cssi/SciSciGPT-SciSciNet huggingface dataset:
Tissue-specific dynamin-1 deletion at the calyx of Held decreases short-term depression through a mechanism distinct from vesicle resupply

Dynamin is a large GTPase with a crucial role in synaptic vesicle regeneration. Acute dynamin inhibition impairs neurotransmitter release, in agreement with the protein's established role in vesicle resupply. Here, using tissue-specific dynamin-1 knockout [conditional knockout (cKO)] mice at a fast central synapse that releases neurotransmitter at high rates, we report that dynamin-1 deletion unexpectedly leads to enhanced steady-state neurotransmission and consequently less synaptic depression during brief periods of high-frequency stimulation. These changes are also accompanied by increased transmission failures. Interestingly, synaptic vesicle resupply and several other synaptic properties remain intact, including basal neurotransmission, presynaptic Ca(2+) influx, initial release probability, and postsynaptic receptor saturation and desensitization. However, acute application of Latrunculin B, a reagent known to induce actin depolymerization and impair bulk and ultrafast endocytosis, has a stronger effect on steady-state depression in cKO than in control and brings the depression down to a control level. The slow phase of presynaptic capacitance decay following strong stimulation is impaired in cKO; the rapid capacitance changes immediately after strong depolarization are also different between control and cKO and sensitive to Latrunculin B. These data raise the possibility that, in addition to its established function in regenerating synaptic vesicles, the endocytosis protein dynamin-1 may have an impact on short-term synaptic depression. This role comes into play primarily during brief high-frequency stimulation.
Toll-Like Receptor 4 Knockout Attenuates Neurogenic Inflammation and Hyperalgesia In Sickle Mice

Abstract Pain in sickle cell anemia (SCA) is accompanied by inflammation, vascular dysfunction and ischemia/reperfusion (IR) injury. We found that activated cutaneous mast cells in HbSS-BERK sickle mice release cytokines and neuropeptides and stimulate Evans blue leakage from the vasculature resulting in neurogenic inflammation and hyperalgesia (Vincent et al., 2013, Blood). Toll-like receptor 4 (TLR4) signaling stimulates mast cell activation and plays a causative role in inflammatory and neuropathic pain. Skin mast cells and spinal cords from HbSS-BERK sickle mice showed a several-fold increase in gene expression of TLR4 transcripts as compared to control mice expressing normal human hemoglobin (p Disclosures: No relevant conflicts of interest to declare.
Do Mission Statements Matter for Nonprofit Performance?: Insights from a Study of US Performing Arts Organizations

In this exploratory study, we examine whether organizational mission statement attributes make a difference to the performance of nonprofit performing arts organizations. We use text analysis to measure two semantic attributes—activity and commonality—of mission statements. We examine whether these attributes are associated with improved performance for the instrumental and expressive functions of nonprofit performing arts organizations. Our findings indicate that the mission statement attribute activity is associated with improved performance for both instrumental and expressive functions. Our analysis of nonfindings for the mission statement attribute commonality suggests that there is a need to develop and use content analysis tools tailored to nonprofit contexts.
Microbial-sized, Carboxylate-modified Microspheres as Surrogate Tracers in a Variety of Subsurface Environments: An Overview ☆

Since 1986, fluorescent carboxylate-modified polystyrene/latex microspheres (FCM) have been co-injected into aquifers along with conservative tracers and viruses, bacteria, and (or) protozoa. Use of FCM has resulted in new information about subsurface transport behaviors of microorganisms in fractured crystalline rock, karst limestone, soils, and granular aquifers. FCM have been used as surrogates for oocysts of the pathogenic protist Cryptosporidium parvum in karst limestone and granular drinking-water aquifers. The advantages of FCM in subsurface transport studies are that they are safe in tracer applications, negatively charged, easy to detect, chemically inert, and available in wide range of sizes. The limitations of FCM are that the quantities needed for some field transport studies can be prohibitively expensive and that their surface characteristics may not match the microorganisms of interest. These limitations may be ameliorated, in part by using chemically modified FCM so that their surface characteristics are a better match to that of the organisms. Also, more sensitive methods of detection may allow using smaller quantities of FCM. To assess how the transport behaviors of FCM and pathogens might compare at the field scale, it is helpful to conduct side-by-side comparisons of their transport behaviors using the geologic media and site-specific conditions that characterize the field site.
An EEG and fTCD based BCI for control

Brain-computer interfaces (BCIs) promise to promote a novel access channel for functional independence for individuals with severe speech and physical impairment (SSPI) that can occur as a result of numerous neurological diseases and injuries. Current BCI systems lack the robustness and accuracy to allow individuals with SSPI to complete tasks required for independent living (e.g. communication or navigation). We aim to develop a noninvasive hybrid BCI relying on two imaging modalities: Electroencephalography (EEG) and functional transcranial Doppler sonography (fTCD). Such hybrid BCI is expected to be sufficiently robust and accurate to be operated in a real-life environment.
EXERCISE INTOLERANCE AND PROPORTIONAL PULSE PRESSURE RESPONSE IN PATIENTS WITH CHRONIC HEART FAILURE

