multiple synaptic connections. Since this song circuit is important for vocal learning, preserving correlated activity may be important for learning and producing sequenced motor behaviors.
Study to compare the DHFR enzyme activity when exposure to He-Ne laser and UV...IOSR Journals
In the present work 100 white laboratory mice(Mus musculus) were exposed to He-Ne laser and UVC(1h) radiation for the area of testis .These numbers were divided into five groups : first group is a control (10 mice),second group was exposed to He-Ne laser(27 mice ) and this divided into three subgroups for (5min,10min,15min), third group(9 mice) were exposed to UVC for (1h) , fourth group(27 mice) were exposed to laser firstly and UVC(1h) with duration time 1/2 h and this group is divided into three subgroups for (5min,10min,15min)for laser radiation, finally fifth group(27 mice) was exposed to UVC (1h)first and laser with duration time 1/2 h, which divided to three subgroups for (5min,10min,15min)for laser radiation. In the testis of mice, the results of DHFR enzyme in UVC show the mean value and standard deviation was(318.1583±56.41706) ,the enzyme activity increased gradually and significantly with UVC(1h)and the correlation between normal and UVC value is significant .The mean value and standard deviation of DHFR enzyme in laser 5min was(26.2500±6.35580), while the mean value and standard deviation of DHFR enzyme in laser 10min was (33.3833±13.95155).The mean value and standard deviation of DHFR enzyme in laser 15 min was (23.4250±9.26767).The correlation between normal and laser (5,10,15min) value is not significant .The mean value and standard deviation of DHFR enzyme in laser 5min+UVC(1h) was( 17.3450±4.34567).The correlation between normal and laser 5min+UVC(1h) value is significant. The mean value and standard deviation of DHFR enzyme in laser 10min +UVC(1h) was (19.4667±8.87891).The mean value and standard deviation of DHFR enzyme in laser15 min+ UVC(1h) was (39.3400±31.51039).The correlation between normal and laser10,15min+UVC(1h) value is not significant. The mean value and standard deviation of DHFR enzyme in UVC(1h)+laser5min was (55.1833±22.63580), .The mean value and standard deviation of DHFR enzyme in UVC(1h)+laser10min was (42.0383±11.18429).Finally the mean value and standard deviation of DHFR enzyme in UVC(1h)+laser15min was(36.1017±19.51019).The correlation between normal and UVC(1h) +laser 5,10,15 min value is significant.
This document reviews the use of quantum dots for bioimaging applications. It discusses:
1) The synthesis of quantum dots, particularly CdSe/ZnS core/shell structures, and methods to tune their optical properties.
2) Modification of quantum dot surfaces with ligands to make them water soluble and biocompatible while maintaining fluorescence. Common surface modifications include adding carboxylic acids, silica shells, and encapsulation in micelles.
3) Applications of quantum dots in biology, including labeling of proteins and targeting of specific cell surface receptors due to their photostability and ability to detect multiple signals simultaneously.
FSM 2015 - International Biophysics ConferenceDirk Hähnel
Fluorescence Spectroscopy, Microscopy and Molecular Cell
Mechanics
Program and Abstract Book
8th – 11th October 2015
Pollentia Club Resort, 07400 Alcúdia, Spain
Event organizer:
Georg August University
Third Institute of Physics
Dirk Hähnel
Friedrich Hund Platz 1
37077 Göttingen, Germany
A New Frontier of Precision Medicine: Using PET for Image-Guided Neurointerve...InsideScientific
A New Frontier of Precision Medicine: Using PET for Image-Guided Neurointerventions
Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to share on Email (Opens in new window)
ON DEMAND
Experts discuss how PET/CT imaging can be used to enable image-guided neurointerventions and to study targeted delivery and clearance of therapeutic agents.
WATCH WEBINAR
Mice are by far the most frequently used animal for modeling disease and developing therapeutic strategies including neurointerventions. However, due to its anatomical and physiological barriers, the brain is a difficult target for delivery of therapeutic agents. Systemic administration is plagued with marginal brain accumulation and high risk of off-target side effects.
In this webinar sponsored by Scintica Instrumentation, Dr. Piotr Walczak, Dr. Mirosław Janowski and Dr. Wojciech Lesniak address this challenge and discuss why advanced imaging is essential to perform image-guided neurointerventions.
First, Dr. Janowski provides rationale as to how imaging can be used to better understand how therapeutic agents are delivered to the brain and subsequently cleared. Next, Dr. Walczak reviews methodological and technological advances for improving precision and reproducibility of brain targeting in mice based on MRI and two-photon microscopy. Finally, Dr. Lesniak presents recently-published results using ARGUS PET/CT to quantify intra-artrial delivery of antibodies, nanobodies and poly(amidoamine) dendrimers.
Key Learning Objectives Include:
- Why advanced imaging is essential to perform image-guided neurointerventions
- Why we need to visualize not only penetration of therapeutic agents to the brain, but also their clearance
- How image-guided procedures can be used to visualize and optimize delivery of therapeutic agents to the brain
This study investigated the mobility of wild type and P301S mutant tau proteins tagged with fluorescent markers in primary cortical neurons. Fluorescence recovery after photobleaching was used to compare the recovery rates of tau and control fluorescent proteins in neuronal cell bodies and axons. The results showed that both tau variants recovered fluorescence more slowly than controls but similarly to each other, indicating that the P301S mutation does not alter tau mobility. This suggests the mutation may affect tau function through other mechanisms.
This document summarizes a study that used picosecond optical tomography with a white laser and streak camera to measure changes in oxyhemoglobin and deoxyhemoglobin concentration in the brains of zebra finches in response to auditory stimulation. The technique showed submicromolar sensitivity and was able to resolve fast changes in the hippocampus and auditory forebrain with 250 μm resolution. Stimulation resulted in an early decrease in hemoglobin and oxyhemoglobin levels, followed by an increase in blood oxygen availability and pronounced vasodilation after stimulus end. The findings provide direct evidence linking blood oxygen level-dependent signals to changes in oxygen transport in birds.
This document summarizes a study that used functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) to measure hemodynamic changes in the brain of zebra finches in response to hypercapnia. Hypercapnia induces vasodilation and is often used to model hemodynamic responses. Both fMRI, which detects blood oxygen level-dependent (BOLD) signals, and NIRS, which measures concentrations of oxyhemoglobin and deoxyhemoglobin, clearly showed increases in blood oxygen saturation in the brain during hypercapnia. The results provide the first correlation in songbirds between hemodynamic parameter variations measured by NIRS and local BOLD signal variations measured by fMRI.
This study provides evidence that correlated neural activity can propagate through multiple stages of a neural circuit involved in song production in songbirds. The researchers recorded neural activity simultaneously from two or three song nuclei - LMAN, RA, and HVc. They found correlated activity between neuron firing in these nuclei, both during spontaneous activity and in response to auditory stimuli like the bird's own song. This correlated activity persisted even when the activity in one nucleus (HVc) was disrupted. This suggests the song circuit contains highly interconnected neurons that can preserve timing information about groups of neural firing through multiple synaptic connections. Since this song circuit is important for vocal learning, preserving correlated activity may be important for learning and producing sequenced motor behaviors.
Study to compare the DHFR enzyme activity when exposure to He-Ne laser and UV...IOSR Journals
In the present work 100 white laboratory mice(Mus musculus) were exposed to He-Ne laser and UVC(1h) radiation for the area of testis .These numbers were divided into five groups : first group is a control (10 mice),second group was exposed to He-Ne laser(27 mice ) and this divided into three subgroups for (5min,10min,15min), third group(9 mice) were exposed to UVC for (1h) , fourth group(27 mice) were exposed to laser firstly and UVC(1h) with duration time 1/2 h and this group is divided into three subgroups for (5min,10min,15min)for laser radiation, finally fifth group(27 mice) was exposed to UVC (1h)first and laser with duration time 1/2 h, which divided to three subgroups for (5min,10min,15min)for laser radiation. In the testis of mice, the results of DHFR enzyme in UVC show the mean value and standard deviation was(318.1583±56.41706) ,the enzyme activity increased gradually and significantly with UVC(1h)and the correlation between normal and UVC value is significant .The mean value and standard deviation of DHFR enzyme in laser 5min was(26.2500±6.35580), while the mean value and standard deviation of DHFR enzyme in laser 10min was (33.3833±13.95155).The mean value and standard deviation of DHFR enzyme in laser 15 min was (23.4250±9.26767).The correlation between normal and laser (5,10,15min) value is not significant .The mean value and standard deviation of DHFR enzyme in laser 5min+UVC(1h) was( 17.3450±4.34567).The correlation between normal and laser 5min+UVC(1h) value is significant. The mean value and standard deviation of DHFR enzyme in laser 10min +UVC(1h) was (19.4667±8.87891).The mean value and standard deviation of DHFR enzyme in laser15 min+ UVC(1h) was (39.3400±31.51039).The correlation between normal and laser10,15min+UVC(1h) value is not significant. The mean value and standard deviation of DHFR enzyme in UVC(1h)+laser5min was (55.1833±22.63580), .The mean value and standard deviation of DHFR enzyme in UVC(1h)+laser10min was (42.0383±11.18429).Finally the mean value and standard deviation of DHFR enzyme in UVC(1h)+laser15min was(36.1017±19.51019).The correlation between normal and UVC(1h) +laser 5,10,15 min value is significant.
This document reviews the use of quantum dots for bioimaging applications. It discusses:
1) The synthesis of quantum dots, particularly CdSe/ZnS core/shell structures, and methods to tune their optical properties.
2) Modification of quantum dot surfaces with ligands to make them water soluble and biocompatible while maintaining fluorescence. Common surface modifications include adding carboxylic acids, silica shells, and encapsulation in micelles.
3) Applications of quantum dots in biology, including labeling of proteins and targeting of specific cell surface receptors due to their photostability and ability to detect multiple signals simultaneously.
FSM 2015 - International Biophysics ConferenceDirk Hähnel
Fluorescence Spectroscopy, Microscopy and Molecular Cell
Mechanics
Program and Abstract Book
8th – 11th October 2015
Pollentia Club Resort, 07400 Alcúdia, Spain
Event organizer:
Georg August University
Third Institute of Physics
Dirk Hähnel
Friedrich Hund Platz 1
37077 Göttingen, Germany
A New Frontier of Precision Medicine: Using PET for Image-Guided Neurointerve...InsideScientific
A New Frontier of Precision Medicine: Using PET for Image-Guided Neurointerventions
Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to share on Email (Opens in new window)
ON DEMAND
Experts discuss how PET/CT imaging can be used to enable image-guided neurointerventions and to study targeted delivery and clearance of therapeutic agents.
WATCH WEBINAR
Mice are by far the most frequently used animal for modeling disease and developing therapeutic strategies including neurointerventions. However, due to its anatomical and physiological barriers, the brain is a difficult target for delivery of therapeutic agents. Systemic administration is plagued with marginal brain accumulation and high risk of off-target side effects.
