The document discusses using neutrons for in-situ observation of engineering material behavior. It describes the ENGIN-X beamline at ISIS, which allows for various types of in-situ experiments including mechanical deformation, heat treatment, and phase transformations. Examples are given of experiments involving in-situ heat treatment, cyclic electric fields on ferroelectrics, welding, and fatigue crack growth. Practical considerations for in-situ neutron experiments and opportunities for future directions are also outlined.
Multi-channel Detector Readout Integrated Circuits with ADCs for X-ray and Ga...Gunnar Maehlum
We are developing detector readout integrated circuits (ROICs) for X-ray and Gamma-ray spectroscopy. The ROICs are applications specific (ASICs) for satellite instrumentation in space. The ICs described in this article belong to the VATA family with integrated analog-to-digital converters (ADCs) for fully digital readout of x-ray and gamma-ray detectors. The VATAs are ideal for the readout of cadmium zinc telluride (CZT), cadmium telluride (CdTe), silicon pads and strips, and large area avalanche photodiodes (APDs) with scintillators.
Passive millimeter wave imaging using subharmonic self-oscillating mixingSimone Angela Winkler
The usefulness of passive millimeter-wave imaging lies in particular in the peculiarities of atmospheric attenuation phenomenologies allowing millimetre-waves to penetrate through a variety of low-visibility conditions such as haze, fog, clouds, smoke, and sandstorms and furthermore in the ability to propagate through clothing and a number of other materials. Present and future applications consist in both military and
commercial infrastructure fields such as in surveillance, navigation, and automotive technology, security screening systems, and biomedical imaging. My work in this field focused on the development of novel types of receivers using self-oscillating mixing technology based on nonlinear subharmonic principles.
Multi-channel Detector Readout Integrated Circuits with ADCs for X-ray and Ga...Gunnar Maehlum
We are developing detector readout integrated circuits (ROICs) for X-ray and Gamma-ray spectroscopy. The ROICs are applications specific (ASICs) for satellite instrumentation in space. The ICs described in this article belong to the VATA family with integrated analog-to-digital converters (ADCs) for fully digital readout of x-ray and gamma-ray detectors. The VATAs are ideal for the readout of cadmium zinc telluride (CZT), cadmium telluride (CdTe), silicon pads and strips, and large area avalanche photodiodes (APDs) with scintillators.
Passive millimeter wave imaging using subharmonic self-oscillating mixingSimone Angela Winkler
The usefulness of passive millimeter-wave imaging lies in particular in the peculiarities of atmospheric attenuation phenomenologies allowing millimetre-waves to penetrate through a variety of low-visibility conditions such as haze, fog, clouds, smoke, and sandstorms and furthermore in the ability to propagate through clothing and a number of other materials. Present and future applications consist in both military and
commercial infrastructure fields such as in surveillance, navigation, and automotive technology, security screening systems, and biomedical imaging. My work in this field focused on the development of novel types of receivers using self-oscillating mixing technology based on nonlinear subharmonic principles.
IMU (inertial measurement unit) has already played significant roles in the control system of aerospace and other vehicle platforms. Due to the maturity and low cost of MEMS technology, IMU starts to penetrate consumer products such as smartphone, wearables and VR/AR devices.
This sharing will focus on the general introduction of IMU components, signal characteristics and application concepts, with an attempt to guide those who is interested in the IMU-based system integration and algorithm development.
CLEO 2009: High Frequency Polarization Switching VCSEL Clock Using Subwavelength Quarter-Wave Plate
by:
Clinton J. Smith, Wen-Di Li, Shufeng Bai, and Stephen Y. Chou
Copper (775) - an optics, 2PPE, and Bulk state simulation studyPo-Chun Yeh
My earlier studies on Cu(775) - a tilt cut highly crystalline copper surface using ultrafast femtosecond laser based 2-photon photoemission and its related simulation via Fortran 77.
This project targets the development of novel pocket X-ray sources and X-ray direct detectors that will be combined in a distributed network to solve important tasks, for example in the field of security, by ensuring reliable and real-time monitoring of failure sensitive parts in large manufacturing plants or in public transportation.