Background: Exercise intolerance is associated with poor outcomes in patients with heart failure (HF). The diminished peak-exercise cardiac output and impaired peripheral functions can contribute to reduced peak oxygen consumption (VO2) and higher VE/VCO2. Proportional pulse pressure (PPP), a ratio
Analysis and Compensation of Plant Degradation via Uncertainty Modeling

Abstract We present a methodology for describing time dependant plant degradation via norm-bounded uncertainty models. The purpose of this modeling is to design a robust controller for the GE16 turbofan engine that makes the closed loop system insensitive to the changes in plant parameters due to such degradation. The controller is also designed to make die system robust to engine-to-engine manufacturing variations. We begin with a (finite) set of linearized plant models generated by perturbing, in a statistical fashion, key parameters in the baseline engine model. Next, a nominal model is determined for this set along with a description of the uncertainty. The design of the controller is based on this modeling of the uncertainty and uses a standard μ synthesis procedure. Our results show that using this modeling technique along with modern robust design tools yields a controller that delivers superior performance as compared to one designed using the classical KQ method. While the design results pertain mainly to aircraft engine control, the techniques elucidated here carry over to problems where the plant to be controlled is stable and the uncertainty information is available in a similar form
Abstract #5132: The eIF4E/eIF4G interaction inhibitor 4EGI-1 augments TRAIL-induced apoptosis through DR5 induction and c-FLIP downregulation independent of inhibition of cap-dependent protein translation

Cap-dependent protein translation plays an important role in regulation of oncogenesis primarily through regulation of the expression of certain oncogenic proteins (e.g., cyclin D1 and HIF1\#945;,). Thus inhibition of cap-dependent protein translation has emerged as an attractive therapeutic strategy. The small molecule 4EGI-1 was identified as an inhibitor of cap-dependent translation initiation by disrupting eIF4E/eIF4G association through binding to eIF4E and exhibits growth-inhibitory and apoptosis-inducing activity in cancer cells. We were interested in its therapeutic effects in human lung cancer cells. 4EGI-1 as a single agent inhibited the growth and induced apoptosis of human lung cancer cells. When combined with the death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), enhanced apoptosis-induced activity was observed. In lung cancer cells, 4EGI-1 inhibited eIF4E/eIF4G interaction, reduced the levels of cyclin D1 and HIF1\#945;, both of which are regulated by a cap-dependent translation mechanism. Moreover, 4EGI-1 upregulated DR5 expression and downregulated c-FLIP levels. Small interfering RNA (siRNA)-mediated blockade of DR5 induction or enforced expression of c-FLIP abrogated 4EGI-1\#8217;s ability to enhance TRAIL-induced apoptosis, indicating that both DR5 induction and c-FLIP downregulation contribute to enhancement of TRAIL-induced apoptosis by 4EGI-1. However, inhibition of eIF4E/eIF4G interaction by eIF4E siRNA-mediated knockdown of eIF4E effectively reduced the levels of cyclin D1 and HIF1\#945;, but failed to induce DR5 expression, downregulate c-FLIP levels, and augment TRAIL-induced apoptosis. As well, the mTOR inhibitor rapamycin, which inhibits cap-dependent translation initiation, did not enhance TRAIL-induced apoptosis. Collectively, we conclude that 4EGI-1 augments TRAIL-induced apoptosis through induction of DR5 and downregulation of c-FLIP independent of inhibition of cap-dependent protein translation. (S. Fan. and Y. Li share first authorship; this work was supported by the Georgia Cancer Coalition Distinguished Cancer Scholar award, DOD grant W81XWH-04-1-0142-VITAL, NIH RO1 CA118450-01 and NIH SPORE P50 grant CA128613-01; SY Sun, and FR Khuri are Georgia Cancer Coalition Distinguished Cancer Scholars) Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5132.
Investigation of Lubricant Transfer and Lubricant Fragmentation in a Hard Disk Drive

Lubricant transfer is investigated versus temperature, local pressure change and disk velocity considering lubricant fragmentation for four different types of perfluoropolyether. Lubricant transfer and lubricant fragmentation are found to increase with temperature, local pressure change and velocity of the moving disk. The local pressure change is observed to be the most important parameter accelerating lubricant fragmentation.
Atrial Fibrillation Ablation Increases Inflammation-Chemokine Modulation Suppresses Activation of Leukocytes Isolated after Ablation.

