This document discusses using high-content screening to identify novel regulators of axon regeneration in the central nervous system. Over 1,000 genes were found to change expression between postnatal days 3 and 16 in rodent corticospinal tract neurons, which lose regenerative ability during this period. A screening workflow involved expressing candidate genes from a library in cultured neurons and automating quantification of neurite outgrowth. Several Kruppel-like factor family members were identified as regulators of neurite outgrowth, with further experiments showing the zinc finger domain activates or represses growth.
The document outlines a research proposal to study the cellular mechanisms underlying cognitive deficits caused by traumatic brain injury (TBI). The central hypothesis is that TBI causes pathological alterations in GABAergic function that lead to imbalances in excitatory and inhibitory synaptic transmission in the hippocampus, resulting in hippocampal dysfunction and cognitive impairment. Three specific aims are described to characterize alterations in GABAergic function in the dentate gyrus and areas CA1 and CA3 of the hippocampus at one week and over months following TBI using electrophysiological and other techniques.
1) The study investigated whether a catalytically inactive tPA variant (tPA-S481A) could prevent impairment of cerebral autoregulation and histopathology after traumatic brain injury (TBI) in piglets.
2) tPA-S481A prevented pial artery vasoconstriction and blunted dilation impairment during hypotension after TBI.
3) tPA-S481A also prevented neuronal cell loss in the hippocampus that normally occurs after TBI.
Derek McGinnis suffered a traumatic brain injury (TBI) from a vehicle-borne improvised explosive device (VBIED) while serving in Iraq in 2004. He spent hours recovering in military and VA facilities. After struggling with memory issues and adapting to life after his injury, he found support from his spouse but also battled post-traumatic stress disorder, anger, and depression. He has since completed an outpatient brain injury recovery program and challenged himself to become a triathlete. Derek still struggles with questions of his identity and lost opportunities from his injury, but has experienced post-traumatic growth through serving others and supporting fellow veterans.
Inflammation persists months to years after spinal cord injury and contributes to neuropathic pain. Analysis of spinal cords from rats 9 months after injury found elevated levels of prostaglandin E2 and leukotriene B4, indicating ongoing inflammation. Treatment with the anti-inflammatory drug licofelone for 28 days enhanced anti-oxidant and anti-inflammatory pathways in the injured spinal cord of rats, reduced pain behavior, and increased exploratory activity, showing targeting chronic inflammation may be a strategy for reducing neuropathic pain following spinal cord injury.
1) LAR is a receptor for chondroitin sulfate proteoglycans (CSPGs), which are inhibitory to axon growth in the central nervous system.
2) CSPGs bind to LAR with high affinity and stimulate its phosphatase activity. Blocking LAR reverses CSPG-mediated growth inhibition.
3) In mouse models of spinal cord injury, peptides targeting LAR promote axon growth, functional recovery, and behavioral improvements by overcoming the inhibitory effects of CSPGs. LAR blockade may be a promising therapeutic approach for central nervous system axon injury.
This document provides information about research funding opportunities within the VA Office of Research and Development (ORD) for traumatic brain injury (TBI). It outlines the ORD leadership and research services divisions. All applicants for VA research funds must hold a minimum 5/8th VA salaried position. Funding mechanisms include Career Development Awards for early, mid, and senior-level researchers; Merit Awards for 1-4 year projects up to $275K per year; Pilot Awards for 1-2 year projects up to $100K per year; and Center of Excellence awards for 5 year projects up to $1M per year.
1. The document discusses the clinical use of a portable head CT scanner called CereTom that can scan patients at their bedside. Between 2006-2009, 3421 portable CT scans were performed, with 95.8% in the neuroscience ICU.
2. Scans were used to guide treatment for conditions like traumatic brain injury, hemorrhage, and stroke. Quantitative CBF data from scans helped guide decisions around blood pressure management and other physiological variables.
3. Portable CT allowed scanning of critically ill patients without the risks of moving them, and provided rapid anatomical and physiological data to guide critical care decisions at the patient's bedside.
This study used magnetic resonance spectroscopy to examine metabolic concentrations in the anterior cingulate cortex of individuals with spinal cord injuries and neuropathic pain. It found that higher pain severity and greater psychosocial impact were associated with metabolic markers suggesting neuronal dysfunction and glial activation. A cluster analysis identified two subgroups - one with high pain impact and low neuronal/glial ratios, and another with low impact and higher ratios. Compared to controls, those with SCI and high pain impact had less favorable neuronal/glial ratios and greater psychosocial effects. The results support the hypothesis that greater pain is linked to anterior cingulate cortex changes reflecting decreased pain modulation.
The document outlines a research proposal to study the cellular mechanisms underlying cognitive deficits caused by traumatic brain injury (TBI). The central hypothesis is that TBI causes pathological alterations in GABAergic function that lead to imbalances in excitatory and inhibitory synaptic transmission in the hippocampus, resulting in hippocampal dysfunction and cognitive impairment. Three specific aims are described to characterize alterations in GABAergic function in the dentate gyrus and areas CA1 and CA3 of the hippocampus at one week and over months following TBI using electrophysiological and other techniques.
1) The study investigated whether a catalytically inactive tPA variant (tPA-S481A) could prevent impairment of cerebral autoregulation and histopathology after traumatic brain injury (TBI) in piglets.
2) tPA-S481A prevented pial artery vasoconstriction and blunted dilation impairment during hypotension after TBI.