The miniaturized X-ray sources are based on multi-wall carbon nanotube (CNT) cold electron emitters and advanced microsystems technology. The electron field emission properties of CNTs, with their high current densities, make them prime candidates for cold emitter cathodes. Using CNT cold electron emitters will make it possible to miniaturize the whole X-ray source. Additionally, as opposed to classical thermionic emission, field electron emission of the CNT is voltage-controlled which allows for high modulation frequencies up to GHz level. The X-ray direct detectors in turn are based on crystalline germanium absorption layers grown directly on a CMOS sensor chip yielding high resolution and high sensitivity X-ray detectors. Single photon detection will allow for a significant improvement of contrast for applications in security, health care and nondestructive testing.
Kilohertz-Rate MeV Ultrafast Electron Diffraction for Time-resolved Materials...Yi Lin
Ultrafast electron diffraction (UED) enables direct insight into structural dynamics of solids. Relativistic MeV-scale electron beams yield access to high-momentum scattering and preserve beam coherence, yet their application at high repetition rates for high-sensitivity UED has been limited. We discuss the High Repetition-rate Electron Scattering (HiRES) instrument at Berkeley Lab and its first applications to UED of metallic films and quantum materials. HiRES employs a state-of-the-art photoinjector with RF bunch compression to generate high-brightness, relativistic 0.75 MeV electron pulses with up to 105-106 el./pulse and with highest achievable coherence length of 10 nm. The resulting high momentum range (±10 Å-1) yields access over multiple Brillouin zones. The sub-500 fs electron pulses are provided at 0.1-250 kHz repetition rate, and combined with optical pumping via a 1.03 µm fiber amplifier enable UED of cryogenically cooled materials. We will show examples of first experiments including transient Debye-Waller dynamics in ultrathin metals at kHz repetition rate as well as studies of charge density waves in 2D materials.
Work at LBNL was supported by the DOE Office of Basic Energy Sciences.
Measurement-induced long-distance entanglement of superconducting qubits usin...Ondrej Cernotik
Although superconducting systems provide a promising platform for quantum computing, their networking poses a challenge as they cannot be interfaced to light---the medium used to send quantum signals through channels at room temperature. We show that mechanical oscillators can mediated such coupling and light can be used to measure the joint state of two distant qubits. The measurement provides information on the total spin of the two qubits such that entangled qubit states can be postselected. Entanglement generation is possible without ground-state cooling of the mechanical oscillators for systems with optomechanical cooperativity moderately larger than unity; in addition, our setup tolerates a substantial transmission loss. The approach is scalable to generation of multipartite entanglement and represents a crucial step towards quantum networks with superconducting circuits.
Acoustic Emission (AE) refers to the generation of transient elastic waves produced by a sudden redistribution of stress in a material. When a structure is subjected to an external stimulus (change in pressure, load, or temperature), localized sources trigger the release of energy, in the form of stress waves, which propagate to the surface and are recorded by sensors. With the right equipment and setup, motions on the order of picometers (10 -12 m) can be identified. Sources of AE vary from natural events like earthquakes and rockbursts to the initiation and growth of cracks, slip and dislocation movements, melting, twinning, and phase transformations in metals. In composites, matrix cracking and fiber breakage and debonding contribute to acoustic emissions. AE’s have also been measured and recorded in polymers, wood, and concrete, among other materials.
While words and content are the foundation of interactions and the intent of your website or app, they’re often an afterthought in UX design… However!
· The voice and appearance of content gives your design a personality and an emotional connection
· Friendly assistance — and humor — can put your user at ease
· With simple tweaks and approaches, you can give your design a human touch and voice (no more robots!)
· It's important to test content with users, just as you do your visual design (sorry, lorem ipsum!)
· Most importantly, context and audience trumps all
IMU (inertial measurement unit) has already played significant roles in the control system of aerospace and other vehicle platforms. Due to the maturity and low cost of MEMS technology, IMU starts to penetrate consumer products such as smartphone, wearables and VR/AR devices.