Aims Atrial fibrillation (AF) ablation is associated with increased circulating markers of inflammation. Innate immune or inflammation pathways up-regulate mononuclear cell responses and may increase the risk for recurrent arrhythmia. Chemokines and serine protease coagulation pathways both activate innate immune responses. Here, we measured inflammatory markers in peripheral blood samples from patients after cryoballoon and/or radiofrequency pulmonary vein isolation and assessed the capacity for the inhibition of chemokine and serine protease pathways to block cell activation. Methods Markers of inflammation were measured in 55 patients immediately before and one day after AF ablation. Peripheral blood mononuclear cells (PBMCs) isolated from 19 patients were further tested for responsiveness to two anti-inflammatory proteins ex vivo using fluorescence assays and RT-qPCR analysis of gene expression. Results White blood cells (WBC), C-reactive protein, fibrinogen and troponin T levels were significantly elevated after ablation. PBMCs isolated from the circulating blood had increased activation with Phorbol 12-myristate 13-acetate. Cell activation, as measured by membrane fluidity, was blunted after treatment with a broad-spectrum chemokine modulating protein, M-T7, which interferes with chemokine/glycosaminoglycan (GAG) interactions, but not by Serp-1, a serine protease inhibitor (serpin) that targets both thrombotic and thrombolytic pathway proteases. Differential gene expression changes in the apoptotic pathway were identified with M-T7 and Serp-1. Conclusions Patients undergoing AF ablation have significantly increased inflammatory markers. Inhibition of chemokine signaling, but not serine proteases, reduced the activation of monocytes isolated from patients, in vitro. Targeting chemokines have the potential to reduce post-ablation activation of circulating leukocytes.
Iatrogenic Spondylolisthesis Following Open Lumbar Laminectomy: Case Series and Review of the Literature.

Objective To present diagnosis and surgical management of postlaminectomy spondylolisthesis in patients without preoperative instability and a review of relevant literature. Methods Medical records and radiographic studies of 105 patients who underwent first-time bilateral 1- to 4-level open laminectomies for degenerative lumbar disease at a single academic institution were reviewed. Patients who initially presented with listhesis and had additional discectomy or fusion procedures were excluded. Results Of 105 patients with laminectomies across 1–4 levels, 10 patients (9.5%; 5 men and 5 women with average age of 63.0 ± 11.2 years) developed subsequent iatrogenic spondylolisthesis at the same operative levels that required reoperation. New or worsening low back pain and lower extremity pain were reported over an average period of 19.0 ± 17.5 months postoperatively. Imaging studies showed new spondylolisthesis that was not present before the index surgery, most commonly at L4-L5 level. All patients were treated surgically with posterior instrumented fusion. The average period between the first and second surgery was 32.6 ± 19.9 months. Surgical reduction of spondylolisthesis resulted in significant clinical improvement of patients' symptoms. Conclusions In patients without overt pre-existing instability, laminectomy for lumbar stenosis can disrupt spinal stability and result in iatrogenic spondylolisthesis. The extent of decompression of the facet joints, number of levels decompressed, and preoperative disc space height can help assess the risk of postoperative spondylolisthesis. Patients who develop recurrent radiculopathy after decompressive lumbar laminectomy should be evaluated for potential iatrogenic spondylolisthesis.
Intracellular Desmoglein-2 cleavage sensitizes epithelial cells to apoptosis in response to pro-inflammatory cytokines

Desmosomal cadherins mediate intercellular adhesion and have also been shown to regulate homeostatic signaling in epithelial cells. We have previously reported that select pro-inflammatory cytokines induce Dsg2 ectodomain cleavage and shedding from intestinal epithelial cells (IECs). Dsg2 extracellular cleaved fragments (Dsg2 ECF) function to induce paracrine pro-proliferative signaling in epithelial cells. In this study, we show that exposure of IECs to pro-inflammatory cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) resulted in Dsg2 intracellular cleavage and generation of a ~55 kDa fragment (Dsg2 ICF). Dsg2 intracellular cleavage is mediated by caspase-8 and occurs prior to Dsg2 extracellular cleavage and the execution of apoptosis. Expression of exogenous Dsg2 ICF in model IECs resulted in increased sensitivity to apoptotic stimuli and apoptosis execution. Additionally, expression of the Dsg2 ICF repressed the anti-apoptotic Bcl-2 family member proteins Bcl-XL and Mcl1. Taken together, our findings identify a novel mechanism by which pro-inflammatory mediators induce modification of Dsg2 to activate apoptosis and eliminate damaged cells, while also promoting release of Dsg2 ECF that promotes proliferation of neighboring cells and epithelial barrier recovery.
Abstract 651: Autophagic Cholesterol Metabolism in Macrophages with Lysosome Dysfunction

Extensive cholesterol accumulation in human macrophages inhibits lysosome function; a key attribute of many late-stage atherosclerosis foam cells. Lipophagy (a specialized form of autophagy) delive...
Urea functionalization of ultrasound-treated biochar: A feasible strategy for enhancing heavy metal adsorption capacity.