3) tPA-S481A also prevented neuronal cell loss in the hippocampus that normally occurs after TBI.
Derek McGinnis suffered a traumatic brain injury (TBI) from a vehicle-borne improvised explosive device (VBIED) while serving in Iraq in 2004. He spent hours recovering in military and VA facilities. After struggling with memory issues and adapting to life after his injury, he found support from his spouse but also battled post-traumatic stress disorder, anger, and depression. He has since completed an outpatient brain injury recovery program and challenged himself to become a triathlete. Derek still struggles with questions of his identity and lost opportunities from his injury, but has experienced post-traumatic growth through serving others and supporting fellow veterans.
Inflammation persists months to years after spinal cord injury and contributes to neuropathic pain. Analysis of spinal cords from rats 9 months after injury found elevated levels of prostaglandin E2 and leukotriene B4, indicating ongoing inflammation. Treatment with the anti-inflammatory drug licofelone for 28 days enhanced anti-oxidant and anti-inflammatory pathways in the injured spinal cord of rats, reduced pain behavior, and increased exploratory activity, showing targeting chronic inflammation may be a strategy for reducing neuropathic pain following spinal cord injury.
1) LAR is a receptor for chondroitin sulfate proteoglycans (CSPGs), which are inhibitory to axon growth in the central nervous system.
2) CSPGs bind to LAR with high affinity and stimulate its phosphatase activity. Blocking LAR reverses CSPG-mediated growth inhibition.
3) In mouse models of spinal cord injury, peptides targeting LAR promote axon growth, functional recovery, and behavioral improvements by overcoming the inhibitory effects of CSPGs. LAR blockade may be a promising therapeutic approach for central nervous system axon injury.
This document provides information about research funding opportunities within the VA Office of Research and Development (ORD) for traumatic brain injury (TBI). It outlines the ORD leadership and research services divisions. All applicants for VA research funds must hold a minimum 5/8th VA salaried position. Funding mechanisms include Career Development Awards for early, mid, and senior-level researchers; Merit Awards for 1-4 year projects up to $275K per year; Pilot Awards for 1-2 year projects up to $100K per year; and Center of Excellence awards for 5 year projects up to $1M per year.
1. The document discusses the clinical use of a portable head CT scanner called CereTom that can scan patients at their bedside. Between 2006-2009, 3421 portable CT scans were performed, with 95.8% in the neuroscience ICU.
2. Scans were used to guide treatment for conditions like traumatic brain injury, hemorrhage, and stroke. Quantitative CBF data from scans helped guide decisions around blood pressure management and other physiological variables.
3. Portable CT allowed scanning of critically ill patients without the risks of moving them, and provided rapid anatomical and physiological data to guide critical care decisions at the patient's bedside.
This study used magnetic resonance spectroscopy to examine metabolic concentrations in the anterior cingulate cortex of individuals with spinal cord injuries and neuropathic pain. It found that higher pain severity and greater psychosocial impact were associated with metabolic markers suggesting neuronal dysfunction and glial activation. A cluster analysis identified two subgroups - one with high pain impact and low neuronal/glial ratios, and another with low impact and higher ratios. Compared to controls, those with SCI and high pain impact had less favorable neuronal/glial ratios and greater psychosocial effects. The results support the hypothesis that greater pain is linked to anterior cingulate cortex changes reflecting decreased pain modulation.
This document provides an overview of acute renal failure (ARF), including definitions, epidemiology, diagnostic workup, specific syndromes, treatment, and prevention strategies. It discusses the etiology of ARF, including pre-renal, intra-renal, and post-renal causes. Pre-renal ARF can be caused by factors like volume depletion, NSAIDs, and ACE inhibitors. Intra-renal ARF includes vascular occlusion, glomerular diseases, tubular disorders like crystal nephropathy, and interstitial nephritis. Effective prevention strategies for ischemic acute tubular necrosis (ATN) include maintaining euvolemia through fluid hydration.
Acute renal failure is a common condition in hospitalized patients with a high mortality rate. While many patients recover from ARF, a significant number do not survive. The document discusses the definitions, epidemiology, etiologies, diagnostic workup, treatment and prevention of ARF. It emphasizes that the most effective preventive strategy is to maintain proper fluid volume status in at-risk patients. Biomarkers are being investigated to aid early diagnosis but hydration remains the key prevention method.
The document summarizes research on knockout rat models lacking key drug transporter genes. It describes the development of knockout rats for the drug transporters Mdr1a, Bcrp, Mrp1, Mrp2, and p53 using zinc finger nuclease technology. This allows for improved prediction of drug absorption, distribution, metabolism, and excretion (ADME) properties. Data is presented comparing substrate drug levels and expression of other transporters in knockout versus wild type rats for several of these models. The goal is to enable more efficient drug development by identifying safety issues earlier in the process using a more human-relevant species.
Preliminary report describing a targeted sequencing study in 1500 MS cases and 1500 controls. I presented this at the ASHG 2011 session on large scale resequencing.
The document discusses different classifications of hereditary ataxias including congenital cerebellar ataxias, metabolic ataxias, ataxias associated with defective DNA repair, and degenerative ataxias. It focuses on pathogenic classifications including mitochondrial, metabolic, associated with defective DNA repair, protein folding and degradation, channelopathies, toxic RNA, and others. Specific mitochondrial ataxias caused by nuclear and mitochondrial genes are examined in depth, including Friedreich's ataxia. Disorders associated with defective DNA repair including ataxia telangiectasia, ataxia oculomotor apraxia types 1 and 2 are also summarized.