This sharing will focus on the general introduction of IMU components, signal characteristics and application concepts, with an attempt to guide those who is interested in the IMU-based system integration and algorithm development.
CLEO 2009: High Frequency Polarization Switching VCSEL Clock Using Subwavelength Quarter-Wave Plate
by:
Clinton J. Smith, Wen-Di Li, Shufeng Bai, and Stephen Y. Chou
Copper (775) - an optics, 2PPE, and Bulk state simulation studyPo-Chun Yeh
My earlier studies on Cu(775) - a tilt cut highly crystalline copper surface using ultrafast femtosecond laser based 2-photon photoemission and its related simulation via Fortran 77.
This project targets the development of novel pocket X-ray sources and X-ray direct detectors that will be combined in a distributed network to solve important tasks, for example in the field of security, by ensuring reliable and real-time monitoring of failure sensitive parts in large manufacturing plants or in public transportation.
The miniaturized X-ray sources are based on multi-wall carbon nanotube (CNT) cold electron emitters and advanced microsystems technology. The electron field emission properties of CNTs, with their high current densities, make them prime candidates for cold emitter cathodes. Using CNT cold electron emitters will make it possible to miniaturize the whole X-ray source. Additionally, as opposed to classical thermionic emission, field electron emission of the CNT is voltage-controlled which allows for high modulation frequencies up to GHz level. The X-ray direct detectors in turn are based on crystalline germanium absorption layers grown directly on a CMOS sensor chip yielding high resolution and high sensitivity X-ray detectors. Single photon detection will allow for a significant improvement of contrast for applications in security, health care and nondestructive testing.
Kilohertz-Rate MeV Ultrafast Electron Diffraction for Time-resolved Materials...Yi Lin
Ultrafast electron diffraction (UED) enables direct insight into structural dynamics of solids. Relativistic MeV-scale electron beams yield access to high-momentum scattering and preserve beam coherence, yet their application at high repetition rates for high-sensitivity UED has been limited. We discuss the High Repetition-rate Electron Scattering (HiRES) instrument at Berkeley Lab and its first applications to UED of metallic films and quantum materials. HiRES employs a state-of-the-art photoinjector with RF bunch compression to generate high-brightness, relativistic 0.75 MeV electron pulses with up to 105-106 el./pulse and with highest achievable coherence length of 10 nm. The resulting high momentum range (±10 Å-1) yields access over multiple Brillouin zones. The sub-500 fs electron pulses are provided at 0.1-250 kHz repetition rate, and combined with optical pumping via a 1.03 µm fiber amplifier enable UED of cryogenically cooled materials. We will show examples of first experiments including transient Debye-Waller dynamics in ultrathin metals at kHz repetition rate as well as studies of charge density waves in 2D materials.
Work at LBNL was supported by the DOE Office of Basic Energy Sciences.
Measurement-induced long-distance entanglement of superconducting qubits usin...Ondrej Cernotik
Although superconducting systems provide a promising platform for quantum computing, their networking poses a challenge as they cannot be interfaced to light---the medium used to send quantum signals through channels at room temperature. We show that mechanical oscillators can mediated such coupling and light can be used to measure the joint state of two distant qubits. The measurement provides information on the total spin of the two qubits such that entangled qubit states can be postselected. Entanglement generation is possible without ground-state cooling of the mechanical oscillators for systems with optomechanical cooperativity moderately larger than unity; in addition, our setup tolerates a substantial transmission loss. The approach is scalable to generation of multipartite entanglement and represents a crucial step towards quantum networks with superconducting circuits.
Acoustic Emission (AE) refers to the generation of transient elastic waves produced by a sudden redistribution of stress in a material. When a structure is subjected to an external stimulus (change in pressure, load, or temperature), localized sources trigger the release of energy, in the form of stress waves, which propagate to the surface and are recorded by sensors. With the right equipment and setup, motions on the order of picometers (10 -12 m) can be identified. Sources of AE vary from natural events like earthquakes and rockbursts to the initiation and growth of cracks, slip and dislocation movements, melting, twinning, and phase transformations in metals. In composites, matrix cracking and fiber breakage and debonding contribute to acoustic emissions. AE’s have also been measured and recorded in polymers, wood, and concrete, among other materials.