In this webinar sponsored by Scintica Instrumentation, Dr. Piotr Walczak, Dr. Mirosław Janowski and Dr. Wojciech Lesniak address this challenge and discuss why advanced imaging is essential to perform image-guided neurointerventions.
First, Dr. Janowski provides rationale as to how imaging can be used to better understand how therapeutic agents are delivered to the brain and subsequently cleared. Next, Dr. Walczak reviews methodological and technological advances for improving precision and reproducibility of brain targeting in mice based on MRI and two-photon microscopy. Finally, Dr. Lesniak presents recently-published results using ARGUS PET/CT to quantify intra-artrial delivery of antibodies, nanobodies and poly(amidoamine) dendrimers.
Key Learning Objectives Include:
- Why advanced imaging is essential to perform image-guided neurointerventions
- Why we need to visualize not only penetration of therapeutic agents to the brain, but also their clearance
- How image-guided procedures can be used to visualize and optimize delivery of therapeutic agents to the brain
Label free and reagentless electrochemical detection of micro rn-as using a c...hbrothers
This document describes a label-free and reagentless electrochemical biosensor for detecting microRNAs (miRNAs). The sensor uses a conducting polymer nanostructured with carbon nanotubes that is electroactive in neutral aqueous solutions. Addition of the target miRNA miR-141, a prostate cancer biomarker, causes a "signal-on" response by increasing the current through the polymer. Non-complementary miRNAs do not change the current. The sensor achieves very low detection of about 8 femtomolar (fM) of miR-141. The conducting polymer-carbon nanotube composite provides a reagentless platform for immobilizing and detecting miRNA sequences with high sensitivity and specificity.
SuperArgus PET/CT: Advanced Pre-Clinical Imaging for Small to Medium AnimalsInsideScientific
Positron Emission Tomography (PET) is the gold standard in metabolic imaging, providing high sensitivity to radiotracers used to detect metabolic activity or biomarkers in vivo. The most common uses for PET imaging in pre-clinical research include oncology, neurobiology, cardiology and dynamic imaging.
In this Scintica Instrumentation webinar, Tonya Coulthard discusses how Position Emission Tomography is used for preclinical imaging. Tonya provides an overview of applications including real-time imaging of awake animals, self-gated cardiac imaging and multiplexed PET imaging of standard and non-standard isotopes.
She also intruduces the SuperArgus PET/CT system, which is ideally suited for preclinical imaging of small animals like mice up to medium-sized animals like swine and non human primates.
Key Discussion Topics Include:
- Overview of Pre-Clinical PET/CT imaging
- Examples from applications including oncology, neurology, cardiology and dynamic imaging
- An introduction to SuperArgus PET/CT and what makes it unique
Quantum dots and application in medical sciencekeyhan *
applications of quantum dots in medicine
Pharmacy and pharmacology
Bioimaiging (in vitro labelling , in vivo imaging)
Tumor & cancer target
Pathogen and toxin detection
Photothermal therapy (PTT)
photodynamic therapy (PDT)
Targeted surgery
Immunoassay
DNA analysis
biological monitoring
drug discovery
The PRIME center incorporates five departments - Radiology, Cell Biology, Nuclear Medicine, Rheumatology, and the Central Animal Laboratory - to provide multi-modal preclinical imaging. It aims to operate as a single-location facility with MRI, optical, PET, and SPECT imaging to allow experiments with transgenic animals and viruses. The center offers 7T and 11.7T MRI, multi-photon fluorescence microscopy, microPET/CT, microSPECT/CT, and an optical imaging system to study topics like tumor development, islet transplantation, infection models, and more. Researchers can access expertise and perform longitudinal studies with sub-cellular resolution across modalities to translate findings from small animals to human studies.
The document discusses the use of quantum dots (QDs) for biomedical applications such as bioimaging and therapy. It provides an overview of the photophysical properties of QDs that make them advantageous over organic dyes for imaging. Various biomedical applications of QDs are described, including in vitro and in vivo imaging, biosensing, photodynamic therapy, drug delivery, and gene delivery. Finally, the document outlines a research proposal to develop MoS2@polyaniline nanohybrids for dual-model imaging and synergistic photothermal/radiation therapy of tumors.
Study of Mitotic Index and DNA profile when exposure to He-Ne laser and UVC r...IOSR Journals
This study examined the effects of He-Ne laser radiation and UVC radiation on mitotic index and DNA profiles in mice. 100 mice were divided into groups exposed to laser radiation at different time periods, UVC radiation for 1 hour, laser pre-exposure followed by UVC, and UVC pre-exposure followed by laser. Mitotic index, which measures the percentage of cells undergoing cell division, and DNA electrophoresis were analyzed at various time points after exposure. Results showed that UVC radiation decreased mitotic index and increased DNA damage over time, while laser pre-exposure protected against these effects of subsequent UVC exposure by inducing antioxidant defenses and DNA repair mechanisms. Laser exposure alone had minor effects on mitotic index.
This study evaluated the effectiveness of a 3-carboranyl thymidine analogue (3CTA), designated N5–2OH, as a boron delivery agent for boron neutron capture therapy (BNCT) of brain tumors. Target validation studies using wild-type and mutant thymidine kinase 1 (TK1) L929 cell lines implanted in mice found higher boron levels and tumor cell kill in TK1-expressing tumors after BNCT with N5–2OH. Subsequent studies in rats with intracerebral RG2 gliomas found significantly increased survival times when tumors were treated with either N5–2OH alone or combined with boronophenylalanine compared to boronophenyl
PET and SPECT Scanning: Functional Brain ImagingBrendan Quinn
PET and SPECT are functional brain imaging techniques. PET has higher resolution but is more expensive, while SPECT has lower resolution but is less expensive. Both techniques involve injecting radioactive tracers and detecting their location in the brain to map blood flow and metabolic activity. fMRI is another functional imaging technique that detects changes in blood oxygenation to map brain activity.
Gamma Knife radiosurgery provides a highly effective treatment for brain metastases, allowing for reliable local tumor control with a minimally invasive approach. It provides equivalent or superior outcomes to other standard treatments like surgical resection and fractionated radiotherapy. Studies show median survival times of 10-12 months for patients treated with radiosurgery alone or in combination with whole brain radiation. The risk of adverse side effects is low when established dose and volume criteria are followed for tumors under 30mm in diameter. Whole brain radiation does not seem to improve local control or survival when added to radiosurgery treatment.
PET-CT and PET-MR provide functional imaging through PET as well as anatomical imaging through CT or MRI. PET involves radiolabeling molecules like FDG with positron emitters, injecting them into patients, and using coincident detection of annihilation photons to construct 3D images. PET-CT provides accurate localization of functional abnormalities and distinction of normal from pathological tracer uptake. Whole-body PET-MRI is an emerging technique that combines the molecular imaging of PET with the excellent soft tissue contrast of MRI.
The document discusses small animal imaging techniques. It provides an overview of various imaging modalities including their resolutions and applications. Specific techniques covered include bioluminescence imaging, fluorescence imaging, computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography. The document also discusses fluorescent probes and reagents used for small animal imaging including near-infrared dyes, quantum dots, fluorescent microspheres, and protease-activatable probes. Potential applications highlighted include tumor detection, vascular imaging, and monitoring of enzyme activity.
This document compares the visual organs of insects and mammals. It discusses the similarities and differences in their phototransduction pathways and anatomical structures. Some key points:
- Both use opsins bound to retinal as the photosensitive pigment, but insects use different opsins than mammals and transduce light signals through different G proteins and second messengers.
- Compound eyes of insects like Drosophila are made of many individual ommatidia that each detect light from a different angle, while mammals have a single pupil and non-uniform retina.
- Photoreceptor cells in both hyperpolarize in response to light via different downstream mechanisms, but both require regeneration of the unexcited pigment form for
The speaker declares no conflicts of interest regarding the presentation. The presentation will discuss functional MRI (fMRI) and manganese-enhanced MRI (MEMRI) studies of the mouse brain. It will cover issues with BOLD fMRI in mice such as spatial resolution requirements and anesthesia effects. It will also discuss applications of MEMRI for mapping neural activity and connectivity in olfactory and auditory systems of mouse models.
This document discusses using an optic fiber sensor to measure levels of NADH (reduced form of nicotinamide adenine dinucleotide) in the rat brain during different sleep-wake states. The sensor allows for non-invasive, continuous measurements of NADH fluorescence in freely moving rats. Preliminary findings show NADH levels increase moderately in the periaqueductal gray-nucleus raphe dorsalis region during slow-wave sleep compared to waking, and increase more during paradoxical sleep. NADH levels in the cortex also increase moderately during slow-wave and paradoxical sleep compared to waking. Variations in NADH levels may reflect changes in brain oxidative energy metabolism across sleep-wake
1) Male zebra finches were found to respond differently to calls from their mate versus other females depending on their social context. Specifically, males responded much more to their mate's call when with a mated pair compared to when alone or with other unmated males.
2) Previous studies found male zebra finches did not show mate recognition from female calls. However, the new study found female calls contain identifiable acoustic features allowing for individual recognition.
3) The results suggest social context can influence mate recognition in birds, challenging the view that complex social assessments are unique to primates.
1) The document discusses preliminary studies using two-photon microscopy to image brain areas of zebra finches through their thin skin and hollow skull structure for non-invasive monitoring of brain activity.
2) Experiments were conducted imaging hollow fibers filled with Rhodamine B passed through fixed zebra finch skin and skull samples to evaluate spatial resolution and distortion. Reflectance confocal measurements were also taken to determine scattering properties of fresh and fixed skin and skull.
3) The goal is to determine if two-photon microscopy can provide sufficient resolution for in vivo brain imaging and metabolism monitoring of zebra finches as a model for studying vocal recognition, without requiring craniotomy as in other small animal studies.
This document describes an experiment that used near-infrared spectroscopy (NIRS) to noninvasively measure the optical properties of a songbird's brain. Researchers placed optical fibers on the head of anesthetized zebra finches to transmit laser light and collect the light after it passed through the brain tissue. They were able to measure the absorption and scattering coefficients of the caudal nidopallium region of the brain in vivo. This technique could help monitor brain activity and oxygenation levels in songbirds.
This document discusses limitations of the classical homogenization approach for modeling light absorption in tissues. It considers a two-dimensional model where light absorption occurs only within parallel, thin blood vessels and not in the surrounding tissue. The model contains three small parameters: E is the ratio of vessel spacing to tissue size, d is the ratio of vessel thickness to spacing, and v is a large parameter related to absorption strength within vessels. The paper shows that classical homogenization is valid when E→0, v→∞, d→0, and E2vd→0, but is invalid when E→0, v→∞, d→0, and E2vd2→∞, requiring non-classical asymptotic expans
This document describes the construction and characterization of recombinant viruses containing the HIV-1 env gene from seminal strains. The researchers amplified the V1-V3 region of env from seminal plasma samples and used it to construct chimeric viruses by co-transfecting the V1-V3 fragment into a V1-V3 deleted vector. Four chimeric viruses were able to replicate and were characterized as using CXCR4 as a coreceptor. Confocal microscopy was used to observe the interaction of the cell-free viral particles with reporter cell lines. The recombinant viruses representing seminal strains are useful tools for studying heterosexual HIV transmission and testing microbicides.