The document discusses how AP-2α induces apoptosis in cancer cells. It finds that AP-2α activates the intrinsic apoptosis pathway by binding to the Bcl-2 promoter and repressing its transcription. This allows Bax to translocate to mitochondria, disrupt membrane potential, and release cytochrome c, activating caspase-9 and caspase-3. Downregulation of anti-apoptotic Bcl-2 is important for AP-2α-induced apoptosis. Overexpressing AP-2α enhances cancer cell chemosensitivity to various drugs.
Evgeny nikolaev proteomics of body liquids as a source for potential methods ...igorod
The document discusses using mass spectrometry to analyze body fluids like urine, saliva, and exhaled breath condensate for medical diagnostics and biomarker discovery. It describes creating databases of accurate mass tags and retention times from mass spec analyses of peptides and proteins in body fluids to enable fast identification. Biomarkers found for diseases like COPD, pneumonia and changes after lung transplantation are mentioned.
This document discusses ChIP-Atlas, a database of chromatin immunoprecipitation sequencing (ChIP-seq) data. It contains over 1,000 TB of ChIP-seq data from thousands of experiments profiling transcription factor and histone modifications across various cell types. The database can be used to identify transcription factors enriched at tissue-specific genes and provides tools to analyze ChIP-seq data, including a peak browser and enrichment analysis. It aims to facilitate understanding of gene regulation networks in different cell types.
In order to provide an adequate response that allows the elimination of insults while preserving self, the immune system is tightly regulated by a balance between activating and inhibitory signals. Multiple mechanisms exist to accomplish this task, including the expression of activating and inhibitory receptors by immune cells. The CD300 family of receptors are type I transmembrane proteins that forms an arrayed receptor system that is able to recognize the viability and activation status of cells, and consequently have a significant influence on the final outcome of the immune response. The very recent discovery that CD300 molecules are able to recognize lipids, such as phosphatidylserine, and phosphatidylethanolamine that are exposed on the outer leaflet of the plasma membrane of dead and activated cells has opened a new field of research. Through their binding to lipids and other ligands, this family of receptors is poised to have a significant role in complex biological processes and in the host response to severe pathological conditions. Expression of CD300 molecules is altered in a number of diseases and anti-CD300 antibodies have been demonstrated to have significant therapeutic effect in several animal models. The mechanisms underlying the immunoregulatory effects of the CD300 family are complex and deciphering their signaling properties will allow effective targeting of these molecules as novel therapies in a wide variety of inflammatory and immune-mediated diseases.
The DTExtm method allows simultaneous analysis of changes in gene expression levels of 145 ADME-associated genes using a microarray. Total RNA is converted to cDNA and labeled before being hybridized to the DTExtm microarray. The method can survey basal gene expression levels and coordinated changes in expression levels caused by drug treatment in various cell lines and tissues. Rifampicin treatment of human hepatocytes showed induction of genes such as CYP3A4, UGT1A1, and ABCB1 in a coordinated manner mediated by PXR activation. Benzoflavone treatment also coordinately induced CYP1A2, UGT1A1, and ABCC2 through AHR activation. DTE
OPG expression in intestinal epithelial cells appears to be suppressed when exposed to commensal bacteria. OPG binds to both live and killed bacteria and this bound OPG can be released through detergent treatment. Treatment of Caco 2 cell supernatants with detergent does not increase detectable OPG levels by ELISA, indicating ELISA detects the true OPG concentration.
This document summarizes key aspects of mantle cell lymphoma (MCL) biology and pathogenesis. It discusses:
1) MCL is characterized by the t(11;14) translocation resulting in cyclin D1 overexpression. Prognosis is poor with median survival of 3-4 years, though survival has improved with new therapies.
2) MCL pathogenesis involves dysregulation of cell cycle control and DNA damage response pathways. Genetic alterations affect genes like ATM, p53, ARF-INK4a locus, MDM2, CDK4/cyclin D, and RB.
3) MCL demonstrates a spectrum of variants from classical to blastoid based on proliferation. Bi
This document summarizes key aspects of mantle cell lymphoma (MCL) biology and pathogenesis. It discusses:
1) MCL is characterized by the t(11;14) translocation resulting in cyclin D1 overexpression. Prognosis is poor with median survival of 3-4 years, though survival has improved with new therapies.
2) MCL pathogenesis involves dysregulation of cell cycle control and DNA damage response pathways. Genetic alterations affect genes like ATM, p53, ARF-INK4a locus, MDM2, CDK4/cyclin D, and RB.
3) MCL demonstrates a spectrum of variants from classical to blastoid based on proliferation. Bi
1) Oxidative stress and mitochondrial dysfunction play a key role in neuronal apoptosis following acute brain injuries like spinal cord injury and traumatic brain injury. 2) The STAT3 transcription factor regulates the expression of the mitochondrial antioxidant enzyme MnSOD (SOD2) which reduces oxidative stress. 3) Activating the IL-6/STAT3/MnSOD pathway may be neuroprotective by reducing mitochondrial oxidative stress and neuronal death following brain injuries.
1) Assessment of effort is important in TBI clinical practice and research to generate valid data on patients' true cognitive capacities, as poor effort is common and can invalidate test results.