While words and content are the foundation of interactions and the intent of your website or app, they’re often an afterthought in UX design… However!
· The voice and appearance of content gives your design a personality and an emotional connection
· Friendly assistance — and humor — can put your user at ease
· With simple tweaks and approaches, you can give your design a human touch and voice (no more robots!)
· It's important to test content with users, just as you do your visual design (sorry, lorem ipsum!)
· Most importantly, context and audience trumps all
The Role of UA in UX (and Vice Versa): Putting the User in User AssistanceSteve Stegelin
“User assistance indicates a failed design” is a sentiment we sometimes hear from designers, UX professionals, and even other technical communicators. However, “Help” doesn’t have to be a four-letter word. In this talk, we’ll discuss the role UA plays in the overall user experience (spoilers: it plays a big one) and how, likewise, a focus on the user experience of Help can lead to innovative and engaging content. We’ll also take a hard look at our users, how they interact with content, considerations to keep in mind to ensure you engage users and answer their real questions, and whether the traditional tri-pane UX of Help still meets their needs and expectations.
Drupal Commerce is used to build eCommerce websites and applications of all sizes. At its core it is lean and mean, enforcing strict development standards and leveraging the greatest features of Drupal 7 and major modules like Views and Rules for maximum flexibility.
How to build the own ecommerce site ?
Airborne and underground matter-wave interferometers: geodesy, navigation and...Philippe Bouyer
The remarkable success of atom coherent manipulation techniques has motivated competitive research and development in precision metrology. Matter-wave inertial sensors – accelerometers, gyrometers, gravimeters – based on these techniques are all at the forefront of their respective measurement classes. Atom inertial sensors provide nowadays about the best accelerometers and gravimeters and allow, for instance, to make the most precise monitoring of gravity or to device precise tests of the weak equivalence principle (WEP). I present here some recent advances in these fields
Langmuir probe diagnostics at VINETA II experimental apparatusTiziano Fulceri
VINETA II is an experiment to investigate magnetic reconnection in a controlled laboratory environment. The purpose of this work is to test the Langmuir probe diagnostics system by measuring the time evolution of 2D profiles of highly reproducible transient argon plasma discharges generated by an array of 7 electron guns. This is done by positioning the tip of a Langmuir probe at various positions on a 2D plane and by biasing it with an AC voltage with amplitude in the range 60V-80V and frequency in the range 10 kHz – 100 kHz. The end result is a 2D profile evolving in time for each parameter that can be extracted from the probe (T_e, n_e).
The presentation file on workshop on Neutron and X-ray Characterisation on Caloric Materials, introduction to neutron scattering experiment with triple axis spectrometer for material scientist
Presentation in the Franhoufer IIS about my thesis: A wavelet transform based...Pedro Cerón Colás
Presentation in the Franhoufer IIS about my thesis: A wavelet transform based application for seismic waves. Analysis of the performance. Code made in Matlab.
1935 – Heil oscillator
1939 – klystron amplifier
1944 – Helix type TWT
In the early 1950s – low power output of linear beam tubes to high power levels
Finally invention of Magnetrons
Several devices were developed – two significant devices among them are
1) extended interaction klystron
2) Twystron hybrid amplifier
CYLINDRICAL
LINEAR
COAXIAL
VOLTAGE-TUNABLE
INVERTED COAXIAL
FREQUENCY-AGILE COAXIAL
Similar to Joe Kelleher Presentation (May 27th 2014) (20)
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
5. Types
of
experiment:
trends
from
1999
to
2011
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1999
(PEARL)
2002 2005 2008 2011
Strain scanning: welds
Strain scanning: other
In-situ loading, room
temperature
In-situ loading, high
temperature
Other in-situ
processes
Physics of neutron
measurement
In-situ loading, cryo-
temperature
Shareofuserexperimenttime
6. From
materials
to
processes
Magnetic fields
Electrochemical reactions
Mechanical deformation
Heat treatment
Phase transformations
Welding
Fuel cells
Corrosion
Shape memory alloys
Material forming
7. Stressrig
(up
to
100kN)
Cryostat
Down
to
-‐200C
Optical
furnace
Up
to
1100C
Resistance
furnace
(small
samples,
up
to
~1600C)
Sample
environments
for
in-‐
situ
tests
Ceramic
heating
pads
(larger
samples)
8. In-‐situ
heat
treatment
Linear
weld
Ni
superalloy
Circumferential
pipe
weld
Single
crystal
Ni
superalloy
Anna
Paradowska
demonstrates
proof
of
principle
James
Rolph
et
al.