This document describes a new ultrafast Diffuse Optical Tomography (DOT) technique developed for real-time in vivo brain imaging of songbirds. The technique uses an amplified ultrafast laser and single-shot streak camera to measure the time of flight of photons through brain tissue. This allows for a 3D reconstruction of brain activity from space and time sampling of the reflectance signal. Preliminary results show the brain tissue response to hypercapnia stimulations can be detected.
Clinical Applications of Proton MR Spectroscopy.pdfSilvana Ciardullo
1) Proton MR spectroscopy provides greater tissue characterization than MR imaging alone by detecting metabolic abnormalities. It can be performed on most clinical 1.5T MR units in 10-15 minutes without significant additional scan time.
2) The technique detects metabolite concentrations based on peak intensities and locations on generated spectra graphs. The most commonly detected brain metabolites are NAA, creatine, choline, and lactate. Abnormal concentrations of these metabolites can indicate various neurological conditions.
3) Proton MR spectroscopy is useful for evaluating tumors, infections, demyelinating diseases, and other neurological disorders by detecting deviations from normal metabolite levels and ratios that provide physiological information about tissue status.
The document provides an overview of neuroimaging techniques used in psychiatry such as MRI, CT, PET, SPECT, fMRI, DTI, and MRS. It discusses the basic principles, milestones in development, and applications of these techniques. Specifically, it summarizes research using these neuroimaging methods that have found abnormalities in brain structure and function in patients with obsessive-compulsive disorder (OCD), such as reduced serotonin transporter binding in fronto-striatal circuits and differences in brain activity in regions like the thalamus and orbitofrontal cortex.
Label free and reagentless electrochemical detection of micro rn-as using a c...hbrothers
This document describes a label-free and reagentless electrochemical biosensor for detecting microRNAs (miRNAs). The sensor uses a conducting polymer nanostructured with carbon nanotubes that is electroactive in neutral aqueous solutions. Addition of the target miRNA miR-141, a prostate cancer biomarker, causes a "signal-on" response by increasing the current through the polymer. Non-complementary miRNAs do not change the current. The sensor achieves very low detection of about 8 femtomolar (fM) of miR-141. The conducting polymer-carbon nanotube composite provides a reagentless platform for immobilizing and detecting miRNA sequences with high sensitivity and specificity.
SuperArgus PET/CT: Advanced Pre-Clinical Imaging for Small to Medium AnimalsInsideScientific
Positron Emission Tomography (PET) is the gold standard in metabolic imaging, providing high sensitivity to radiotracers used to detect metabolic activity or biomarkers in vivo. The most common uses for PET imaging in pre-clinical research include oncology, neurobiology, cardiology and dynamic imaging.
In this Scintica Instrumentation webinar, Tonya Coulthard discusses how Position Emission Tomography is used for preclinical imaging. Tonya provides an overview of applications including real-time imaging of awake animals, self-gated cardiac imaging and multiplexed PET imaging of standard and non-standard isotopes.
She also intruduces the SuperArgus PET/CT system, which is ideally suited for preclinical imaging of small animals like mice up to medium-sized animals like swine and non human primates.
Key Discussion Topics Include:
- Overview of Pre-Clinical PET/CT imaging
- Examples from applications including oncology, neurology, cardiology and dynamic imaging
- An introduction to SuperArgus PET/CT and what makes it unique
Quantum dots and application in medical sciencekeyhan *
applications of quantum dots in medicine
Pharmacy and pharmacology
Bioimaiging (in vitro labelling , in vivo imaging)
Tumor & cancer target
Pathogen and toxin detection
Photothermal therapy (PTT)
photodynamic therapy (PDT)
Targeted surgery
Immunoassay
DNA analysis
biological monitoring
drug discovery
The PRIME center incorporates five departments - Radiology, Cell Biology, Nuclear Medicine, Rheumatology, and the Central Animal Laboratory - to provide multi-modal preclinical imaging. It aims to operate as a single-location facility with MRI, optical, PET, and SPECT imaging to allow experiments with transgenic animals and viruses. The center offers 7T and 11.7T MRI, multi-photon fluorescence microscopy, microPET/CT, microSPECT/CT, and an optical imaging system to study topics like tumor development, islet transplantation, infection models, and more. Researchers can access expertise and perform longitudinal studies with sub-cellular resolution across modalities to translate findings from small animals to human studies.
The document discusses the use of quantum dots (QDs) for biomedical applications such as bioimaging and therapy. It provides an overview of the photophysical properties of QDs that make them advantageous over organic dyes for imaging. Various biomedical applications of QDs are described, including in vitro and in vivo imaging, biosensing, photodynamic therapy, drug delivery, and gene delivery. Finally, the document outlines a research proposal to develop MoS2@polyaniline nanohybrids for dual-model imaging and synergistic photothermal/radiation therapy of tumors.
Study of Mitotic Index and DNA profile when exposure to He-Ne laser and UVC r...IOSR Journals
This study examined the effects of He-Ne laser radiation and UVC radiation on mitotic index and DNA profiles in mice. 100 mice were divided into groups exposed to laser radiation at different time periods, UVC radiation for 1 hour, laser pre-exposure followed by UVC, and UVC pre-exposure followed by laser. Mitotic index, which measures the percentage of cells undergoing cell division, and DNA electrophoresis were analyzed at various time points after exposure. Results showed that UVC radiation decreased mitotic index and increased DNA damage over time, while laser pre-exposure protected against these effects of subsequent UVC exposure by inducing antioxidant defenses and DNA repair mechanisms. Laser exposure alone had minor effects on mitotic index.
This study evaluated the effectiveness of a 3-carboranyl thymidine analogue (3CTA), designated N5–2OH, as a boron delivery agent for boron neutron capture therapy (BNCT) of brain tumors. Target validation studies using wild-type and mutant thymidine kinase 1 (TK1) L929 cell lines implanted in mice found higher boron levels and tumor cell kill in TK1-expressing tumors after BNCT with N5–2OH. Subsequent studies in rats with intracerebral RG2 gliomas found significantly increased survival times when tumors were treated with either N5–2OH alone or combined with boronophenylalanine compared to boronophenyl
PET and SPECT Scanning: Functional Brain ImagingBrendan Quinn
PET and SPECT are functional brain imaging techniques. PET has higher resolution but is more expensive, while SPECT has lower resolution but is less expensive. Both techniques involve injecting radioactive tracers and detecting their location in the brain to map blood flow and metabolic activity. fMRI is another functional imaging technique that detects changes in blood oxygenation to map brain activity.
Gamma Knife radiosurgery provides a highly effective treatment for brain metastases, allowing for reliable local tumor control with a minimally invasive approach. It provides equivalent or superior outcomes to other standard treatments like surgical resection and fractionated radiotherapy. Studies show median survival times of 10-12 months for patients treated with radiosurgery alone or in combination with whole brain radiation. The risk of adverse side effects is low when established dose and volume criteria are followed for tumors under 30mm in diameter. Whole brain radiation does not seem to improve local control or survival when added to radiosurgery treatment.
PET-CT and PET-MR provide functional imaging through PET as well as anatomical imaging through CT or MRI. PET involves radiolabeling molecules like FDG with positron emitters, injecting them into patients, and using coincident detection of annihilation photons to construct 3D images. PET-CT provides accurate localization of functional abnormalities and distinction of normal from pathological tracer uptake. Whole-body PET-MRI is an emerging technique that combines the molecular imaging of PET with the excellent soft tissue contrast of MRI.
The document discusses small animal imaging techniques. It provides an overview of various imaging modalities including their resolutions and applications. Specific techniques covered include bioluminescence imaging, fluorescence imaging, computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography. The document also discusses fluorescent probes and reagents used for small animal imaging including near-infrared dyes, quantum dots, fluorescent microspheres, and protease-activatable probes. Potential applications highlighted include tumor detection, vascular imaging, and monitoring of enzyme activity.
This document compares the visual organs of insects and mammals. It discusses the similarities and differences in their phototransduction pathways and anatomical structures. Some key points:
- Both use opsins bound to retinal as the photosensitive pigment, but insects use different opsins than mammals and transduce light signals through different G proteins and second messengers.
- Compound eyes of insects like Drosophila are made of many individual ommatidia that each detect light from a different angle, while mammals have a single pupil and non-uniform retina.
- Photoreceptor cells in both hyperpolarize in response to light via different downstream mechanisms, but both require regeneration of the unexcited pigment form for
The speaker declares no conflicts of interest regarding the presentation. The presentation will discuss functional MRI (fMRI) and manganese-enhanced MRI (MEMRI) studies of the mouse brain. It will cover issues with BOLD fMRI in mice such as spatial resolution requirements and anesthesia effects. It will also discuss applications of MEMRI for mapping neural activity and connectivity in olfactory and auditory systems of mouse models.
This document discusses using an optic fiber sensor to measure levels of NADH (reduced form of nicotinamide adenine dinucleotide) in the rat brain during different sleep-wake states. The sensor allows for non-invasive, continuous measurements of NADH fluorescence in freely moving rats. Preliminary findings show NADH levels increase moderately in the periaqueductal gray-nucleus raphe dorsalis region during slow-wave sleep compared to waking, and increase more during paradoxical sleep. NADH levels in the cortex also increase moderately during slow-wave and paradoxical sleep compared to waking. Variations in NADH levels may reflect changes in brain oxidative energy metabolism across sleep-wake
1) Male zebra finches were found to respond differently to calls from their mate versus other females depending on their social context. Specifically, males responded much more to their mate's call when with a mated pair compared to when alone or with other unmated males.
2) Previous studies found male zebra finches did not show mate recognition from female calls. However, the new study found female calls contain identifiable acoustic features allowing for individual recognition.
3) The results suggest social context can influence mate recognition in birds, challenging the view that complex social assessments are unique to primates.
1) The document discusses preliminary studies using two-photon microscopy to image brain areas of zebra finches through their thin skin and hollow skull structure for non-invasive monitoring of brain activity.
2) Experiments were conducted imaging hollow fibers filled with Rhodamine B passed through fixed zebra finch skin and skull samples to evaluate spatial resolution and distortion. Reflectance confocal measurements were also taken to determine scattering properties of fresh and fixed skin and skull.
3) The goal is to determine if two-photon microscopy can provide sufficient resolution for in vivo brain imaging and metabolism monitoring of zebra finches as a model for studying vocal recognition, without requiring craniotomy as in other small animal studies.