2) Formal effort tests should be integrated into evaluations to detect exaggeration and rule out other factors, given the effects of poor effort can dwarf those of mild TBI.
3) Various external incentives like compensation can adversely impact effort, so it is important to consider effort and response bias in clinical and research work involving people with TBI.
Ross Zafonte is a professor and chairman at Harvard Medical School. He holds the position of chairman, which is a leadership role within an academic department. As chairman, he oversees the department and provides guidance to faculty and students.
This document provides an overview of acute renal failure (ARF), including definitions, epidemiology, diagnostic workup, specific syndromes, treatment, and prevention strategies. It discusses the etiology of ARF, including pre-renal, intra-renal, and post-renal causes. Pre-renal ARF can be caused by factors like volume depletion, NSAIDs, and ACE inhibitors. Intra-renal ARF includes vascular occlusion, glomerular diseases, tubular disorders like crystal nephropathy, and interstitial nephritis. Effective prevention strategies for ischemic acute tubular necrosis (ATN) include maintaining euvolemia through fluid hydration.
Acute renal failure is a common condition in hospitalized patients with a high mortality rate. While many patients recover from ARF, a significant number do not survive. The document discusses the definitions, epidemiology, etiologies, diagnostic workup, treatment and prevention of ARF. It emphasizes that the most effective preventive strategy is to maintain proper fluid volume status in at-risk patients. Biomarkers are being investigated to aid early diagnosis but hydration remains the key prevention method.
The document summarizes research on knockout rat models lacking key drug transporter genes. It describes the development of knockout rats for the drug transporters Mdr1a, Bcrp, Mrp1, Mrp2, and p53 using zinc finger nuclease technology. This allows for improved prediction of drug absorption, distribution, metabolism, and excretion (ADME) properties. Data is presented comparing substrate drug levels and expression of other transporters in knockout versus wild type rats for several of these models. The goal is to enable more efficient drug development by identifying safety issues earlier in the process using a more human-relevant species.
Preliminary report describing a targeted sequencing study in 1500 MS cases and 1500 controls. I presented this at the ASHG 2011 session on large scale resequencing.
The document discusses different classifications of hereditary ataxias including congenital cerebellar ataxias, metabolic ataxias, ataxias associated with defective DNA repair, and degenerative ataxias. It focuses on pathogenic classifications including mitochondrial, metabolic, associated with defective DNA repair, protein folding and degradation, channelopathies, toxic RNA, and others. Specific mitochondrial ataxias caused by nuclear and mitochondrial genes are examined in depth, including Friedreich's ataxia. Disorders associated with defective DNA repair including ataxia telangiectasia, ataxia oculomotor apraxia types 1 and 2 are also summarized.
The document discusses how AP-2α induces apoptosis in cancer cells. It finds that AP-2α activates the intrinsic apoptosis pathway by binding to the Bcl-2 promoter and repressing its transcription. This allows Bax to translocate to mitochondria, disrupt membrane potential, and release cytochrome c, activating caspase-9 and caspase-3. Downregulation of anti-apoptotic Bcl-2 is important for AP-2α-induced apoptosis. Overexpressing AP-2α enhances cancer cell chemosensitivity to various drugs.
Evgeny nikolaev proteomics of body liquids as a source for potential methods ...igorod
The document discusses using mass spectrometry to analyze body fluids like urine, saliva, and exhaled breath condensate for medical diagnostics and biomarker discovery. It describes creating databases of accurate mass tags and retention times from mass spec analyses of peptides and proteins in body fluids to enable fast identification. Biomarkers found for diseases like COPD, pneumonia and changes after lung transplantation are mentioned.
This document discusses ChIP-Atlas, a database of chromatin immunoprecipitation sequencing (ChIP-seq) data. It contains over 1,000 TB of ChIP-seq data from thousands of experiments profiling transcription factor and histone modifications across various cell types. The database can be used to identify transcription factors enriched at tissue-specific genes and provides tools to analyze ChIP-seq data, including a peak browser and enrichment analysis. It aims to facilitate understanding of gene regulation networks in different cell types.
In order to provide an adequate response that allows the elimination of insults while preserving self, the immune system is tightly regulated by a balance between activating and inhibitory signals. Multiple mechanisms exist to accomplish this task, including the expression of activating and inhibitory receptors by immune cells. The CD300 family of receptors are type I transmembrane proteins that forms an arrayed receptor system that is able to recognize the viability and activation status of cells, and consequently have a significant influence on the final outcome of the immune response. The very recent discovery that CD300 molecules are able to recognize lipids, such as phosphatidylserine, and phosphatidylethanolamine that are exposed on the outer leaflet of the plasma membrane of dead and activated cells has opened a new field of research. Through their binding to lipids and other ligands, this family of receptors is poised to have a significant role in complex biological processes and in the host response to severe pathological conditions. Expression of CD300 molecules is altered in a number of diseases and anti-CD300 antibodies have been demonstrated to have significant therapeutic effect in several animal models. The mechanisms underlying the immunoregulatory effects of the CD300 family are complex and deciphering their signaling properties will allow effective targeting of these molecules as novel therapies in a wide variety of inflammatory and immune-mediated diseases.
