1,916 research outputs found
Cellular excitability and the regulation of functional neuronal identity: from gene expression to neuromodulation
The intrinsic properties of a neuron determine the translation of synaptic input to axonal output. It is this input– output relationship that is the heart of all nervous system activity. As such, the overall regulation of the intrinsic excitability of a neuron directly determines the output of that neuron at a given point in time, giving the cell a unique “functional identity.” To maintain this distinct functional output, neurons must adapt to changing patterns of synaptic excitation. These adaptations are essential to prevent neurons from either falling silent as synaptic excitation falls or becoming saturated as excitation increases. In the absence of stabilizing mechanisms, activity-dependent plasticity could drive neural activity to saturation or quiescence. Furthermore, as cells adapt to changing patterns of synaptic input, presumably the overall balance of intrinsic conductances of the cell must be maintained so that reliable output is achieved (Daoudal and Debanne, 2003; Turrigiano and Nelson, 2004; Frick and Johnston, 2005). Although these regulatory phenomena have been well documented, the molecular and physiological mechanisms involved are poorly understood
Probing Wolf-Rayet Winds: Chandra/HETG X-Ray Spectra of WR 6
With a deep Chandra/HETGS exposure of WR 6, we have resolved emission lines
whose profiles show that the X-rays originate from a uniformly expanding
spherical wind of high X-ray-continuum optical depth. The presence of strong
helium-like forbidden lines places the source of X-ray emission at tens to
hundreds of stellar radii from the photosphere. Variability was present in
X-rays and simultaneous optical photometry, but neither were correlated with
the known period of the system or with each other. An enhanced abundance of
sodium revealed nuclear processed material, a quantity related to the
evolutionary state of the star. The characterization of the extent and nature
of the hot plasma in WR 6 will help to pave the way to a more fundamental
theoretical understanding of the winds and evolution of massive stars.Comment: Accepted by the Astrophysical Journa
Differences in hospital glycemic control and insulin requirements in patients recovering from critical illness and those without prior critical illness
INTRODUCTION: Hospital patients recovering from critical illness on general floors often receive insulin therapy based on protocols designed for patients admitted directly to general floors. The objective of this study is to compare glycemic control and insulin dosing in patients recovering from critical illness and those without prior critical illness. METHODS: Medical record review of blood glucose measurements and insulin dosing in 25 patients under general ward care while transitioning from the intensive care unit (transition group) and 25 patients admitted directly to the floor (direct floor group). RESULTS: Average blood glucose did not differ significantly between groups (transition group 9.49 mmol/L, direct floor group 9.6 mmol/L; P = 0.83). Significant differences in insulin requirements were observed between groups with average daily doses of 55.9 units in patients transitioning from the intensive care unit (ICU) versus 25.6 units in the direct floor group (P = 0.004). CONCLUSIONS: Patients recovering from critical illness required significantly larger doses of insulin than those patients admitted directly to the floor. Managing insulin therapy in patients transitioning from the ICU may require greater insulin doses
Characterization and Comparison of Human Glioblastoma Models
AbstractGlioblastoma (GBM) is one of the deadliest cancers. Treatment options are limited, and median patient survival is only several months. Translation of new therapies is hindered by a lack of GBM models that fully recapitulate disease heterogeneity. Here, we characterize two human GBM models (U87-luc2, U251-RedFLuc). In vitro, both cell lines express similar levels of luciferase and show comparable sensitivity to temozolomide and lapatinib exposure. In vivo, however, the two GBM models recapitulate diferent aspects of the disease. U87-luc2 cells quickly grow into large, well-demarcated tumors; U251-RedFLuc cells form small, highly invasive tumors. Using a new method to assess GBM invasiveness based on detecting tumor-specifc anti-luciferase staining in brain slices, we found that U251-RedFLuc cells are more invasive than U87-luc2 cells. Lastly, we determined expression levels of ABC transporters in both models. Our fndings indicate that U87-luc2 and U251-RedFLuc GBM models recapitulate diferent aspects of GBM heterogeneity that need to be considered in preclinical research
On the AC spectrum of one-dimensional random Schroedinger operators with matrix-valued potentials
We consider discrete one-dimensional random Schroedinger operators with
decaying matrix-valued, independent potentials. We show that if the l^2-norm of
this potential has finite expectation value with respect to the product measure
then almost surely the Schroedinger operator has an interval of purely
absolutely continuous (ac) spectrum. We apply this result to Schroedinger
operators on a strip. This work provides a new proof and generalizes a result
obtained by Delyon, Simon, and Souillard.Comment: (1 figure
Patterns of Neoplasia in c-Mos Transgenic Mice and Their Relevance to Multiple Endocrine Neoplasia