This document describes an experiment that used near-infrared spectroscopy (NIRS) to noninvasively measure the optical properties of a songbird's brain. Researchers placed optical fibers on the head of anesthetized zebra finches to transmit laser light and collect the light after it passed through the brain tissue. They were able to measure the absorption and scattering coefficients of the caudal nidopallium region of the brain in vivo. This technique could help monitor brain activity and oxygenation levels in songbirds.
This document discusses limitations of the classical homogenization approach for modeling light absorption in tissues. It considers a two-dimensional model where light absorption occurs only within parallel, thin blood vessels and not in the surrounding tissue. The model contains three small parameters: E is the ratio of vessel spacing to tissue size, d is the ratio of vessel thickness to spacing, and v is a large parameter related to absorption strength within vessels. The paper shows that classical homogenization is valid when E→0, v→∞, d→0, and E2vd→0, but is invalid when E→0, v→∞, d→0, and E2vd2→∞, requiring non-classical asymptotic expans
This document describes the construction and characterization of recombinant viruses containing the HIV-1 env gene from seminal strains. The researchers amplified the V1-V3 region of env from seminal plasma samples and used it to construct chimeric viruses by co-transfecting the V1-V3 fragment into a V1-V3 deleted vector. Four chimeric viruses were able to replicate and were characterized as using CXCR4 as a coreceptor. Confocal microscopy was used to observe the interaction of the cell-free viral particles with reporter cell lines. The recombinant viruses representing seminal strains are useful tools for studying heterosexual HIV transmission and testing microbicides.
This document describes a new ultrafast Diffuse Optical Tomography (DOT) technique developed for real-time in vivo brain imaging of songbirds. The technique uses an amplified ultrafast laser and single-shot streak camera to measure the time of flight of photons through brain tissue. This allows for a 3D reconstruction of brain activity from space and time sampling of the reflectance signal. Preliminary results show the brain tissue response to hypercapnia stimulations can be detected.
Clinical Applications of Proton MR Spectroscopy.pdfSilvana Ciardullo
1) Proton MR spectroscopy provides greater tissue characterization than MR imaging alone by detecting metabolic abnormalities. It can be performed on most clinical 1.5T MR units in 10-15 minutes without significant additional scan time.
2) The technique detects metabolite concentrations based on peak intensities and locations on generated spectra graphs. The most commonly detected brain metabolites are NAA, creatine, choline, and lactate. Abnormal concentrations of these metabolites can indicate various neurological conditions.
3) Proton MR spectroscopy is useful for evaluating tumors, infections, demyelinating diseases, and other neurological disorders by detecting deviations from normal metabolite levels and ratios that provide physiological information about tissue status.
The document provides an overview of neuroimaging techniques used in psychiatry such as MRI, CT, PET, SPECT, fMRI, DTI, and MRS. It discusses the basic principles, milestones in development, and applications of these techniques. Specifically, it summarizes research using these neuroimaging methods that have found abnormalities in brain structure and function in patients with obsessive-compulsive disorder (OCD), such as reduced serotonin transporter binding in fronto-striatal circuits and differences in brain activity in regions like the thalamus and orbitofrontal cortex.
MRI spectroscopy- Its Application, Principle & Techniques Nitish Virmani
Magnetic resonance spectroscopy (MRS) is a noninvasive imaging technique that measures biochemical and metabolic processes in tissues without using ionizing radiation. MRS provides additional clinical information for diseases such as brain tumors, metabolic disorders, and systemic diseases. MRS can distinguish between neoplastic and non-neoplastic brain masses, identify tumor recurrence versus radiation necrosis, and help monitor treatment response. Key metabolites that MRS evaluates include NAA, creatine, choline, lactate, lipids, and myo-inositol. Metabolite ratios are used for interpretation, with abnormal ratios indicating various conditions like tumors, demyelination, ischemia, and infection. MRS has wide clinical applications and provides valuable physiological information to
Micro-Neuro-Sensor Recording of STN Neurons of the Human BrainMangaiK4
Abstract-What cause to the neurons of the human brain cells when they are damaged. They become inactive. So damage to subthalamiuc ucleus (STN) neurons of the human brain causing larger involuntary movements and thereby attacking the Parkinson’s disease (PD). Deep brain stimulation (DBS) of bilateral sub thalamic nuclei (STN) is an efficient method of rehabilitation technique in subjects with advanced idiopathic Parkinson’s (or Parkinson) disease. Accurate targeting of STN neurons and placement of microelectrodes/ (neurosensors) are paramount importance for optimal results after STN-DBS method.In this paper, microminiaturized electrode recordings (MER) of STN neurons were detected in a mean of 3.5 ±1.1 channels on right hemisphere and 3.6 ±1.04 on left hemisphere.Final channel selected were most commonly central seen in 42.3% followed by anterior in 33.7%. When a high current is delivered to STN or GPi neurons of basal ganglia (a component of human brain), causing their inhibition and improved indication of symptoms. It is now known that there is a significant change in the firing pattern and a reorganization of the entire basal ganglia circuit with DBS. The MER of STN neurons has identified a specific high frequency irregular larger amplitude firing patterns seen only in disease states and hence used to detect the neurons of ST nucleus during functional surgery. Micro electrode recording is so useful to confirm the right path but has to be taken in consideration with effects on macro stimulation.
This study examined the effects of chronic exposure to nicotine on the function of human α4β2 nicotinic acetylcholine receptors (nAChRs), which play a major role in nicotine addiction. The key findings were:
1) Acetylcholine dose-response curves for human α4β2 nAChRs expressed in human cells were biphasic, consisting of both high- and low-affinity components.
2) Chronic exposure to nicotine or nicotinic antagonists increased the fraction of high-affinity receptors from 25% to around 70% and doubled the acetylcholine-evoked currents.
3) Upregulation of receptor function after chronic nicotine exposure occurred
1. The study found that NMDA receptor activation triggers an association between the tumor suppressor protein PTEN and the synaptic scaffolding protein PSD-95.
2. This association requires a PDZ-binding motif on PTEN and leads to PTEN being recruited to and anchored at dendritic spines.
3. Enhancing PTEN's lipid phosphatase activity was found to specifically drive depression of AMPA receptor-mediated synaptic responses, and this activity was required for NMDA receptor-dependent long-term depression (LTD) but not other forms of plasticity.
WIP is a negative regulator of neuronal maturation and synaptic activity. Mice lacking WIP (WIP-/-) have enlarged neuronal somas and overgrown neuritic and dendritic branches, especially during early development. WIP-/- neurons also have increased amplitude and frequency of miniature excitatory postsynaptic currents, indicating more mature synapses than in wild-type neurons. This reveals WIP as a previously unknown regulator of neuronal maturation and synaptic activity.
This study examined the binding of the nicotinic cholinergic antagonist dihydro-β-erythroidine ([3H]DBE) to rat brain tissue. The key findings were:
1) [3H]DBE bound to two sites in rat cortical membranes with dissociation constants of 4 nM and 22 nM. Binding was saturable, reversible, and susceptible to protein denaturation.
2) Binding was highest in the thalamus and lowest in the spinal cord. It showed preferential enrichment in synaptosomal subfractions.
3) Nicotine displaced [3H]DBE binding in a stereospecific manner, with (-)-nicotine being approximately 6 times more potent
There are two main types of MRI sequences: spin echo (SE) and gradient echo (GE). SE produces better image quality but has longer scan times, while GE has shorter scan times. Key MRI parameters are repetition time (TR) and echo time (TE). Different MRI weightings (T1, T2, PD, FLAIR) provide contrast between tissues. Advanced MRI techniques like DWI, PWI, and MRS provide additional clinical information on diffusion, perfusion, and metabolism. Functional MRI (fMRI) uses the BOLD contrast to non-invasively map functional brain activity with good spatial and temporal resolution. MRI and its variants are useful clinical tools for diagnosis, treatment planning, and studying brain
This document summarizes research on correlating MRI findings with neuropathological features in multiple sclerosis (MS). Key points include:
- MRI techniques like MTR can detect myelin and axonal loss validated by histology. Non-lesional white matter shows more extensive pathology than just lesions.
- Cortical grey matter also shows demyelination, neuronal loss, and atrophy correlated with disability.
- Spinal cord pathology including diffuse axonal loss and myelin damage contributes to disability, not just atrophy.
- Validating MRI with post-mortem tissue is important for diagnosis, predicting disease progression, and understanding substrates of disability in MS.
This document describes a study using a single 3D multi-echo gradient-recalled echo (ME-GRE) MRI sequence, both before and after injection of the contrast agent ferumoxytol, to generate multiple image contrasts of the human brain. The sequence was able to produce R2* maps, field maps, susceptibility-weighted imaging, time-of-flight angiography, and quantitative susceptibility maps from a single 5 minute 44 second scan. Preliminary results in a pediatric patient show the potential of this approach to provide complementary anatomical and vascular information from a single efficient scan.
PET scans use radioactive tracers and detectors to generate 3D images of metabolic processes in the body. They have various applications in neurology for diagnosing and monitoring conditions like dementia, epilepsy, movement disorders, and brain tumors. For example, PET can help differentiate Alzheimer's from other dementias based on patterns of hypometabolism in temporal and parietal lobes. It is also useful for localizing epileptic foci before epilepsy surgery. The document discusses the history, mechanisms, common tracers, and limitations of PET scanning as well as its role in evaluating specific neurological conditions and potential future applications.
Using multiple imaging techniques, the study found:
1) Fluorescence microscopy with transgenic mice expressing fluorescent reporters allowed visualization of axonal damage over time.
2) Confocal microscopy revealed reactive changes in axotomized neurons such as sprouting.
3) Multi-photon microscopy enabled in vivo and in vitro imaging at greater depths with less phototoxicity.
This document summarizes a study that used Fourier transform infrared (FT-IR) microspectroscopy to analyze chemical and structural changes in central nervous system (CNS) tissue during the induction and prevention of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The study found that FT-IR was able to detect subtle biochemical changes in CNS tissue before clinical signs of EAE appeared. It also found that FT-IR could distinguish between healthy and diseased tissue with high accuracy. Additionally, the study showed FT-IR could detect differences in CNS tissue from animals that were partially protected against EAE through vaccination.
Analysis of EEG Signal using nonextensive statisticsIRJET Journal
The document discusses the analysis of electroencephalogram (EEG) signals using Tsallis entropy, a measure of non-extensive statistics. It reviews 35 published papers that applied Tsallis entropy to analyze EEG data from both medical and non-medical domains. The key findings are:
1) Tsallis entropy performed better than Shannon entropy and other measures at discriminating changes in EEG data, suggesting it is well-suited to study complex brain systems with long-range interactions like EEG data.
2) Tsallis entropy has been successfully used for applications like detecting brain disorders, monitoring anesthesia depth, assessing driver fatigue, and identifying mental states - demonstrating its significance for clinical and biomedical applications.