Comptes
Rendus
Physique
13(3):307–
15.
(2012)
Bo
Chen
et
al.
Acta
Materialia
submitted
(2013)
See
γ’
misfit
as
function
of
temperature
9. In-‐situ
heat
treatment
of
pipe
weld
2.865
2.87
2.875
2.88
2.885
2.89
2.895
2.9
0 200 400 600 800
Atomic
la*ce
spacing
/
Å
Temperature
/
°C
Weld... Stress-‐free
reference...
Hea8ng Hea8ng
Cooling Cooling
Bo
Chen,
Alexandros
Skouras,
Yiqiang
Wang,
Joe
Kelleher,
Shu
Yan
Zhang,
David
Smith,
Peter
Flewitt,
Martyn
Pavier
10. Cyclic
voltage
on
PZT
ferroelectric
100
MPa
applied
Zero
load
The
MANTID
platform
§ Data
reduction
and
visualisation
for
all
ISIS
instruments
§ Supports
event
mode
and
stroboscopic
data
David
Hall,
2013
Loading
direction
Transverse
direction
500
V
/
mm
AC
electric
field
Cyclic
electric
field
causes
straining
of
poled
PZT,
but
applied
load
depoles
the
PZT
Plots
show
difference
between
+
and
–
half-‐cycles
–
+
13. Practical
considerations
• Sample
environment
– Sufficiently
non-‐interacting
with
neutron
beam
– ‘Contains’
the
process
for
steady-‐state,
safety
• Timing
for
dynamic
effects
– Synchronise
clocks
or
use
trigger
pulses
– Get
event
mode
acquisition
to
collect
other
data
• Can
we
record
more
than
just
the
neutron
data?
14. Supplementary
analytical
methods
Things
that
might
change
in
a
process
• Mechanical
deformation,
stress
and
strain
• Material
‘damage’
• Phase
changes
• Diffusion
• Temperature
Methods
that
might
reveal
these
changes
• Image
correlation
• Acoustic
emission
• Thermoelastography
• Dilatometry
• Calorimetry
• Ultrasonic
and
magnetic
methods
• Sometimes
possible
to
measure
these
‘for
free’
with
existing
sensors
15. Full-‐spectrum
imaging
• Neutron
detectors
not
intrinsically
sensitive
to
wavelength,
but
to
time
of
detection
– …hence
velocity,
hence
wavelength
• Each
pixel
of
a
2D
detector
can
record
a
full
wavelength
spectrum
• We
can
thus
see
both
spatial
and
temporal
variation
in
several
physical
parameters
16. Time-‐of-‐Klight
neutron
imaging
for
in-‐situ
studies
Bragg
edges
show
crystal
structure
–
how
those
atoms
are
arranged
Resonance
peaks
show
which
atoms/
isotopes
present
Wavelength
Detected
intensity
Height
→
Texture
Height
→
Concentration
Width
→
Temperature
Position
→
Strain
17. Steven
Peetermans
&
Joe
Kelleher
(2013)
17
Transmission
spectrum
from
single
crystal
Σabs+Σinc+Σinel,coh
Σel,coh
Position = Orientation
and strain
Width = Mosaicity
18. Conclusion:
Some
future
directions?
• Broader
array
of
sensing
and
actuation
on
beamlines
–
Users
won’t
need
to
bring
their
own
• Flexible
data
chopping
with
event
mode
– Especially
cyclic
or
highly
dynamic
processes
• Sensor
/
actuator
bus
for
real
time
measurement
and
control
(e.g.
CANBUS
for
vehicles)