The DTExtm method allows simultaneous analysis of changes in gene expression levels of 145 ADME-associated genes using a microarray. Total RNA is converted to cDNA and labeled before being hybridized to the DTExtm microarray. The method can survey basal gene expression levels and coordinated changes in expression levels caused by drug treatment in various cell lines and tissues. Rifampicin treatment of human hepatocytes showed induction of genes such as CYP3A4, UGT1A1, and ABCB1 in a coordinated manner mediated by PXR activation. Benzoflavone treatment also coordinately induced CYP1A2, UGT1A1, and ABCC2 through AHR activation. DTE
OPG expression in intestinal epithelial cells appears to be suppressed when exposed to commensal bacteria. OPG binds to both live and killed bacteria and this bound OPG can be released through detergent treatment. Treatment of Caco 2 cell supernatants with detergent does not increase detectable OPG levels by ELISA, indicating ELISA detects the true OPG concentration.
This document summarizes key aspects of mantle cell lymphoma (MCL) biology and pathogenesis. It discusses:
1) MCL is characterized by the t(11;14) translocation resulting in cyclin D1 overexpression. Prognosis is poor with median survival of 3-4 years, though survival has improved with new therapies.
2) MCL pathogenesis involves dysregulation of cell cycle control and DNA damage response pathways. Genetic alterations affect genes like ATM, p53, ARF-INK4a locus, MDM2, CDK4/cyclin D, and RB.
3) MCL demonstrates a spectrum of variants from classical to blastoid based on proliferation. Bi
This document summarizes key aspects of mantle cell lymphoma (MCL) biology and pathogenesis. It discusses:
1) MCL is characterized by the t(11;14) translocation resulting in cyclin D1 overexpression. Prognosis is poor with median survival of 3-4 years, though survival has improved with new therapies.
2) MCL pathogenesis involves dysregulation of cell cycle control and DNA damage response pathways. Genetic alterations affect genes like ATM, p53, ARF-INK4a locus, MDM2, CDK4/cyclin D, and RB.
3) MCL demonstrates a spectrum of variants from classical to blastoid based on proliferation. Bi
1) Oxidative stress and mitochondrial dysfunction play a key role in neuronal apoptosis following acute brain injuries like spinal cord injury and traumatic brain injury. 2) The STAT3 transcription factor regulates the expression of the mitochondrial antioxidant enzyme MnSOD (SOD2) which reduces oxidative stress. 3) Activating the IL-6/STAT3/MnSOD pathway may be neuroprotective by reducing mitochondrial oxidative stress and neuronal death following brain injuries.
1) Assessment of effort is important in TBI clinical practice and research to generate valid data on patients' true cognitive capacities, as poor effort is common and can invalidate test results.
2) Formal effort tests should be integrated into evaluations to detect exaggeration and rule out other factors, given the effects of poor effort can dwarf those of mild TBI.
3) Various external incentives like compensation can adversely impact effort, so it is important to consider effort and response bias in clinical and research work involving people with TBI.
Ross Zafonte is a professor and chairman at Harvard Medical School. He holds the position of chairman, which is a leadership role within an academic department. As chairman, he oversees the department and provides guidance to faculty and students.
The document discusses strategies for translating scientific research on traumatic brain injury (TBI) and clinical practices to end users through social media. It outlines results from surveys of people with TBI or caring for someone with TBI that found they are interested in topics like memory, depression, and relationships and prefer video and text formats. The document recommends partnering with popular websites and social media to distribute information on TBI to a wider audience in multiple formats and lay language.
The document discusses using microdialysis catheters to monitor brain chemistry in patients with brain injuries. Monitoring markers like glucose, lactate, pyruvate, and glycerol levels can provide information about brain energy metabolism and cell damage. Optimizing factors like blood flow, oxygen and glucose delivery through drugs or surgery may improve tissue repair and survival. Different brain regions may require different intensive care treatments based on their chemistry profiles to reverse pathology and improve outcomes. Case studies are presented showing how monitoring chemistry over time can demonstrate the effects of interventions.
The document discusses brain tissue oxygenation (PbtO2) monitoring in neurointensive care units. PbtO2 directly measures oxygen levels in brain tissue and is used to detect cerebral ischemia. Low PbtO2 values are associated with increased mortality risk and various treatments can be used to improve PbtO2 levels and outcomes for patients with severe traumatic brain injury. The document reviews guidelines, indications, techniques, and complications of PbtO2 monitoring.
This document summarizes research on diverse mechanisms of blast-induced neurotrauma in rat models. It finds that exposure to a single "composite" blast, which includes head acceleration, results in cerebrovascular damage, astrocyte activation (glyosis), and neuronal injury. A single "primary" blast exposure instigated predominantly systemic/vascular changes and glyosis. The positional orientation of the animal relative to the shock wave influences whether a composite or primary blast is experienced. Responses depend on the type and magnitude of blast exposure.
This document summarizes a presentation on mitochondrial dysfunction following traumatic brain injury (TBI) and spinal cord injury (SCI). It discusses how mitochondrial dysfunction manifests over time after injury and contributes to cell death through calcium overload and oxidative damage. The presentation shows that mitochondrial function is acutely lost after injury in a severity-dependent manner. Mitochondrial calcium buffering capacity, bioenergetics, and markers of oxidative damage are disrupted for up to 24 hours following injury. Early treatment with antioxidants may help preserve mitochondrial integrity and reduce oxidative damage in the first hours after injury.