Abstract The main objective of a series of our researches is to develop a novel acoustic-based method for activation of biochar. This study investigates the capability of biochar in adsorbing Ni(II) as a hazardous contaminant and aims at enhancing its adsorption capacity by the addition of extra nitrogen and most probably phosphorous and oxygen containing sites using an ultrasono-chemical modification mechanism. To reach this objective, biochar physically modified by low-frequency ultrasound waves (USB) was chemically treated by phosphoric acid (H3PO4) and then functionalized by urea (CO(NH2)2). Cavitation induced by ultrasound waves exfoliates and breaks apart the regular shape of graphitic oxide layers of biochar, cleans smooth surfaces, and increases the porosity and permeability of biochar’s carbonaceous structure. These phenomena synergistically combined with urea functionalization to attach the amine groups onto the biochar surface and remarkably increased the adsorption of Ni(II). It was found that the modified biochar could remove > 99% of 100 mg Ni(II)/L in only six hours, while the raw biochar removed only 73.5% of Ni(II) in twelve hours. It should be noted that physical treatment of biochar with ultrasound energy, which can be applied at room temperature for a very short duration, followed by chemical functionalization is an economical and efficient method of biochar modification compared with traditional methods, which are usually applied in a very severe temperature (>873 K) for a long duration. Such modified biochars can help protect human health from metal-ion corrosion of degrading piping in cities with aging infrastructure.
Stimulant Therapy in Acute Traumatic Brain Injury: Prescribing Patterns and Adverse Event Rates at 2 Level 1 Trauma Centers.

Background/Objective:Pharmacological stimulant therapies are routinely administered to promote recovery in patients with subacute and chronic disorders of consciousness (DoC). However, utilization ...
Evaluating sub-lethal stress from Roundup® exposure in Artemia franciscana using 1H NMR and GC-MS.

Abstract Global salinization trends present an urgent need for methods to monitor aquatic ecosystem health and characterize known and emerging stressors for water bodies that are becoming increasingly saline. Environmental metabolomics methods that combine quantitative measurements of metabolite levels and multivariate statistical analysis are powerful tools for ascertaining biological impacts and identifying potential biomarkers of exposure. We propose the use of the saltwater aquatic crustacean, Artemia franciscana, as a model organism for environmental metabolomics in saltwater ecosystems. Artemia are a good choice for ecotoxicity assays and metabolomics analysis because they have a short life cycle, their hemolymph is rich in metabolites and they tolerate a wide salinity range. In this work we explore the potential of Artemia franciscana for environmental metabolomics through exposure to the broad-spectrum herbicide, glyphosate. The LC50 for a 48 h exposure of Roundup® was determined to be 237 ± 23 ppm glyphosate in the Roundup® formulation. Artemia cysts were hatched and exposed to sub-lethal glyphosate concentrations of 1.00, 10.0, 50.0, or 100 ppm glyphosate in Roundup®. We profiled 48 h old Artemia extracts using 1H NMR and GC–MS. Dose-dependent metabolic perturbation was evident for several metabolites using univariate and multivariate analyses. Metabolites significantly affected by Roundup® exposure included aspartate, formate, betaine, glucose, tyrosine, phenylalanine, gadusol, and isopropylamine. Biochemical pathway analysis with the KEGG database suggests impairment of carbohydrate and energy metabolism, folate-mediated one-carbon metabolism, Artemia molting and development, and microbial metabolism.
Bi-compartmentalized stem cell organization of the corneal limbal niche

Stem cells exist in precise locations within tissues, yet how their organization supports tissue architecture and function is poorly understood. The limbus is the presumptive stem cell niche of the corneal epithelium. Here, we visualize the live limbus and track the activity of single stem cells in their native environment by 2-photon microscopy. We identify previously unknown niche compartments and show that long implicated slow-cycling cells form separate lineages in the outer limbus, with only local clonal dynamics. Instead, we find distinct stem cells in the pericorneal limbus to be required for corneal regeneration. Unbiased photolabeling captures their progeny exiting the niche, then moving centripetally in unison before undergoing terminal differentiation. This study demonstrates how a compartmentalized stem cell organization coordinates tissue regeneration.
Usefulness of magnetic resonance imaging to diagnose greater trochanteric-ischial impingement.

Extra-articular impingement between the femur and ischium is increasingly recognized as a cause of hip pain. The purpose of this study was to assess the diagnostic parameters for greater trochanter...
Pediatric Primary Care Relationships and Non-Urgent Emergency Department Use in Children.

Abstract Objective Non-urgent emergency department (ED) use contributes to healthcare costs and disrupts continuity of care. Factors influencing patient/guardian decision-making in non-urgent situations are poorly understood. We sought to determine the association of patient/guardian – primary care provider (PCP) relationship with non-urgent ED usage and explore related factors. Methods In an urban practice, we recruited 218 parent-child pairs and administered a survey with the PCP relationship (PDRQ-9), caregiver knowledge of office resources, and care-seeking behavior. We performed a 12-month retrospective chart review to document non-urgent ED visits. We evaluated the association of PDRQ9 and non-urgent ED usage by regression analysis. Results Mean child age was 7.0 ± 5 years, and 32.6% of children had at least one non-urgent ED visit. Mean PDRQ9 score was 39.8 ± 7.3 and was not associated with non-urgent ED use (P = .46). Lower child age (P Conclusions We did not find an association between patient-doctor relationship strength and non-urgent ED usage. Many patients/guardians were unaware of the practice's resources and selected the ED as first choice for acute, non-urgent medical scenarios. Additional work is needed to determine interventions to reduce non-urgent ED use.
Association Between Limited English Proficiency and Healthcare Access and Utilization in California