3
This document provides an overview of magnetic resonance spectroscopy (MRS) and its application in Alzheimer's disease research. MRS is a noninvasive imaging technique that can measure the chemical composition of tissues in vivo and characterize metabolic processes. When combined with magnetic resonance imaging (MRI), MRS provides both anatomical and biochemical information. MRS detects biochemical alterations associated with disease pathophysiology. The document describes the basic physics of MRS and reviews its use in studying Alzheimer's disease, including quantifying neuronal damage and changes in neurochemical markers like N-acetyl aspartate.
In this paper we present the use of a signal processing technique to find dominant channels in
near infrared spectroscopy (NIRS). Cross correlation is computed to compare measuring
channels and identify delays among the channels. In addition, visual inspection was used to
detect potential dominant channels. The results showed that the visual analysis exposed painrelated
activations in the primary somatosensory cortex (S1) after stimulation which is
consistent with similar studies and the cross correlation analysis found dominant channels on
both cerebral hemispheres. The analysis also showed a relationship between dominant channels
and neighbouring channels. Therefore, our results present a new method to detect dominant
regions in the cerebral cortex using near-infrared spectroscopy. These results have also
implications in the reduction of number of channels by eliminating irrelevant channels for the
experiment.
CROSS CORRELATION ANALYSIS OF MULTI-CHANNEL NEAR INFRARED SPECTROSCOPYcscpconf
In this paper we present the use of a signal processing technique to find dominant channels in near infrared spectroscopy (NIRS). Cross correlation is computed to compare measuring channels and identify delays among the channels. In addition, visual inspection was used to detect potential dominant channels. The results showed that the visual analysis exposed painrelated activations in the primary somatosensory cortex (S1) after stimulation which is consistent with similar studies and the cross correlation analysis found dominant channels on both cerebral hemispheres. The analysis also showed a relationship between dominant channels
and neighbouring channels. Therefore, our results present a new method to detect dominant regions in the cerebral cortex using near-infrared spectroscopy. These results have also implications in the reduction of number of channels by eliminating irrelevant channels for the experiment.
CROSS CORRELATION ANALYSIS OF MULTI-CHANNEL NEAR INFRARED SPECTROSCOPYcscpconf
In this paper we present the use of a signal processing technique to find dominant channels in near infrared spectroscopy (NIRS). Cross correlation is computed to compare measuring channels and identify delays among the channels. In addition, visual inspection was used to detect potential dominant channels. The results showed that the visual analysis exposed painrelated activations in the primary somatosensory cortex (S1) after stimulation which is consistent with similar studies and the cross correlation analysis found dominant channels on both cerebral hemispheres. The analysis also showed a relationship between dominant channels and neighbouring channels. Therefore, our results present a new method to detect dominant regions in the cerebral cortex using near-infrared spectroscopy. These results have also implications in the reduction of number of channels by eliminating irrelevant channels for the experiment
Introducing Milvus Lite: Easy-to-Install, Easy-to-Use vector database for you...Zilliz
Join us to introduce Milvus Lite, a vector database that can run on notebooks and laptops, share the same API with Milvus, and integrate with every popular GenAI framework. This webinar is perfect for developers seeking easy-to-use, well-integrated vector databases for their GenAI apps.
GraphSummit Singapore | The Art of the Possible with Graph - Q2 2024Neo4j
Neha Bajwa, Vice President of Product Marketing, Neo4j
Join us as we explore breakthrough innovations enabled by interconnected data and AI. Discover firsthand how organizations use relationships in data to uncover contextual insights and solve our most pressing challenges – from optimizing supply chains, detecting fraud, and improving customer experiences to accelerating drug discoveries.
Enchancing adoption of Open Source Libraries. A case study on Albumentations.AIVladimir Iglovikov, Ph.D.
Presented by Vladimir Iglovikov:
- https://www.linkedin.com/in/iglovikov/
- https://x.com/viglovikov
- https://www.instagram.com/ternaus/
This presentation delves into the journey of Albumentations.ai, a highly successful open-source library for data augmentation.
Created out of a necessity for superior performance in Kaggle competitions, Albumentations has grown to become a widely used tool among data scientists and machine learning practitioners.
This case study covers various aspects, including:
People: The contributors and community that have supported Albumentations.
Metrics: The success indicators such as downloads, daily active users, GitHub stars, and financial contributions.
Challenges: The hurdles in monetizing open-source projects and measuring user engagement.
Development Practices: Best practices for creating, maintaining, and scaling open-source libraries, including code hygiene, CI/CD, and fast iteration.
Community Building: Strategies for making adoption easy, iterating quickly, and fostering a vibrant, engaged community.
Marketing: Both online and offline marketing tactics, focusing on real, impactful interactions and collaborations.
Mental Health: Maintaining balance and not feeling pressured by user demands.
Key insights include the importance of automation, making the adoption process seamless, and leveraging offline interactions for marketing. The presentation also emphasizes the need for continuous small improvements and building a friendly, inclusive community that contributes to the project's growth.
Vladimir Iglovikov brings his extensive experience as a Kaggle Grandmaster, ex-Staff ML Engineer at Lyft, sharing valuable lessons and practical advice for anyone looking to enhance the adoption of their open-source projects.
Explore more about Albumentations and join the community at:
GitHub: https://github.com/albumentations-team/albumentations
Website: https://albumentations.ai/
LinkedIn: https://www.linkedin.com/company/100504475
Twitter: https://x.com/albumentations
Cosa hanno in comune un mattoncino Lego e la backdoor XZ?Speck&Tech
ABSTRACT: A prima vista, un mattoncino Lego e la backdoor XZ potrebbero avere in comune il fatto di essere entrambi blocchi di costruzione, o dipendenze di progetti creativi e software. La realtà è che un mattoncino Lego e il caso della backdoor XZ hanno molto di più di tutto ciò in comune.
Partecipate alla presentazione per immergervi in una storia di interoperabilità, standard e formati aperti, per poi discutere del ruolo importante che i contributori hanno in una comunità open source sostenibile.
BIO: Sostenitrice del software libero e dei formati standard e aperti. È stata un membro attivo dei progetti Fedora e openSUSE e ha co-fondato l'Associazione LibreItalia dove è stata coinvolta in diversi eventi, migrazioni e formazione relativi a LibreOffice. In precedenza ha lavorato a migrazioni e corsi di formazione su LibreOffice per diverse amministrazioni pubbliche e privati. Da gennaio 2020 lavora in SUSE come Software Release Engineer per Uyuni e SUSE Manager e quando non segue la sua passione per i computer e per Geeko coltiva la sua curiosità per l'astronomia (da cui deriva il suo nickname deneb_alpha).
GraphSummit Singapore | The Future of Agility: Supercharging Digital Transfor...Neo4j
Leonard Jayamohan, Partner & Generative AI Lead, Deloitte
This keynote will reveal how Deloitte leverages Neo4j’s graph power for groundbreaking digital twin solutions, achieving a staggering 100x performance boost. Discover the essential role knowledge graphs play in successful generative AI implementations. Plus, get an exclusive look at an innovative Neo4j + Generative AI solution Deloitte is developing in-house.
Pushing the limits of ePRTC: 100ns holdover for 100 daysAdtran
At WSTS 2024, Alon Stern explored the topic of parametric holdover and explained how recent research findings can be implemented in real-world PNT networks to achieve 100 nanoseconds of accuracy for up to 100 days.
UiPath Test Automation using UiPath Test Suite series, part 6DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 6. In this session, we will cover Test Automation with generative AI and Open AI.
UiPath Test Automation with generative AI and Open AI webinar offers an in-depth exploration of leveraging cutting-edge technologies for test automation within the UiPath platform. Attendees will delve into the integration of generative AI, a test automation solution, with Open AI advanced natural language processing capabilities.
Throughout the session, participants will discover how this synergy empowers testers to automate repetitive tasks, enhance testing accuracy, and expedite the software testing life cycle. Topics covered include the seamless integration process, practical use cases, and the benefits of harnessing AI-driven automation for UiPath testing initiatives. By attending this webinar, testers, and automation professionals can gain valuable insights into harnessing the power of AI to optimize their test automation workflows within the UiPath ecosystem, ultimately driving efficiency and quality in software development processes.
What will you get from this session?
1. Insights into integrating generative AI.
2. Understanding how this integration enhances test automation within the UiPath platform
3. Practical demonstrations
4. Exploration of real-world use cases illustrating the benefits of AI-driven test automation for UiPath
Topics covered:
What is generative AI
Test Automation with generative AI and Open AI.
UiPath integration with generative AI
Speaker:
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
Dr. Sean Tan, Head of Data Science, Changi Airport Group
Discover how Changi Airport Group (CAG) leverages graph technologies and generative AI to revolutionize their search capabilities. This session delves into the unique search needs of CAG’s diverse passengers and customers, showcasing how graph data structures enhance the accuracy and relevance of AI-generated search results, mitigating the risk of “hallucinations” and improving the overall customer journey.
For the full video of this presentation, please visit: https://www.edge-ai-vision.com/2024/06/building-and-scaling-ai-applications-with-the-nx-ai-manager-a-presentation-from-network-optix/
Robin van Emden, Senior Director of Data Science at Network Optix, presents the “Building and Scaling AI Applications with the Nx AI Manager,” tutorial at the May 2024 Embedded Vision Summit.
In this presentation, van Emden covers the basics of scaling edge AI solutions using the Nx tool kit. He emphasizes the process of developing AI models and deploying them globally. He also showcases the conversion of AI models and the creation of effective edge AI pipelines, with a focus on pre-processing, model conversion, selecting the appropriate inference engine for the target hardware and post-processing.
van Emden shows how Nx can simplify the developer’s life and facilitate a rapid transition from concept to production-ready applications.He provides valuable insights into developing scalable and efficient edge AI solutions, with a strong focus on practical implementation.
Sudheer Mechineni, Head of Application Frameworks, Standard Chartered Bank
Discover how Standard Chartered Bank harnessed the power of Neo4j to transform complex data access challenges into a dynamic, scalable graph database solution. This keynote will cover their journey from initial adoption to deploying a fully automated, enterprise-grade causal cluster, highlighting key strategies for modelling organisational changes and ensuring robust disaster recovery. Learn how these innovations have not only enhanced Standard Chartered Bank’s data infrastructure but also positioned them as pioneers in the banking sector’s adoption of graph technology.
Alt. GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using ...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
Full-RAG: A modern architecture for hyper-personalizationZilliz
Mike Del Balso, CEO & Co-Founder at Tecton, presents "Full RAG," a novel approach to AI recommendation systems, aiming to push beyond the limitations of traditional models through a deep integration of contextual insights and real-time data, leveraging the Retrieval-Augmented Generation architecture. This talk will outline Full RAG's potential to significantly enhance personalization, address engineering challenges such as data management and model training, and introduce data enrichment with reranking as a key solution. Attendees will gain crucial insights into the importance of hyperpersonalization in AI, the capabilities of Full RAG for advanced personalization, and strategies for managing complex data integrations for deploying cutting-edge AI solutions.
