223 research outputs found
A Study of Drift Mobility in Neutron Irradiated n-Type Germanium
With the advent of the transistor in the late 1940\u27s have come an entirely new field of engineering and a greatly renewed interest in solid state physics. This paper will be concerned in general with the electrical properties of these materials, and specifically drift mobility of the minority carriers in n-type germanium. The minority carrier in n-type material is the hole. The definition of drift mobility is: the mean carrier velocity per unit electric field
Solid state cryogenic temperature sensor Final report
Gallium arsenide cryogenic temperature sensor developmen
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Regulatory logic of cellular diversity in the nervous system
During nervous system development, thousands of distinct cell types are generated and assembled into complex circuits that control all aspects of animal cognition and behavior. Understanding what these diverse cells are, how they are generated, and what they do in the context of circuits and behavior form the fundamental efforts of the field of neuroscience. In this thesis, I investigate how the genomic organization of regulatory elements informs specific patterns of gene expression in the nervous system. In particular, I examine how distinct combinations of transcription factors interpret information encoded in the genome to control global gene expression programs in a cell-type-specific manner.
In Chapter Two, I describe the establishment of a developmentally inspired transcriptional programming system to generate spinal and cranial motor neurons directly from mouse embryonic stem cells. Programmed motor neurons acquire general characteristics that mirror their in vivo counterparts, providing a robust system for studying cell fate specification in the nervous system. Combinatorial expression of cell-type-specific programming factors informs context-dependent enhancer binding and acquisition of appropriate cell-type-specific molecular and functional properties.
In Chapter Three, I take advantage of this robust, experimentally accessible system to probe the chromatin-level organization and regulatory principles controlling specificity of motor neuron gene expression programs. Motor neuron genes are controlled by multiple distantly distributed enhancer constellations stretched across large regulatory domains. Using this motor neuron specification model, I discovered a unique regulatory organization controlling gene expression in the nervous system, whereby neuronal genes are controlled from uniquely complex regulatory domains acting over large distances.
In Chapter Four, I extrapolate on the insights gained from studying motor neurons at a single point in time to investigate the dynamics of the regulatory environment during neuronal maturation. We demonstrate that enhancers are highly dynamic even after postmitotic specification. The dynamic nature of enhancers is dependent on combinatorial binding with new transcriptional cofactors.
Overall, my results suggest that neuronal gene expression programs within a single cell type are regulated in a highly dynamic fashion by a complex set of enhancers. I propose that during development the immense cellular complexity of the nervous system is established and maintained by correspondingly complex repertoire of enhancers
Why we must provide better support for Pakistan\u27s female frontline health workers
Svea Closser and Rashid Jooma argue that achieving polio eradication and strengthening Pakistan\u27s health system must focus not just on international engagement but also on local partnerships with Lady Health Workers and other ground-level staff. Please see later in the article for the Editors\u27 Summary
Transforming Information Literacy Through Librarian/Course Instructor Collaboration: A Case Study
This paper looks at librarian/course instructor collaboration in higher education and draws specific lessons from the two-year experience of a librarian embedded into an advanced college writing class. The case study pays particular attention to how collaboration influences students\u27 development of research and writing skills and attitudes, and the instructional design of the course
Tandem Intramolecular Nicholas and Pauson-Khand Reactions for the Synthesis of Tricyclic Oxygen-Containing Heterocycles
Simple acyclic enynes can be easily converted into tricyclic ethers upon treatment with Co2(CO)8followed by Nicholas and Pauson−Khand reactions. Tricyclic [5,8,5]- and [5,7,5]-systems can be prepared in high overall yields in only seven synthetic steps
Measuring the health systems impact of disease control programmes: a critical reflection on the WHO building blocks framework.