This document discusses diffuse axonal injury (DAI), a type of traumatic brain injury seen in fatal TBI cases. It provides a historical perspective on DAI and reviews the pathology, including microscopic findings. DAI involves damage to axons throughout the brain and is graded based on its severity and location. While commonly seen in fatal TBI, the pathology of mild DAI requires further study. The document also describes a unique brain tissue archive containing over 2,000 traumatic brain injury cases accrued over decades that has been used in over 150 publications to better understand DAI and its association with neurodegenerative conditions.
The document summarizes a presentation given by Evan Y. Snyder on strategies for enhancing neural stem cell efficacy in the central nervous system. Some key points:
1) Neural stem cells can rescue injured cells through direct cell-cell contact via gap junctions, as well as secreting diffusible factors. This contact may improve homing of stem cells to injured sites and influence host cell differentiation.
2) In disease models, neural stem cells appear to rescue endangered cells by modulating intracellular signaling pathways related to trophic factors and mitochondrial function. Cell-cell contact through gap junctions plays a role in this rescue.
3) Neural stem cells provide therapeutic benefits not just through cell replacement but also through parac
1) Demyelination is a major feature of many central nervous system disorders and injuries like traumatic brain injury, but it has not been extensively examined in TBI.
2) Studies show oligodendrocyte death and loss of myelin occurring acutely and for weeks/months after TBI in humans and animal models.
3) It is unknown whether demyelination and dysfunctional myelin play a role in long-term axonal degeneration observed after TBI, or if myelin and oligodendrocyte damage are merely epiphenomena with no causal link to neurodegeneration. More research is needed to investigate these questions.
1) The document discusses whether diffuse axonal injury (DAI), the primary pathology seen in non-blast traumatic brain injury, is also present following mild blast brain injury.
2) Animal studies using shock tubes have found only limited axonal swelling and darker staining of brain regions following blast, without extensive DAI.
3) The pathologies observed do not fully match current hypotheses about mild blast brain injury in humans, which have not found hemorrhage or extensive DAI seen in non-blast injury.
4) It remains unclear whether swollen axons are the predominant pathology in DAI or if blast causes an as yet undetected type of subcellular damage.
Justin Sanchez is an Associate Professor at the University of Miami. He holds a PhD and teaches at the University of Miami. The document provides basic biographical information about Justin Sanchez and his role as an Associate Professor at the University of Miami.
This document discusses oligodendrocytes, the cells that form myelin in the central nervous system. It describes their role in development, diseases like multiple sclerosis where remyelination fails, and potential therapies to promote remyelination. A clinical trial was conducted using neural progenitor cell transplantation to treat Pelizaeus-Merzbacher disease, a fatal leukodystrophy caused by myelin deficiency. Research suggests the Wnt signaling pathway inhibits oligodendrocyte differentiation and myelination, and a small molecule Wnt inhibitor was found to accelerate remyelination in mice.
Ali Rezai is the director of the OSU Center for Neuromodulation at Ohio State University. He holds an MD and leads the center, which focuses on neuromodulation research and treatment. The document provides brief biographical information about Ali Rezai and his role as director of the OSU Center for Neuromodulation.
This document discusses the use of transcranial Doppler (TCD) ultrasound for monitoring patients with wartime traumatic brain injury (TBI). TCD is useful for detecting cerebral vasospasm and elevated intracranial pressure, which are common secondary injuries after severe TBI. The study found that over 60% of patients with wartime TBI showed signs of vasospasm on TCD monitoring. TCD was effective at detecting vasospasm both before and after treatments like transluminal balloon angioplasty. Close TCD monitoring is recommended for managing post-traumatic vasospasm in severe TBI patients.
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.
Hunter Peckham is a professor of engineering at Case Western Reserve University. He holds a PhD from Case Western Reserve University and works at their Donnell Institute. Peckham has the title of Professor of Engineering at Case Western Reserve University's Donnell Institute.
1. The document discusses how small changes in redox state, or oxidative status, can have big effects on precursor cell function, survival, death, and differentiation.
2. Certain environmental toxicants are pro-oxidants that can alter redox state and impair precursor cell development, increasing vulnerability to stressors.
3. The redox/Fyn/c-Cbl signaling pathway regulates precursor cell behavior in response to changes in redox state from signaling molecules and toxicants. Modulation of this pathway could optimize tissue repair.
This document discusses diffusion tensor imaging (DTI) and its ability to detect microstructural changes in white matter following mild traumatic brain injury (mTBI). It summarizes several studies conducted by the author and colleagues using 3T MRI-DTI showing that DTI measures of white matter anisotropy correlate with cognitive processing speed and are sensitive to damage in specific tracts related to attention and memory. The document also discusses newer analytical techniques for DTI, such as independent component analysis and connectomics, and their potential for gaining insights into global brain connectivity changes and importance maps for network disruption caused by mTBI.
1) Multiple mild concussive brain injuries in mice can cause cumulative cognitive deficits, as measured by the Morris water maze test, even without structural brain damage.
2) Increasing the time between injuries can reduce these cognitive effects, with monthly intervals showing less impairment than daily injuries.
3) However, while longer intervals between injuries may diminish short-term cognitive effects, it may not fully prevent long-term effects seen one year later.
This presentation provides valuable insights into effective cost-saving techniques on AWS. Learn how to optimize your AWS resources by rightsizing, increasing elasticity, picking the right storage class, and choosing the best pricing model. Additionally, discover essential governance mechanisms to ensure continuous cost efficiency. Whether you are new to AWS or an experienced user, this presentation provides clear and practical tips to help you reduce your cloud costs and get the most out of your budget.