In his public lecture, Christian Timmerer provides insights into the fascinating history of video streaming, starting from its humble beginnings before YouTube to the groundbreaking technologies that now dominate platforms like Netflix and ORF ON. Timmerer also presents provocative contributions of his own that have significantly influenced the industry. He concludes by looking at future challenges and invites the audience to join in a discussion.
Observability Concepts EVERY Developer Should Know -- DeveloperWeek Europe.pdfPaige Cruz
Monitoring and observability aren’t traditionally found in software curriculums and many of us cobble this knowledge together from whatever vendor or ecosystem we were first introduced to and whatever is a part of your current company’s observability stack.
While the dev and ops silo continues to crumble….many organizations still relegate monitoring & observability as the purview of ops, infra and SRE teams. This is a mistake - achieving a highly observable system requires collaboration up and down the stack.
I, a former op, would like to extend an invitation to all application developers to join the observability party will share these foundational concepts to build on:
Observability Concepts EVERY Developer Should Know -- DeveloperWeek Europe.pdf
Mottin laporte-cespuglio-2003
1. Journal of Neurochemistry, 2003 10.1046/j.0022-3042.2003.01508.x
Inhibition of NADH oxidation by chloramphenicol
in the freely moving rat measured by picosecond
time-resolved emission spectroscopy
Stephane Mottin,* Pierre Laporte* and Raymond Cespuglio
´
*LTSI, CNRS UMR 5516, University of St-Etienne, St-Etienne, France
INSERM U480, University of Lyon, Lyon, France
Abstract implies an efficient inhibition of complex I of the respiratory
Owing to the lack of methods capable to monitor the energetic chain by CAP. It refers to the mechanism through which the
processes taking place within small brain regions (i.e. nucleus adverse effects of the antibiotic may take place. It could explain
raphe dorsalis, nRD), the neurotoxicity of various categories of why paradoxical sleep, a state needing aerobic energy to
substances, including antibiotics and psycho-active drugs, still occur, is suppressed after CAP administration. The present
remains difficult to evaluate. Using an in vivo picosecond approach constitutes the first attempt to determine by fluor-
optical spectroscopy imaging method, we report that escence methods the effects of substances on deep brain
chloramphenicol (CAP), besides its well-known ability to inhibit structures of the freely moving animal. It points out that in vivo
the mitochondria protein synthesis, also influences the NADH/ ultrafast optical methods are innovative and adequate tools for
NAD+ redox processes of the respiratory chain. At a 200-mg/kg combined neurochemical and behavioural approaches.
dose, CAP indeed produces a marked increase in the fluor- Keywords: antibiotic, behaving rat, NADH, neurotoxicity,
escent signal of the nRD which, according to clear evidence, is sleep, time-resolved fluorescence.
likely to be related to the NADH concentration. This effect also J. Neurochem. (2003) 10.1046/j.0022-3042.2003.01508.x
To date, the ÔseasonedÕ chloramphenicol (CAP) antibiotic still regard to mitochondria metabolism. However, approaches
remains widely used in developing countries (Kumana et al. related to the in vivo study of the brain mitochondria
1993) and the importance of its supply is so crucial that it networks (Glinka et al. 1998; Yaffe 1999) still remain
often leads to forgery (Payet 1997). This substance, among difficult. Owing to the progress of neurophotonics, direct
the most famous mitochondriotropic drugs used in research brain investigations have been started in the unanesthetized
(Kroon and Arendzen 1972; Yunis 1988; Bories and Cravendi animal (Mottin et al. 1997; Cassarino and Bennet 1999).
1994) is obviously precious in the case of serious epidemic Besides, it is also known that mitochondria are elements
(Niel et al. 1997) and of multiresistant treatments (Barie sensitive to antibiotics (Ramilo et al. 1988; Snavely and
1998). Owing to its excellent accessibility to the cerebro- Hodges 1984; Degli Esposti 1998) and, in this respect, CAP
spinal fluid and brain tissue, this antibiotic is incomparably has been widely studied. After discovery of the CAP ability
efficient against meningitis and typhoid fever (Meulemans to inhibit mitochondria respiratory processes (Stoner et al.
et al. 1986). Nevertheless, it must be mentioned that its 1964), several other reports (Freeman and Haldar 1967;
administration to patients often induces adverse effects Freeman and Haldar 1968; Freeman and Haldar 1970; Kroon
including mental confusion, headache, appetite loss, oph-
talmoplegia, selective inhibition of paradoxical sleep (PS) and Received March 5, 2002; revised manuscript received July 15, 2002;
epileptogenic manifestations (Abou-Khalil et al. 1980; Yunis accepted October 7, 2002.
1988; Holt et al. 1993; Bories and Cravendi 1994). Address correspondence and reprint requests to Stephane Mottin,
´
Most of the antibiotic adverse effects on the brain have LTSI, CNRS UMR 5516, F-42023 St-Etienne Cedex 02, France.
E-mail: MOTTIN@univ-st-etienne.fr
often been misinterpreted (Snavely and Hodges 1984; Abbreviations used: CAP, chloramphenicol; Cx, cortex; 5HT,
Thomas 1994; Norrby 1996; Kanemitsu and Shimada 5-hydroxytryptamine; i.p., intraperitoneal; nRD, nucleus raphe dorsalis;
1999). As yet, many CAP metabolites have been studied in ps, paradoxical sleep; TRES, time-resolved emission spectroscopy.
Ó 2003 International Society for Neurochemistry, J. Neurochem. (2003) 10.1046/j.0022-3042.2003.01508.x 1
2. 2 S. Mottin et al.
and Arendzen 1972; Abou-Khalil et al. 1980) further pointed with a special VUV window (StreakScope from Hamamatsu, Japan)
out that this compound is an inhibitor of the mitochondria and a 270-M spectrograph (Spex Jobin-Yvon, France) were also
complex I (NADH-ubiquinone oxidoreductase, EC 1.6.5.3) used in the second generation of the optical design. Images obtained
on isolated mitochondria preparations. They allowed the with the streak camera were registered through a two-dimensional
single-photon counting mode (Watanabe et al. 1994).
conclusion that the concentration of CAP necessary for the
inhibition of complex I is far superior to the concentration
TRES methodology in vivo
necessary for the mitochondria protein synthesis inhibition. When the measurements are limited in intensity, without a real-time
Since this period, CAP has been used, even in vivo, as a TRES analysis, the link existing between the photo-electron counts
ÔpureÕ mitochondria protein synthesis inhibitor. Its ability to and the fluorophore concentration variation cannot be defined
inhibit the mitochondria complex I has been neglected since (Mottin et al. 1993). The optical signal is proportional to the NADH
considered as effective only in vitro at strong overdoses concentration variation only if the spectrum and the decay-time
(Abou-Khalil et al. 1980; Yunis 1988; Holt et al. 1993; remain unchanged. Thus, if the NADH quantum efficiency changes,
Bories and Cravendi 1994). CAP presents, nevertheless, an if another emission overlaps the NADH fluorescence or if the inner
unusual excellent accessibility to the cerebro-spinal fluid and filters absorb NADH emission, then the conventional fluorimetric
brain tissue where its accumulation may reach a concentra- methods fail. TRES imagery avoids these inconveniences and
allows a more objective analysis of tissue optics. In order to add
tion efficient enough to inhibit mitochondria respiration
strength to our methodology, we also introduced the control of the
(Meulemans et al. 1986).
photon counting rate. For this purpose, the laser intensity was set at
Throughout this report, we provide answers to the a low level: 0.15 mW, 30 Hz, 5 lJ/pulse. The excitation wave-
unsolved problems attached to the adverse effects of CAP lengths were (i) 337 nm, with a nitrogen laser at a repetition rate of
not related to the inhibition of mitochondria protein synthe- 30 Hz and a FWHM (full width at half max) of 300 ps (LN 100,
sis. For this purpose, NADH/NAD+ redox processes taking Laser Photonics, USA) and (ii) 355 nm with a tripled YAG laser at a
place in the nucleus raphe dorsalis (nRD) of the freely repetition rate of 30 Hz and a FWHM of 3.5 ns (OPO901,
moving rat were first monitored with a picosecond time- BMIndustrie, France). Despite this long FWHM, the 355 nm
resolved fluorescence method. The nRD target was chosen wavelength was of a great interest with regard to the recent
because of its involvement in sleep triggering (Cespuglio picosecond YAG microchip laser developments. For the 337 and
et al. 1992) and CAP was employed on the basis of its ability 355 nm wavelengths, we used a time window of 10 ns and 20 ns,
respectively, the integration time being set at one minute. In the
to suppress PS (Petitjean et al. 1979). Afterwards, the effect
487–508 nm emission wavelength window, the magnitude of the
of CAP on the NADH/NAD+ redox balance was checked.
noise (measured in deionized water) was 2% and 8.5% of the basal
nRD fluorescent signal for 337 and 335 excitation wavelengths,
respectively.
Materials and methods Significance of the increase in fluorescence observed after CAP
administration can be analysed in using different statistical tests. As
Experimental procedure our in vivo results are time series data we used a paired t-test well
In 15 OFA male rats (IFFA CREDO, France) weighing 280–300 g adapted to evaluate the significance of the changes observed.
and anaesthetised with chloral hydrate [400 mg/kg, intraperitoneal In pharmacology, temporal distributions of such time-dependent
(i.p.)], a guide canula was implanted in the nRD according to a variables are usually studied by non-linear regression analysis. Thus,
procedure previously described (Mottin et al. 1997). After 10 days in order to quantify all aspects of the mean increase in the
of recovery (12 h)12 h light/dark, temperature at 24 ± 0.5°C, food autofluorescence induced by CAP, a mathematical pharmacokinetic
and water ad libitum) time-resolved fluorescence measurements model was defined, i.e. y ¼ a + b {1 ) exp[– (t ) d )/c]}, y being
were carried out (daily sessions of 4–8 h). At the end of the the value of the fluorescent signal expressed in single photo-electron
experimental sessions, the animals were killed with a lethal dose of count units (SPE) and t the temporal scale in minutes. Coefficients a,
nembutal and the position of the working sensor checked. CAP b, c and d represent, respectively, the basic autofluorescence level
hemisuccinate (SolnicolÓ, Synthelabo, France) and saline solution (in SPE count), its increase (in SPE count), the time lapse covering
were administered i.p. For the 337 nm excitation wavelength this variation (min) and the delay (min) existing between the
experiments, two CAP doses were used, i.e. 200 and 400 mg/kg. injection procedure and the beginning of the signal increase. To
With the 355 nm excitation wavelength, experiments were conduc- assess the validity of the model, the regression coefficient (R), was
ted with a 300-mg/kg dose. always set above 0.95.