In this study, we aimed to investigate healthcare access and utilization among patients with limited English proficiency (LEP). We analyzed aggregated data from the 2018 California Health Interview Survey, a large population-based survey. Survey weighted univariate and multivariable logistic regression analyses were conducted. A total of 21,177 participants were included with 8.2% having LEP. Compared to participants with proficient English, LEP participants were less likely to have a usual place to go to when sick other than the ER or have a preventive care visit in the past year after adjusting for sociodemographic characteristics. However, LEP participants were also less likely to need to see a medical specialist and less likely to delay necessary medical care compared to English proficient participants. While patients with LEP were less likely to have access to preventative care, they were also less likely to delay necessary care.
Linking amorphous ice and supercooled liquid water

Water has fascinated humans for centuries, and, despite its central importance in biology, chemistry, and industry, we are still refining our understanding of its properties. One area of vigorous research over the last ∼50 y has been water’s supercooled liquid state—water cooled below the temperature at which ice would normally form, but maintained instead as a metastable liquid (1). Exploration of supercooled liquid water is particularly challenging because water’s propensity to crystallize increases dramatically as the temperature is decreased. One way that researchers have attempted to circumvent this issue is to study water in its amorphous solid or “glassy” states, as a way to obtain an approximate window into the supercooled liquid (2). However, a key open question in this body of work was whether the most common forms of amorphous ice (traditionally obtained by processes whose first step involves pressurizing crystalline ice at low temperature until the water molecules assume an amorphous structure; Fig. 1 A ) could be considered equivalent to a more traditional glass (most often prepared by rapidly quenching a liquid sample to low temperatures; Fig. 1 B ). Put another way, is amorphous ice actually thermodynamically connected to the liquid state, or is it, instead, just a mechanically collapsed crystal (3)? New work by Bachler et al. (4) in PNAS shows just that thermodynamic connection, by using state-of-the-art methods to prepare “hyperquenched glassy water” (HGW) by rapidly vitrifying samples of liquid water with minimal crystallization. They then performed calorimetric and X-ray diffraction experiments to demonstrate that HGW behaves identically to amorphous ices obtained by more traditional routes, strengthening the thermodynamic link between glassy water and the supercooled liquid state. Fig. 1. Amorphous ice preparation routes overlaid on a schematic metastable and glassy water phase diagram. ( A ) Crystalline ice Ih is pressurized at low temperature (solid arrow) to form HDA, which … [↵][1]1Email: tgartner{at}princeton.edu. [1]: #xref-corresp-1-1
Online gardening search activities and purchases.

Consumers have readily adopted personal computers and Internet technology with many seeking information and/or make purchases online. However, the extent to which horticultural consumers seek information and make purchases online is not well documented. A survey of 1588 consumers, representative of the United States on average, was conducted in 2004 to provide baseline information about online gardening search and purchase activities. Nearly 78% searched for gardening information at least once; of those, more than 50% of the participants searched for information at least weekly. There were differences in gardening-related searches by age and marital status, but not by region of residence, income, or gender. Nearly 50% of the study respondents made an online purchase in the year prior to the survey but only 7.4% made a gardening related purchase online. Over 50% had made a gardening-related purchase in-person. The same respondents who made in-person purchases were the individuals who made the online gardening purchases, so the Internet provided a supplemental shopping venue. There were demographic differences between those who made online gardening purchases and solely in-person gardening purchases. More males, younger and slightly less affl uent participants were more likely to make online purchases than solely in-person purchases for gardening products, supplies, and services while more females who were slightly older and more affl uent were more likely to make in-person gardening-related purchases.
Psychotherapy with Lesbian and Gay Clients from an Adult Life Course Perspective

Abstract A life course perspective of gay and lesbian adulthood enriches our understanding of clinical presentations and modifies our conception of psychotherapy. The author describes shifts in his psychotherapeutic orientation characterized by an increasing recognition of the importance of social, cultural, and historical forces that shape gay and lesbian mental health. Given the uncharted nature of many gay and lesbian lives across adulthood, existential questions about the meaning of life choices are often present in the consulting room. Therapists working with gay and lesbian clients embark on an empathic journey informed by treatment skills as well as our joint participation in a world of significant social change.
GENE AND CELLULAR TRANSPLANTATION THERAPIES FOR HUNTINGTON'S DISEASE

Publisher Summary Huntington's disease is a genetic disorder inherited in an autosomal dominant manner. The disease is caused by a mutation manifested in the IT15 or huntingtin gene located on chromosome 4. The devastating and incurable symptoms of HD include cognitive, motor and psychiatric disturbances. The cognitive symptoms often present years before the other signs and include deficits in executive functions, procedural memory and psychomotor skills. Unfortunately no efficient therapy exists that can tackle all of these symptoms while at the same time delaying or preventing cell death. Cell death in HD occurs predominantly in the projection neurons of the striatum, and it is this population of neurons that most therapies focus on protecting. However, cortical degeneration also plays a prominent role in the manifestation of deficits in higher order cognitive functions and must be targeted while designing a therapy. The discovery of toxin-induced and genetic models in both rodents and nonhuman primates has allowed for the comprehensive testing of therapies before they reach the clinic. Pharmaceutical therapies are currently the most commonly used to treat HD patients. These may be efficient at temporarily tackling the symptoms of HD but do not address the inevitable disease progression. There are a few neuroprotective therapies currently in clinical trials, but they are somewhat limited in their effectiveness. Cell replacement strategies are also in use but have been shelved in the past few years due to lack of proper funding. This review will discuss neuroprotective gene therapies and restorative cell transplantation therapies that are in use for HD research and therapy.
The Theory of Probability