HCL Notes and Domino License Cost Reduction in the World of DLAUpanagenda
Webinar Recording: https://www.panagenda.com/webinars/hcl-notes-and-domino-license-cost-reduction-in-the-world-of-dlau/
The introduction of DLAU and the CCB & CCX licensing model caused quite a stir in the HCL community. As a Notes and Domino customer, you may have faced challenges with unexpected user counts and license costs. You probably have questions on how this new licensing approach works and how to benefit from it. Most importantly, you likely have budget constraints and want to save money where possible. Don’t worry, we can help with all of this!
We’ll show you how to fix common misconfigurations that cause higher-than-expected user counts, and how to identify accounts which you can deactivate to save money. There are also frequent patterns that can cause unnecessary cost, like using a person document instead of a mail-in for shared mailboxes. We’ll provide examples and solutions for those as well. And naturally we’ll explain the new licensing model.
Join HCL Ambassador Marc Thomas in this webinar with a special guest appearance from Franz Walder. It will give you the tools and know-how to stay on top of what is going on with Domino licensing. You will be able lower your cost through an optimized configuration and keep it low going forward.
These topics will be covered
- Reducing license cost by finding and fixing misconfigurations and superfluous accounts
- How do CCB and CCX licenses really work?
- Understanding the DLAU tool and how to best utilize it
- Tips for common problem areas, like team mailboxes, functional/test users, etc
- Practical examples and best practices to implement right away
Dive into the realm of operating systems (OS) with Pravash Chandra Das, a seasoned Digital Forensic Analyst, as your guide. 🚀 This comprehensive presentation illuminates the core concepts, types, and evolution of OS, essential for understanding modern computing landscapes.
Beginning with the foundational definition, Das clarifies the pivotal role of OS as system software orchestrating hardware resources, software applications, and user interactions. Through succinct descriptions, he delineates the diverse types of OS, from single-user, single-task environments like early MS-DOS iterations, to multi-user, multi-tasking systems exemplified by modern Linux distributions.
Crucial components like the kernel and shell are dissected, highlighting their indispensable functions in resource management and user interface interaction. Das elucidates how the kernel acts as the central nervous system, orchestrating process scheduling, memory allocation, and device management. Meanwhile, the shell serves as the gateway for user commands, bridging the gap between human input and machine execution. 💻
The narrative then shifts to a captivating exploration of prominent desktop OSs, Windows, macOS, and Linux. Windows, with its globally ubiquitous presence and user-friendly interface, emerges as a cornerstone in personal computing history. macOS, lauded for its sleek design and seamless integration with Apple's ecosystem, stands as a beacon of stability and creativity. Linux, an open-source marvel, offers unparalleled flexibility and security, revolutionizing the computing landscape. 🖥️
Moving to the realm of mobile devices, Das unravels the dominance of Android and iOS. Android's open-source ethos fosters a vibrant ecosystem of customization and innovation, while iOS boasts a seamless user experience and robust security infrastructure. Meanwhile, discontinued platforms like Symbian and Palm OS evoke nostalgia for their pioneering roles in the smartphone revolution.
The journey concludes with a reflection on the ever-evolving landscape of OS, underscored by the emergence of real-time operating systems (RTOS) and the persistent quest for innovation and efficiency. As technology continues to shape our world, understanding the foundations and evolution of operating systems remains paramount. Join Pravash Chandra Das on this illuminating journey through the heart of computing. 🌟
Ivanti’s Patch Tuesday breakdown goes beyond patching your applications and brings you the intelligence and guidance needed to prioritize where to focus your attention first. Catch early analysis on our Ivanti blog, then join industry expert Chris Goettl for the Patch Tuesday Webinar Event. There we’ll do a deep dive into each of the bulletins and give guidance on the risks associated with the newly-identified vulnerabilities.
Ocean lotus Threat actors project by John Sitima 2024 (1).pptxSitimaJohn
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Fueling AI with Great Data with Airbyte WebinarZilliz
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Generating privacy-protected synthetic data using Secludy and MilvusZilliz
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Let's Integrate MuleSoft RPA, COMPOSER, APM with AWS IDP along with Slackshyamraj55
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Skybuffer AI: Advanced Conversational and Generative AI Solution on SAP Busin...Tatiana Kojar
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With Skybuffer AI, various AI models can be integrated into a single communication channel such as Microsoft Teams. This integration empowers business users with insights drawn from SAP backend systems, enterprise documents, and the expansive knowledge of Generative AI. And the best part of it is that it is all managed through our intuitive no-code Action Server interface, requiring no extensive coding knowledge and making the advanced AI accessible to more users.
5th LF Energy Power Grid Model Meet-up SlidesDanBrown980551
5th Power Grid Model Meet-up
It is with great pleasure that we extend to you an invitation to the 5th Power Grid Model Meet-up, scheduled for 6th June 2024. This event will adopt a hybrid format, allowing participants to join us either through an online Mircosoft Teams session or in person at TU/e located at Den Dolech 2, Eindhoven, Netherlands. The meet-up will be hosted by Eindhoven University of Technology (TU/e), a research university specializing in engineering science & technology.