Time-resolved emission spectroscopy (TRES)
An application of ultrafast neurophotonics enabling both spectral
Results
and temporal analysis of tissue fluorescence in behaving animals has
been achieved in this study. The first generation of the set-up used
was described before (Mottin et al. 1997). Briefly, delivery and TRES imagery in vivo
collection of the optical signals (laser excitation and emission) were A typical TRES image, derived from the nRD, is illustrated
performed through a thin optical fibre allowing a good anatomical in Fig. 1(a). The autofluorescence spectrum is measured in
resolution (core diameter ¼ 200 lm). A streak camera equipped the 377–554 nm window (Fig. 1b). The temporal analysis of
Ó 2003 International Society for Neurochemistry, J. Neurochem. (2003) 10.1046/j.0022-3042.2003.01508.x
3. Inhibition of NADH oxidation by chloramphenicol 3
Fig. 1 (a) Typical time-resolved spectroscopy image derived from the number of SPE counts for each pixel. The black part corresponds to
nucleus raphe dorsalis (nRD) by using a two-dimensional single photo- zero SPE, the white part to 1 SPE. Grey becomes darker throughout
electron (SPE) counting. The spectrum of the autofluorescence is the SPE counting. A rapid variation occurs from 1 to 10 SPE counting.
shown in (b). (c) shows the temporal shape corresponding to the This image was acquired over 15 min.
spectral window 487–508 nm. The colours of the z-axis give the
the fluorescence shape gives a mean decay time of counting rate was lower for the 337 nm wavelength excita-
900 ± 50 ps within the 487–508 nm window (Fig. 1c). tion than for the 355 nm one. This was mainly due to the
difference in the laser beam quality and the coupling into the
Changes induced by CAP optical fibre.
In freely moving animals, saline administration did not The mean values of (c) also given ± the standard error are,
induce behavioural changes nor variations in the TRES respectively, for 200 mg/kg, 300 mg/kg and 400 mg/kg:
signal. However, all the i.p. injections of CAP succinate 71 ± 33 min, 107 ± 24 min and 126 ± 35 min.
(200–400 mg/kg) performed in the same conditions induced The delay (d ) existing between the injection proce-
a highly significant increase in the nRD blue fluorescence dure and the beginning of the signal increase is in a
(Fig. 2). The mean values of the basal counting (a) given ± the 2–14 min time window with a mean peaking at 4 min. The
standard error are, respectively, for 200 mg/kg, 300 mg/kg fluorescence increment (b) induced by CAP injection is
and 400 mg/kg: 12721 ± 2310 SPE, 48794 ± 2474 SPE and shown on Fig. 3. The paired t-test comparisons performed
16013 ± 1051 SPE. We further noticed that the basal indicate that the differences existing between the CAP doses
Ó 2003 International Society for Neurochemistry, J. Neurochem. (2003) 10.1046/j.0022-3042.2003.01508.x
4. 4 S. Mottin et al.
Fig. 4 In vivo fluorescence spectra derived from the nRD and induced
by a nitrogen laser excitation. Each spectrum is the mean of seven
spectra measured about 30 min before injection.
are significant. The differences existing between the CAP
doses between 200 mg/kg and 300 mg/kg are significant.
Between 300 mg/kg and 400 mg/kg or between 200 mg/kg
and 400 mg/kg the differences are highly significant.
Regarding the 337 nm excitation, spectra obtained before
CAP injection exhibited a high variability in the UV-purple
part. Below 450 nm, several patterns of the spectra and decay
times were also measured. This variability might be due to the
presence or the absence of a UV-purple shoulder coming
probably from different endogeneous fluorophores also com-
bined with the Soret band of the haemoglobins (inner effect).
Concerning again the above variability, the 450–480 nm
window was in an intermediate position while above 480 nm,
the UV-purple shoulder was less sensitive (Fig. 4).
In the case of the 355 nm excitation, basal spectra were
Fig. 2 Time-resolved spectroscopic measurements achieved in the more reproducible. Figure 5 illustrates the variations induced
nRD. (a), (b) and (c) are, respectively, devoted to the 200 mg/kg, by a CAP injection on the whole spectral window. In the
400 mg/kg and 300 mg/kg dose. Each point represents the sum of
450–550 nm window, the increase in fluorescence obtained
single photo-electron counts performed in time-resolved emission
was greater than in the 380–440 nm window (four positive
spectroscopy within the nRD (windows: 488–507 nm). The pharma-
effects/five trials).
cokinetic exponential fitting y ¼ a + b{1 ) exp[– (t ) d )/c]} is shown.
Some data are missing due to data processing and the back-up pro-
Finally, we also checked that, for a 300-mg/kg dose of
cedure. Symbols are used for clarity. CAP, the overall CAP pharmacokinetics (increase and
decrease down to the basic fluorescence level) occurred
within 6–7 h.
Changes induced by the animal death
Concerning the ability of CAP (or metabolites) to inhibit the
NADH/NAD+ redox processes of the respiratory chain in
the nRD, it is hard to give an absolute evaluation of the
inhibition strength. In order to overcome this difficulty, we
compared the changes occurring in the signal during the
animal death (lethal dose of barbiturates: 120 mg/kg) with
those obtained after a CAP injection. The lethal dose was
used when the basal level fluorescent signal before CAP
Fig. 3 The mean NADH fluorescence increment induced by CAP
injection was fully reached. Results obtained indicate that
injections is quantified by (b). A paired t-test comparison indicates that during death the increase in the fluorescent signal is faster
significant differences exist between the CAP doses (between 200 and and higher than after a CAP dose of 300 mg/kg (Fig. 6). The
300 mg/kg; between 300 and 400 mg/kg and between 200 and magnitude of the NADH fluorescence increase induced by
400 mg/kg). the CAP is close to 40% of the death effect.
Ó 2003 International Society for Neurochemistry, J. Neurochem. (2003) 10.1046/j.0022-3042.2003.01508.x
5. Inhibition of NADH oxidation by chloramphenicol 5
Fig. 5 In vivo fluorescence spectra derived from the nRD and induced
by a 355-nm excitation. Each spectrum is the mean of seven spectra
measured about 30 min ÔbeforeÕ or 115–125 min ÔafterÕ injection of
CAP. The curves are marked by symbols which correspond to the
symbols of the Fig. 2(c). The ratio (the spectrum ÔafterÕ divided by the
spectrum ÔbeforeÕ) is indicated for each curve.
Ó 2003 International Society for Neurochemistry, J. Neurochem. (2003) 10.1046/j.0022-3042.2003.01508.x
6. 6 S. Mottin et al.
occurs at 278 nm. Within the large 320–600 nm wavelength
window, the CAP and metabolites absorption (Bories and
Cravendi 1994) are thus negligible. Therefore, the optical
properties of CAP and metabolites cannot interfere with the
signal measured.
For the optical properties of the brain tissue, some
modifications may occur when CAP is strongly infused
intravenously (Sangiah and Burrows 1989). In such condi-
tions, hypotension is triggered together with an increase in
Fig. 6 Events related to a CAP injection (a) or to the animal death the cerebral blood volume. Both events could well be at the
(b). In the case illustrated in (b), the animal was killed (lethal dose basis of a haemodynamic artefact. Regarding this aspect, we
of barbiturates, i.e. 120 mg/2 mL for the entire animal) 8 h after a emphasize that our experimental protocol used only i.p.
300-mg/kg i.p. injection of CAP succinate (the c coefficient is administrations of CAP and that our methodological set-up
3.8 ± 0.5 min). The basal level of the signal is fully reached 7 h after
exhibited a photon counting rate in the same range through-
the 300 mg/kg i.p. injection. The nRD fluorescence was measured at
out the different experimental sessions. This homogeneity
355 nm excitation wavelength (emission wavelength 484–508 nm).
underlines that our sensor was at a scale avoiding angioar-
chitectonic influences of the nRD. This nucleus is, indeed,
poorly vascularized (Descarries et al. 1982) as about 12–24
Discussion
capillary lumens are present in the section of our sensor. In
Data obtained indicate that CAP induces a significant the 480–540 nm window, however, the tissue absorption is
increase in the laser (335–337 nm excitation wavelengths) lower than in UV and might increase the absorption and the
induced NADH fluorescent signal of the nRD. For a CAP scattering effects produced by the nRD capillaries. Despite
dose of 300 mg/kg the effect obtained is close to 40% of the this assumption, we nevertheless observed that the 480–
death triggered variation. 540 nm spectral shapes do not change after CAP adminis-
tration. Whatever the complexity of the optical tissue
NADH dependence of the fluorescent signal properties might be, the time-course of the transient hypo-
Since the pioneering work of Chance et al. (1962), several tension attached to CAP administration is inferior to 10 min
optical designs have been published (Mottin et al. 1997). (Sangiah and Burrows 1989) and cannot in itself explain the
Many authors discussed the link existing between the UV- exponential increase observed in the fluorescent signal over
induced brain fluorescence and the NADH intramitochondria 2 h. Moreover, we underline that the design of the monofibre
concentration (Rex et al. 1999; Sick and Perez-Pinzon 1999; sensor employed: (i) limits the number of scattering events;
Hashimoto et al. 2000; Schuchmann et al. 2001). Again, the and (ii) allows a probing in small volumes as well as the
recent and important changes reported in the mitochondria largest collection of photons. This sensor design further
glucose-stimulated NADH fluorescence from intact pancre- avoids the geometrical blindness of a multioptic fibre
atic islets (Eto et al. 1999; Patterson et al. 2000) confirm this configuration in scattering media.
aspect. It is thus very likely that the brain autofluorescence Concerning the changes occurring in the quantum effi-
measured in the 480–540 nm window might be attached to ciency of the fluorophores, the fluorescence decay time
NADH (for 337 or 355 nm excitation wavelengths). How- analysis performed is well suited. Indeed, in vitro, the
ever, since the TRES imagery, used in the present approach, quantum efficiencies of either free or protein-bound forms of
offers, over conventional spectrofluorimetric methods, the NADH exhibit decay time variations in a range running from
beneficial access to a complete analysis of the tissue 0.3 ns to 4 ns (Ross et al. 1982). In vivo, however, we have
fluorescence, we again considered the dependence of the not observed significant variations in the temporal shape of
fluorescent signal measured on the NADH concentration. In the fluorescence in the 480–540 nm window. Thus, the
this respect, we further analysed whether the signal obtained increase in the nRD fluorescence obtained after CAP
could be produced by CAP itself. In the 480–540 nm injection is not dependent on the changes occurring in the
window, the changes observed might indeed result not only quantum efficiency. It might thus be directly linked with
from an increase in the NADH concentration, but also from: NADH concentration changes and complex I inhibition.