The theory of probability arose from the desire of men to understand the behavior of systems that cannot entirely be controlled. More exactly, it arose from the desire of a French gambler, the Chevalier de Mere, to understand why his dice had suddenly turned against him. The Chevalier’s concern was a very practical one: he was losing money.
Appliance Energy Efficiency Labels and Standards

Refrigerators, computers, clothes washers and dryers, air conditioners, office equipment, and heating consume huge amounts of electricity. Although energy growth varies considerably among nations and economic sectors, every nation should improve the energy efficiency of its new stock of electric appliances and commercial equipment, which generally can be done at a cost far lower than building new generation facilities, before incurring the large capital expense and adverse environmental consequences of increasing generation and transmission capacity. Appliance efficiency labels that accurately inform consumers of the electricity the appliance will require, and appliance efficiency standards that set minimum efficiency requirements for appliances in the marketplace are among the most inexpensive and effective means of improving the efficiency of residential and commercial electricity use. Private manufacturers will innovate and compete within the government set ground rules. Government can also provide incentives to industry to improve appliance efficiency beyond minimum standards. As greater product efficiency is realized, the government could ratchet the standards to the higher level achieved by the innovation. This iterative process can transform the market to one that drives substantial efficiency improvements.This chapter will offer an overview of the process and issues involved in drafting appliance efficiency and labeling laws, provide examples of typical legislative language and references to on-line resources with detailed information, analytical templates and supporting databases for drafting appliance efficiency legislation and regulations.
AltitudeOmics: pulmonary gas exchange efficiency in humans with and without a PFO following 16 days of acclimatization to 5,260 m (885.2)

A PFO is a source of intracardiac shunt causing impaired pulmonary gas exchange efficiency, defined by an increased alveolar-to-arterial PO2 difference (AaDO2). Prior studies investigating human acclimatization to high altitude (HA) have not investigated differences between subjects with a patent foramen ovale (PFO+) and those without (PFO−), yet prevalence of PFO in the general population is ~40%. Twenty-one (11 PFO+) healthy lowlanders were studied at rest and at 70, 100, 130, and 160W of cycle ergometer exercise at sea level (SL), in acute hypoxia at 5,260 m (ALT1), and after 16 days of acclimatization to 5,260 m (ALT16). Exercise data were compared at the highest iso-workload, within an individual, achieved at SL, ALT1 and ALT16. During exercise at SL, PFO+ subjects demonstrated a wider AaDO2 compared to PFO− subjects, however on ALT1 the AaDO2 was not different between PFO− and PFO+ subjects. At ALT16, unlike PFO− subjects, AaDO2 in PFO+ subjects was not different from ALT1. Surprisingly, at ALT16 th...
Case-Control Studies

The case-control study examines the association between disease and potential risk factors by taking separate samples of diseased cases and of controls at risk of developing disease. Information may be collected for both cases and controls on genetic, social, behavioral, environmental or other determinants of disease risk. The basic study design has a long history, extending back at least to Guy’s 1843 comparison of the occupations of men with pulmonary consumption to the occupations of men having other diseases (Lilienfeld and Lilienfeld 1979). Beginning in the 1920’s, it was used to link cancer to environmental and hormonal exposures. Broders (1920) discovered an association between pipe smoking and lip cancer; Lane-Claypon (1926), who selected matched hospital controls, investigated the relationship between reproductive experience and female breast cancer; and Lombard and Doering (1928) related pipe smoking to oral cancer. The publication in 1950 of three reports on the association between cigarette smoking and lung cancer generated enormous interest in case-control methodology as well as bitter criticism (Levin et al. 1950; Wynder and Graham 1950; Doll and Hill 1950). The landmark study of Doll and Hill (1950, 1952), in particular, inspired future generations of epidemiologists to use this methodology. It remains to this day a model for the design and conduct of case-control studies, with excellent suggestions on how to reduce or eliminate selection, interview and recall bias.
Dietary supplementation with white button mushroom augments the protective immune response to Salmonella vaccine in mice

We previously showed that dietary white button mushrooms (WBM) enhance natural killer cell activity and in vitro WBM promotes maturation and function of dendritic cells (DC). The current study inve...
A framework for evaluating storage system security

There are a variety of ways to ensure the security of data and the integrity of data transfer, depending on the set of anticipated attacks, the level of security desired by data owners, and the level of inconvenience users are willing to tolerate. Current storage systems secure data either by encrypting data on the wire, or by encrypting data on the disk. These systems seem very different, and currently there are no common parameters for comparing them. In this paper we propose a framework in which both types of systems can be evaluated along the security and performance axes. In particular, we show that all of the existing systems merely make different trade-offs along a single continuum and among a set of related security primitives. We use a trace from a time-sharing UNIX server used by a medium-sized workgroup to quantify the costs associated with each of these secure storage systems. We show that encrypt-on-disk systems offer both increased security and improved performance over encrypt-on-wire in the traced environment.
Posttranslational modifications of the beta subunit of a cryptomonad phycoerythrin. Sites of bilin attachment and asparagine methylation.