BACKGROUND: The WHO health systems Building Blocks framework has become ubiquitous in health systems research. However, it was not developed as a research instrument, but rather to facilitate investments of resources in health systems. In this paper, we reflect on the advantages and limitations of using the framework in applied research, as experienced in three empirical vaccine studies we have undertaken. DISCUSSION: We argue that while the Building Blocks framework is valuable because of its simplicity and ability to provide a common language for researchers, it is not suitable for analysing dynamic, complex and inter-linked systems impacts. In our three studies, we found that the mechanical segmentation of effects by the WHO building blocks, without recognition of their interactions, hindered the understanding of impacts on systems as a whole. Other important limitations were the artificial equal weight given to each building block and the challenge in capturing longer term effects and opportunity costs. Another criticism is not of the framework per se, but rather how it is typically used, with a focus on the six building blocks to the neglect of the dynamic process and outcome aspects of health systems.We believe the framework would be improved by making three amendments: integrating the missing "demand" component; incorporating an overarching, holistic health systems viewpoint and including scope for interactions between components. If researchers choose to use the Building Blocks framework, we recommend that it be adapted to the specific study question and context, with formative research and piloting conducted in order to inform this adaptation. SUMMARY: As with frameworks in general, the WHO Building Blocks framework is valuable because it creates a common language and shared understanding. However, for applied research, it falls short of what is needed to holistically evaluate the impact of specific interventions on health systems. We propose that if researchers use the framework, it should be adapted and made context-specific
High Resolution Mapping of Enhancer-Promoter Interactions
RNA Polymerase II ChIA-PET data has revealed enhancers that are active in a profiled cell type and the genes that the enhancers regulate through chromatin interactions. The most commonly used computational method for analyzing ChIA-PET data, the ChIA-PET Tool, discovers interaction anchors at a spatial resolution that is insufficient to accurately identify individual enhancers. We introduce Germ, a computational method that estimates the likelihood that any two narrowly defined genomic locations are jointly occupied by RNA Polymerase II. Germ takes a blind deconvolution approach to simultaneously estimate the likelihood of RNA Polymerase II occupation as well as a model of the arrangement of read alignments relative to locations occupied by RNA Polymerase II. Both types of information are utilized to estimate the likelihood that RNA Polymerase II jointly occupies any two genomic locations. We apply Germ to RNA Polymerase II ChIA-PET data from embryonic stem cells to identify the genomic locations that are jointly occupied along with transcription start sites. We show that these genomic locations align more closely with features of active enhancers measured by ChIP-Seq than the locations identified using the ChIA-PET Tool. We also apply Germ to RNA Polymerase II ChIA-PET data from motor neuron progenitors. Based on the Germ results, we observe that a combination of cell type specific and cell type independent regulatory interactions are utilized by cells to regulate gene expression.National Institutes of Health (U.S.) (Grant 1U01HG007037
Treatment of Alprazolam withdrawal with chlordiazepoxide substitution and taper
We describe the first case series (n = 6) of using chlordiazepoxide to accomplish a rapid, well-tolerated withdrawal from alprazolam. After abruptly discontinuing alprazolam, we substituted a 50-mg dose of chlordiazepoxide for each 1 mg of alprazolam (except for one elderly patient where we substituted 25 mg) and gave additional chlordiazepoxide doses (25-50 mg every 4-6 hours) as needed for the first 1-2 days of hospitalization. With this approach, the mean "substitution ratio" of chlordiazepoxide to alprazolam was 86 to 1. We then tapered chlordiazepoxide by an average of 10% each day over a 7- to 14-day period according to the symptoms manifested and tolerated by individual patients. No seizures or other serious side effects occurred. Incomplete cross- dependence, as described elsewhere in the literature, was not observed. The rapidity and familiarity of the method are advantages for inpatient units, but careful titration of dosage, diagnostic clarity, and extended follow-ups are necessary when applying this approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31476/1/0000398.pd
Polio eradication and health systems in Karachi: Vaccine refusals in context
Community and health worker engagement will be key to polio eradication in Karachi, Pakistan. In this study, the authors conducted participant observation, interviews, and a document review in SITE Town, Karachi, an area that in recent years has harbored poliovirus. SITE’s diverse population includes large numbers of internally displaced persons who are disproportionately affected by polio and are more likely than other populations to refuse the polio vaccine. Vaccine acceptance and worker motivation in SITE Town were shaped by the discrepancy in funding and attention for polio eradication campaigns as compared with routine services. Parental vaccine refusals stemmed from a distrust of government and international actors that provided few services but administered polio vaccine door-to-door every month. Addressing this discrepancy could therefore be key to eliminating polio. The authors suggest short-term improvements to routine immunization and sanitation in key polio endemic areas, coupled with a longterm focus on sustainable improvements to routine immunization and broader health services
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