Power Grid Model
The global energy transition is placing new and unprecedented demands on Distribution System Operators (DSOs). Alongside upgrades to grid capacity, processes such as digitization, capacity optimization, and congestion management are becoming vital for delivering reliable services.
Power Grid Model is an open source project from Linux Foundation Energy and provides a calculation engine that is increasingly essential for DSOs. It offers a standards-based foundation enabling real-time power systems analysis, simulations of electrical power grids, and sophisticated what-if analysis. In addition, it enables in-depth studies and analysis of the electrical power grid’s behavior and performance. This comprehensive model incorporates essential factors such as power generation capacity, electrical losses, voltage levels, power flows, and system stability.
Power Grid Model is currently being applied in a wide variety of use cases, including grid planning, expansion, reliability, and congestion studies. It can also help in analyzing the impact of renewable energy integration, assessing the effects of disturbances or faults, and developing strategies for grid control and optimization.
What to expect
For the upcoming meetup we are organizing, we have an exciting lineup of activities planned:
-Insightful presentations covering two practical applications of the Power Grid Model.
-An update on the latest advancements in Power Grid -Model technology during the first and second quarters of 2024.
-An interactive brainstorming session to discuss and propose new feature requests.
-An opportunity to connect with fellow Power Grid Model enthusiasts and users.
Salesforce Integration for Bonterra Impact Management (fka Social Solutions A...Jeffrey Haguewood
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We believe integration and automation are essential to user experience and the promise of efficient work through technology. Automation is the critical ingredient to realizing that full vision. We develop integration products and services for Bonterra Case Management software to support the deployment of automations for a variety of use cases.
This video focuses on integration of Salesforce with Bonterra Impact Management.
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Introduction of Cybersecurity with OSS at Code Europe 2024Hiroshi SHIBATA
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The first topic is CVE (Common Vulnerabilities and Exposures). I have published CVEs many times. But what exactly is a CVE? I'll provide a basic understanding of CVEs and explain how to detect and handle vulnerabilities in OSS.
Next, let's discuss package managers. Package managers play a critical role in the OSS ecosystem. I'll explain how to manage library dependencies in your application.
I'll share insights into how the Ruby and RubyGems core team works to keep our ecosystem safe. By the end of this talk, you'll have a better understanding of how to safeguard your code.
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Interested in deploying letter generation automations for Bonterra Impact Management? Contact us at sales@sidekicksolutionsllc.com to discuss next steps.
TrustArc Webinar - 2024 Global Privacy SurveyTrustArc
How does your privacy program stack up against your peers? What challenges are privacy teams tackling and prioritizing in 2024?
In the fifth annual Global Privacy Benchmarks Survey, we asked over 1,800 global privacy professionals and business executives to share their perspectives on the current state of privacy inside and outside of their organizations. This year’s report focused on emerging areas of importance for privacy and compliance professionals, including considerations and implications of Artificial Intelligence (AI) technologies, building brand trust, and different approaches for achieving higher privacy competence scores.
See how organizational priorities and strategic approaches to data security and privacy are evolving around the globe.
This webinar will review:
- The top 10 privacy insights from the fifth annual Global Privacy Benchmarks Survey
- The top challenges for privacy leaders, practitioners, and organizations in 2024
- Key themes to consider in developing and maintaining your privacy program
Azure API Management to expose backend services securely
Blackmore, Murray
1. HIGH CONTENT SCREENING
IDENTIFIES NOVEL REGULATORS
OF CNS AXON REGENERATION
Murray Blackmore
The Miami Project to Cure Paralysis
University of Miami
6. Why can’t axons in the CNS regenerate?
Inadequate Cell Body
Response
1. Neutralize inhibitory molecules
2. Block inhibitory signaling pathways
3. Tissue / cell transplants
≠
robust regeneration
7. Many types of neurons regenerate
Zebrafish retina
PNS
Immature CNS
8. Many types of neurons regenerate
Zebrafish retina
?
PNS
Immature CNS
9. In vivo, rodent corticospinal tract (CST) neurons lose
regenerative capacity between postnatal day 3 and 16
10. In vivo, rodent corticospinal tract (CST) neurons lose
regenerative capacity between postnatal day 3 and 16
Research strategy
1. Comparative gene profiling
2. Functional screening in culture
3. Functional gene testing in vivo
11. What CST genes change in expression between P3
and P16?
Change in CST gene expression?
>1000 genes change 3x or more
12. Candidate genes are available in large libraries
Change in CST gene expression?
>1000 genes change 3x or more
Open Biosystems Library
6,200 human genes
9,800 mouse genes
About 160 96-well plates
19. Testing gene function in vivo
Gene delivery to Dorsal hemisection
CST cell bodies
1. Knock down growth suppressive genes
2. Over-express growth promoting genes
3. Overexpress/knock down in combination
29. Acknowledgements
Vance Lemmon Jeff Goldberg
Blackmore lab Darcie Moore
John Bixby
Zimei Wang Jessica Lerch-Haner
Yania Martinez Dario Motti
Andrea Johnstone Christopher Shields
Orisley Franch Tatiana Slepak Ping Zhang
Mathew Saccino Yan Shi
University of Miami
Viral Vector Core
National Institutes of Health (NINDS, NICHD) Anthony Oliva
The Buoniconti Fund
Craig Neilsen Foundation Pingping Jia
Ralph Wilson Foundation
Wallace Coulter Foundation
Walter G. Ross Foundation
DOD