Abstract Determination of the partial amino acid sequence of the beta subunit of cryptomonad strain CBD phycoerythrin 566 established the nature, locations, and modes of attachment of the three bilin prosthetic groups and revealed a site of posttranslational methylation. Isolation of peptides cross-linked by a phycobiliviolin led to an unambiguous assignment of two thioether linkages, from residues beta-Cys-50 and beta-Cys-61 to this bilin. Two bilins were attached through single thioether linkages, a phycobiliviolin at beta-Cys-158 and a phycoerythrobilin at beta-Cys-82 (the residue numbering is that for B-phycoerythrin; Sidler, W., Kumpf, B., Suter, F., Morisset, W., Wehrmeyer, W., and Zuber, H. (1985) Biol. Chem. Hoppe-Seyler 366, 233-244). The partial sequences (99 residues) established for phycoerythrin 566 beta subunit showed a 79% identity with that of the red algal Porphyridium cruentum B-phycoerythrin beta subunit. A particularly remarkable finding is that the unique methylasparagine residue at position beta-72, highly conserved in cyanobacterial and red algal phycobiliproteins (Klotz, A. V., and Glazer, A. N. (1987) J. Biol. Chem. 262, 17350-17355), is also present at beta-72 in the cryptomonad phycoerythrin. Comparison of the locations of donor and acceptor bilins in cryptomonad phycoerythrin with those found for cyanobacterial and red algal phycobiliproteins showed different favored pathways of energy migration in the cryptomonad protein.
Assessment of Older Adults

The psychological assessment of older adults poses challenges for the clinician comparable to those faced by such eminent sleuths as Hercule Poirot, Jessica Fletcher, and even Sherlock Holmes. Indeed, anyone drawn to murder mysteries would find the assessment of older adults an equally challenging, intriguing, and provocative undertaking. The thorough assessment of an older adult has many of the characteristics of a murder investigation, requiring consideration of the intimate interplay of physical, psychological, and environmental variables. Any investigator or clinician worthy of his or her salt would, for example, question everyone familiar with the behavior of the individual of interest (never trusting one source), directly inspect the environment in which behaviors of interest occurred, employ the most accurate, reliable, and valid measurement instruments, gather clues resulting from the interactions of the target individual with the environment, obtain descriptions or directly observe the interaction of the target individual with significant others, determine who gained and who suffered as a consequence of the individual’s behavior, assemble clues (assessment results) from multiple sources to establish convergent validity for hypotheses, and systematically test hypotheses until a satisfactory and empirically defensible conclusion could be reached. Though the assessment of older adults and the investigation of a murder share principles and procedures, they part company with the consideration of their functions, notwithstanding the analogous relationship between a murderer and a disease or disorder.
Variance entropy: a method for characterizing perceptual awareness of visual stimulus

Entropy, as a complexity measure, is a fundamental concept for time series analysis. Among many methods, sample entropy (SampEn) has emerged as a robust, powerful measure for quantifying complexity of time series due to its insensitivity to data length and its immunity to noise. Despite its popular use, SampEn is based on the standardized data where the variance is routinely discarded, which may nonetheless provide additional information for discriminant analysis. Here we designed a simple, yet efficient, complexity measure, namely variance entropy (VarEn), to integrate SampEn with variance to achieve effective discriminant analysis. We applied VarEn to analyze local field potential (LFP) collected from visual cortex of macaque monkey while performing a generalized flash suppression task, in which a visual stimulus was dissociated from perceptual experience, to study neural complexity of perceptual awareness. We evaluated the performance of VarEn in comparison with SampEn on LFP, at both single and multiple scales, in discriminating different perceptual conditions. Our results showed that perceptual visibility could be differentiated by VarEn, with significantly better discriminative performance than SampEn. Our findings demonstrate that VarEn is a sensitive measure of perceptual visibility, and thus can be used to probe perceptual awareness of a stimulus.
Optimization of Technical and Operational Characteristics of a CAES Facility in West Texas to Balance Intermittent Wind Power

An optimization model was created to optimize the input power capacity and storage capacity relative to the output power capacity of a compressed air energy storage (CAES) facility in the Electric Reliability Council of Texas (ERCOT) grid. Historical electricity and non-spinning reserve prices were used to calculate the economic feasibility of CAES in each of the zones in ERCOT. The analysis found that with perfect knowledge of future prices a CAES facility would be economically attractive over the period of years considered, and the non-spinning reserve ancillary service market provided a substantial contribution to the overall revenue of the facility. Optimal input power capacity for the entire period of 2002 through 2010 was found to be about one-quarter of the output capacity in the Houston, South, and North zones in ERCOT and one-half the output power capacity in the West zone in ERCOT. Optimal storage capacity was found to be about 17 hours in the Houston, South, and North zones and 31 hours in the West zone. Optimal values for individual years varied significantly, as did revenues. The negative electricity prices that have occurred historically in the West zone are the consequence of wind generators and lack of transmission capacity to export electricity; this effect gives CAES greater opportunity to perform price arbitrage and improves the economics of such a facility.Copyright © 2011 by ASME
Genetic Determinants of HIV-1 Infection and Its Manifestations