(i) the optical properties of xenobiotic compounds; (ii) the
modifications occurring in the optical properties of the tissue; Death versus CAP effect
and (iii) the increase in quantum efficiency of endogenous It is clear that the increase in fluorescence induced by death
fluorophores. cannot be used directly as a perfect anoxic test of reference
Regarding the optical properties of xenobiotic compounds, since its amplitude depends on the nature of the anaesthetic
it can be underlined that the first spectral component (Holt et al. 1993; Bories and Cravendi 1994) and the
observed in UV absorption, with CAP in water at pH 7, concomitant transient modifications occurring in the optical
Ó 2003 International Society for Neurochemistry, J. Neurochem. (2003) 10.1046/j.0022-3042.2003.01508.x
7. Inhibition of NADH oxidation by chloramphenicol 7
properties of the tissue (Delpy et al. 1988). Whatever these might contribute to the CAP effect reported here. Thus, our
inconveniences might be, when death occurs, mitochondria in vivo results raise once more the question related to the
redox processes are totally suppressed and NADH remains CAP toxicity. In this respect, several studies (Freeman and
fully reduced. If the strength of this inhibition is referenced at Haldar 1968; Freeman and Haldar 1970; Abou-Khalil et al.
100%, then the in vivo effect obtained with CAP reaches 1980; Glazko 1987; Yunis 1988; Holt et al. 1993; Bories and
40% of the death-related changes. To fulfil this aspect from Cravendi 1994) have already suggested that the p-NO2 group
an experimental point of view, the use of different inhibitors may be related to the complex I inhibition. This is also
of the complex I, for example, rotenone (Degli Esposti supported by the fact that thiamphenicol (TAP), differing
1998), would be useful. Finally, if we assume that the from CAP by a methylsulfonyl moiety replacing the p-NO2
maximal level of the NADH fluorescence occurs after death, group, is inactive on complex I (Freeman and Haldar 1968;
the complex I inhibition could be estimated around 40% for a Freeman and Haldar 1970; Abou-Khalil et al. 1980). TAP
300-mg/kg CAP injection. As discussed above, if the optical remains, however, capable to induce an inhibition of the
properties of CAP and metabolites cannot not interfere protein synthesis like CAP. In this sense, our preliminary
directly with the signal measured, the inhibition of the results (not shown) indicate that in vivo TAP does not
complex I could come from CAP itself or some of its increase the brain autofluorescence.
metabolites.
Does the complex I inhibition achieved by CAP occur
Is the complex I inhibition induced by CAP in preferential neuronal sets?
or by some of its p-NO2 metabolites? The complex I appears to be concentrated in brain regions
CAP offers a unique example in terms of metabolic pathway containing a high density of excitatory synapses (Higgins
diversity (Glazko 1987; Bories and Cravendi 1994). It is and Greenamyre 1996). A preference for the dendrites (60%)
questioned here whether some of the CAP metabolites could has also been reported (Wong-Riley 1989; Higgins and
lead to the rise observed in the nRD NADH fluorescence Greenamyre 1996). The nRD area probed ((200 lm)3, about
after CAP administration. In this respect, CAP, poorly 200–300 nerve cell bodies) in our experiments exhibits
soluble in water, is often formulated as an biologically numerous dendrites (Descarries et al. 1982). The nRD
inactive ester. CAP succinate, however, is hydrolysed into comprises also the largest collection of 5HT cell bodies
the active form of CAP in the liver, lungs and kidneys. The (about 50% of the whole nerve cells) in rats (Descarries et al.
rate at which this hydrolysis occurs in the liver appears to be 1982), in cats (Chazal and Ralston 1987) and in humans
highly variable among individuals (Kroon and de Jong 1979) (Dorph-Petersen 1999). Finally, the area occupied by mito-
and this is confirmed and quantified by our data. The increase chondria (10%) was estimated nearly identical in 5HT and
in CAP concentration in brain tissue is a composite function non-5HT neurones (Descarries et al. 1982). Thus, the
of its hydrolysis rate, the excretion of CAP succinate, the complex I inhibition does not occur exclusively in 5HT
glucuronidization into CAP glucuronide and the blood–brain neurones.
barrier transfer. As the concentration of CAP into the
cerebro-spinal fluid of the rat injected with a 165-mg/kg dose Is the complex I inhibition tissue-specific in vivo?
is 23 ± 5 mg/L during the first hour postinjection (Meule- In in vitro preparations, the inhibition induced by CAP has
mans et al. 1986), in our experiments a 200-mg/kg dose been observed at doses 5–10-fold higher than those used in
might lead to a CAP concentration around 26–28 mg/L (80– our experiments (Stoner 1964; Freeman and Haldar 1967;
110 lM). Further, in in vitro mitochondria preparations, a Freeman and Haldar 1968; Freeman and Haldar 1970;
50% inhibition of the complex I is achieved by CAP in the Kroon and Arendzen 1972; Abou-Khalil et al. 1980; Yunis
400–1000 lM range (Freeman and Haldar 1968; Freeman 1988). Moreover, it was also shown that the CAP inhibition
and Haldar 1970; Kroon and Arendzen 1972; Abou-Khalil site fits in many aspects with that of rotenone (Freeman and
et al. 1980), while for oxidative phosphorylation a 7–17% Haldar 1970). CAP belongs indeed to a class of polycyclic
inhibition is obtained at 100 lM (Kroon and Arendzen 1972; hydrophobic inhibitors (rotenone-like) related to quinone.
Abou-Khalil et al. 1980). In our experimental conditions, the In vivo, the existence of brain complex I tissue-specific
nRD complex I inhibition might thus be in the above range. isoenzymes have been suggested as well as the fact that
It is not excluded, however, that the large NADH rise rotenone impairs more strongly the brain than skeletal
obtained after CAP administration could come from one of muscles, the heart and kidneys (Higgins and Greenamyre
its metabolites. The consistent investigations conducted as 1996). In this respect, a threshold effect has been proposed
yet on CAP metabolism (Abou-Khalil et al. 1980; Glazko as an additional mechanism contributing to the tissue
1987; Yunis 1988; Holt et al. 1993; Bories and Cravendi specificity suggested (Davey et al. 1998; Rossignol et al.
1994) point out nitroso-CAP (NO-CAP) as a putative 1999; Rossignol et al. 2000). The threshold value quantifies
candidate. Although not identified in clinical samples (Holt how far the enzymatic activity can be reduced before the
et al. 1993; Bories and Cravendi 1994), this compound occurrence of significant impairments of the oxidative
Ó 2003 International Society for Neurochemistry, J. Neurochem. (2003) 10.1046/j.0022-3042.2003.01508.x
8. 8 S. Mottin et al.
phosphorylation. Data reported indicate a strong tissue of a reduced production of energy in the areas where the
difference for the complex I, i.e. about 40–50% inhibition complex I threshold is exceeded. Finally, in practice, a cheap
leads to brain energy impairments while the threshold values mitochondria neuroprotective substance, given in association
are mean of 70–80% for the liver, the muscle, etc. with CAP, would protect patients against adverse effects of
(Rossignol et al. 1999; Rossignol et al. 2000). More the antibiotic in several underdeveloped countries.
detailed studies (Davey and Clark 1996; Davey et al.
1997; Davey et al. 1998) further specify that the low CAP and paradoxical sleep
threshold values differed among various brain regions The implications of our results extend beyond the field
(hippocampus, cortex) when considering non-synaptic related to the antibiotic neurotoxicity. In this respect, we
(60%) or synaptic mitochondria (25%). When the 25% recall that in 1974, in our laboratory, CAP was given orally,
threshold is exceeded, mitochondria respiration is severely as an antibiotic, to cats equipped only with the polygraphic
impaired, resulting in a reduced synthesis of ATP. Below this electrodes allowing the sleep-wake states scoring. A marked
threshold, the complex I activity changes and the proton- inhibition of PS occurrence was then noticed and later
electron fluxes remain nearly unchanged. But, this is not confirmed in mice and rats (Petitjean et al. 1979; Fride et al.
exactly the case for NADH since its variations are devoted 1989; Prospero-Garcia et al. 1993). Up to now, the mech-
to the maintenance of the fluxes at the same level. Moreover, anisms related to this effect have remained unexplained.
in in vivo situation, control of critical ratio (oxidative They have been, nevertheless, at the basis of a fruitful
phosphorylation fluxes/free radical production) and thresh- research on the nature of the link existing between protein
olds can also be influenced (Barrientos and Moraes 1999), synthesis and PS occurrence. But PS inhibition related to
for example by glutathione which reduces complex I CAP does not result from a specific inhibition of the protein
threshold (Davey et al. 1998). When the cellular redox state synthesis since TAP, a structural analogue of CAP achieving
is unbalanced, the redox centres produce more free radicals, the same protein synthesis inhibition, does not prevent PS
introducing the cell in a vicious cycle (Barrientos and occurrence (Petitjean et al. 1979; Fride et al. 1989; Prosper-
Moraes 1999) amplifying the reactive oxygen species fluxes o-Garcia et al. 1993). Afterwards, the possibility of a PS
with a high tissue susceptibility (Esposito et al. 1999). dependence on energetic metabolism emerged (Jouvet 1994;
Thus, the fact that very low doses of CAP are capable to Mottin et al. 1997). Data reported here fulfil the hypothesis
trigger the in vivo complex I inhibition might be related to: (i) that PS might indeed be energy-gated (Jouvet 1994). They
complex I specific steric factors towards rotenone binding underline that respiratory chain inhibition at the complex I
sites; (ii) very low threshold value of brain complex I; and level is a determinant event in the CAP-related PS suppres-
(iii) in vivo redox situation. sion.
In vivo CAP neurotoxicity
Conclusion
Concerning this aspect, it is likely that brain mitochondria
injury induced by CAP could result from inhibition of During the past 25 years, mitochondria complex I inhibition
complex I and protein synthesis. Our results do not imply by CAP has been considered to be sensitive only at strong
that the inhibition of the protein synthesis results secondarily overdoses. Our report shows that, in vivo, this inhibition is
from the complex I inhibition. They only suggest that these effective at clinical dosages of the substance. The CAP
two processes run in parallel when the CAP dose admin- neurotoxicity is, at least in part, a consequence of the complex
istered is sufficient enough for triggering both of them. Most I inhibition. This adverse property, limiting the oxidative
of the CAP side-effects reported in neurological practice production of ATP, might explain why PS, an energy-gated
might be the consequence of the brain complex I inhibition. state, is suppressed after the antibiotic administration. More-
CAP was used widely in paediatric practice until the over, the TRES optical methods appear to be well-suited for
identification of the so-called Ôgrey syndromeÕ in the late probing brain mitochondria functions in relation with beha-
1950s as a result of the antibiotic treatment. Despite viour. They can be also of paramount importance for studies
intensive research, the mechanism of the CAP-induced related to the brain toxicology of substances.
aplasia remain unexplained (Glazko 1987; Holt et al. 1993).
A tentative explanation could reside in the fact that in vivo,
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