We have previously described a neurological phenotype for transgenic mice carrying the c-Mos proto-oncogene. Pheochromocytomas and C-cell thyroid neoplasms occur in these transgenic lines in patterns that are similar to those seen in multiple endocrine neoplasia type 2 (MEN 2). Characterization of the pathological lesions via immunohistochemistry underscores similarities between MEN 2 and these transgenic mice. When transgenic mice that do not display the MEN 2 phenotype are crossed to a different background, the progeny display the MEN 2 phenotype. Thus the interaction of the background with the transgene is such that it can suppress tumor information. This observation bears special relevance to the human syndrome in that this model system may be used to study the question of penetrance of phenotype
Spin and interaction effects on charge distribution and currents in one-dimensional conductors and rings within the Hartree-Fock approximation
Using the self--consistent Hartree-Fock approximation for electrons with spin
at zero temperature, we study the effect of the electronic interactions on the
charge distribution in a one-dimensional continuous ring containing a single
scatterer. We reestablish that the interaction suppresses the decay
of the Friedel oscillations. Based on this result, we show that in an infinite
one dimensional conductor containing a weak scatterer, the current is totally
suppressed because of a gap opened at the Fermi energy. In a canonical ensemble
of continuous rings containing many scatterers, the interactions enhance the
average and the typical persistent current.Comment: 5 pages, 4 figure
Data and safety monitoring in social behavioral intervention trials: the REACH II experience
Background Psychosocial and behavioral interventions trials targeting a broad range of complex social and behavioral problems such as smoking, obesity and family caregiving have proliferated in the past 30 years. At the same time the use of Data and Safety Monitoring Boards (DSMBs) to monitor the progress and quality of intervention trials and the safety of study participants has increased substantially. Most of the existing literature and guidelines for safety monitoring and reporting of adverse events focuses on medical interventions. Consequently, there is little guidance for investigators conducting social and behavior trials.
Purpose This paper summarizes how issues associated with safety monitoring and adverse event reporting were handled in the Resources for Enhancing Alzheimer\u27s Caregiver Health (REACH II) program, a multi-site randomized clinical trial, funded by the National Institutes on Aging (NIA) and the National Institutes of Nursing Research (NINR), that tested the efficacy of a multicomponent social/behavioral intervention for caregivers of persons with Alzheimer\u27s disease.
Methods A task force was formed to define adverse events for the trial and protocols for reporting and resolving events that occurred. The task force conducted a review of existing polices and protocols for data and safety monitoring and adverse event reporting and identified potential risks particular to the study population. An informal survey regarding data and safety monitoring procedures with investigators on psychosocial intervention trials was also conducted.
Results Two categories of events were defined for both caregivers and patients; adverse events and safety alerts. A distinction was also made between events detected at baseline assessment and those detected post-randomization. Standardized protocols were also developed for the reporting and resolution of events that occurred and training of study personnel. Results from the informal survey indicated wide variability in practices for data safety and monitoring across psychosocial intervention trials. Conclusions Overall, the REACH II experience demonstrates that existing guidelines regarding safety monitoring and adverse event reporting pose unique challenges for social/behavioral intervention trials. Challenges encountered in the REACH II program included defining and classifying adverse events, defining resolution of adverse events and attributing causes for events that occurred. These challenges are highlighted and recommendations for addressing them in future studies are discussed
Differences in Hospital Glycemic Control and Insulin Requirements in Patients Recovering From Critical Illness and Those Without Prior Critical Illness
INTRODUCTION: Hospital patients recovering from critical illness on general floors often receive insulin therapy based on protocols designed for patients admitted directly to general floors. The objective of this study is to compare glycemic control and insulin dosing in patients recovering from critical illness and those without prior critical illness. METHODS: Medical record review of blood glucose measurements and insulin dosing in 25 patients under general ward care while transitioning from the intensive care unit (transition group) and 25 patients admitted directly to the floor (direct floor group). RESULTS: Average blood glucose did not differ significantly between groups (transition group 9.49 mmol/L, direct floor group 9.6 mmol/L; P = 0.83). Significant differences in insulin requirements were observed between groups with average daily doses of 55.9 units in patients transitioning from the intensive care unit (ICU) versus 25.6 units in the direct floor group (P = 0.004). CONCLUSIONS: Patients recovering from critical illness required significantly larger doses of insulin than those patients admitted directly to the floor. Managing insulin therapy in patients transitioning from the ICU may require greater insulin doses
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