The human immunodeficiency virus type 1 (HIV-1), which has become pandemic within a single generation, has encountered an immune system in which genetically encoded elements have evolved gradually under different environmental pressures in diverse populations. Important heritable differences in genes that alter susceptibility to HIV-1 infection or the rate of deterioration of immunity, or both, have been discovered in cohorts carefully defined for intensity of exposure to the virus, viral subtype characteristics, and onset and course of infection. For the highly polymorphic human leukocyte antigen (HLA) antigen processing and presenting system, the principle that small contributions of multiple interactive HLA marker combinations (primarily in the class I pathway) significantly modulate the course of HIV-1 infection has now been confirmed in several independently evaluated groups of patients. Variants of HLA genes probably also play some role in the acquisition of infection by the various routes of transmission. Genes for an elaborate set of circulating chemokine molecules and their cell-surface receptors clearly regulate cell attachment and penetration of HIV. Certain allelic forms of one, the CCR5 gene, alter susceptibility to infection and the rate of progression of disease; in the homozygous state, a deleted form (Delta32 CCR5) strongly protects against infection, and in infected heterozygotes, it slows the disease process somewhat. Mutants in genes of other chemokine system components further differentiate the response to infection, and frequencies of these forms vary between and within races. Work relating additional genetic markers to HIV infection or disease is at earlier stages. Dissecting the effects of multiple variants in complex gene systems will clearly require organized comprehensive approaches in considerably larger populations than have typically been assembled.
A Novel Technique for Peripheral Nerve Repair

OBJECTIVE To evaluate a novel technique for the repair of neural deficits using a single fascicle to bridge an injury in the rat sciatic nerve. STUDY DESIGN Twenty-four male Lewis rats were divided into four groups as follows: group 1 (control group), 1.5-cm deficit without repair; group 2, conventional epineural repair with autografts (100% diameter); group 3, nerve repair with large single autograft fascicle (50% diameter); and group 4, nerve repair with small single autograft fascicle (25% diameter). METHODS Nerve regeneration was evaluated at 3, 6, and 12 weeks by somatosensory evoked potential (SSEP) evaluation and standardized pin-prick and toe-spread tests. Nerve samples were harvested at 12 weeks and stained with toluidine blue to assess the total number of myelinated axons, axon area, and myelin sheath thickness. RESULTS In group I, the pin-prick and toe-spread tests showed no response at 3, 6, and 12 weeks. Rats in groups 3 and 4 demonstrated significantly better pin-prick test results and a trend toward better toe-spread test responses compared with conventional-repair animals. The SSEP evaluations displayed nondiagnostic waves in rats in group 1 rats. There was no evidence that the other surgery groups differed significantly in median SSEP latencies. Histological evaluation revealed fibrosis in rats in group 1 rats and a significantly higher median number of axons and myelin thickness in the small single fascicle (1296 axons and 4.22 microm, respectively) and large fascicle (2682 axons and 4.62 microm, respectively) groups compared with the conventional autograft group (630 axons and 2.93 microm, respectively). The small fascicle group had a significantly greater mean axon area (58.59 micro m2) than the large fascicle (29.66 micro m2) and conventional autograft (25.35 micro m2) groups. CONCLUSIONS Peripheral nerve repair using a single fascicle graft resulted in better functional recovery and morphometric outcome without a significant difference in electrophysiological status compared with conventional nerve repair. This technique may provide expanded sources of nerve autografts and alleviate the morbidity of harvesting peripheral nerves from multiple sites for individuals with extensive peripheral nerve injuries.
A historical view of germanium as an infrared window material

The story of germanium's development as an infrared dome and window material exemplifies the manner in which the complementary efforts of industry, academia and government can work together to solve scientific and technical challenges. Germanium is one of a few materials which have been used for infrared transparent windows in both the long-wave 8-12 micron region, as well as the mid-wave 3-5 micron region. Due to its legacy as one of the first commercial semiconductors, germanium became available in high purity as a bulk commodity. This paper will examine the history of how germanium came to be used as an infrared window and what enabling technologies have supported its use.
Putin's "Southern Strategy": Dmitriy Kozak and the Dilemmas of Recentralization

Putin recentralized policy-making and political power through administrative reforms that reduced the power of the regions and shifted that power to the center. Sent to try to manage Russia's Southern Federal District, which includes the particularly troubled republics of the North Caucasus, and then as the Minister for Regional Development, Dmitriy Kozak developed a series of recommendations that, in effect, rejected Putin's recentralization. This article draws on newspaper coverage, World Bank and human rights organizations' documents, and the political science literature to explore the impact that "going South" had on Kozak's policy prescriptions. Chechnya is considered as an approach quite different from the one Kozak sought to put in place.