gebhart/patrepeval huggingface dataset:
Dominant-Negative Mutants Identify a Role for Girk Channels in D3 Dopamine Receptor-Mediated Regulation of Spontaneous Secretory Activity (2000)

The human D3 dopamine receptor can activate G-protein-coupled inward rectifier potassium channels (GIRKs), inhibit P/Q-type calcium channels, and inhibit spontaneous secretory activity in AtT-20 neuroendocrine cells (Kuzhikandathil, E.V., W. Yu, and G.S. Oxford. 1998. Mol. Cell. Neurosci. 12:390-402; Kuzhikandathil, E.V., and G.S. Oxford. 1999. J. Neurosci. 19:1698-1707). In this study, we evaluate the role of GIRKs in the D3 receptor-mediated inhibition of secretory activity in AtT-20 cells. The absence of selective blockers for GIRKs has precluded a direct test of the hypothesis that they play an important role in inhibiting secretory activity. However, the tetrameric structure of these channels provides a means of disrupting endogenous GIRK function using a dominant negative approach. To develop a dominant-negative GIRK mutant, the K(+) selectivity amino acid sequence -GYG- in the putative pore domain of the human GIRK2 channels was mutated to -AAA-, -GLG-, or -GFG-. While the mutation of -GYG- to -GFG- did not affect channel function, both the -AAA- and -GLG- GIRK2 mutants were nonfunctional. This suggests that the aromatic ring of the tyrosine residue rather than its hydroxyl group is involved in maintaining the pore architecture of human GIRK2 channels. When expressed in AtT-20 cells, the nonfunctional AAA-GIRK2 and GLG-GIRK2 acted as effective dominant-negative mutants and significantly attenuated endogenous GIRK currents. Furthermore, these dominant-negative mutants interfered with the D3 receptor-mediated inhibition of secretion in AtT-20 cells, suggesting they are centrally involved in the signaling pathway of this secretory response. These results indicate that dominant-negative GIRK mutants are effective molecular tools to examine the role of GIRK channels in vivo.
The Fungal Photosensitizer Cercosporin and Its Role in Plant Disease (1987)

Cercosporin is a photosensitizing toxin produced by fungal plant pathogens in the genus Cercospora. Cercosporin produces singlet oxygen and superoxide when irradiated by light, and damages plants by causing a peroxidation of the membrane lipids. This membrane damage leads to a loss in membrane fluidity, leakage of nutrients, and rapid death of the plant cell. Cercosporin is toxic to mice and bacteria in addition to plants, and attempts to select plant cells in vitro for resistance to cercosporin have not been successful. A large number of fungal species, however, are resistant to cercosporin. Carotenoids and the fungal cell wall appear to play a critical role in the resistance of fungi to cercosporin.
Cultured blood T‐cell responses predict anti‐<scp>TNF</scp> therapy response in patients with ulcerative colitis (2015)

The effects of anti-TNF on cultured blood T cells, obtained before therapy started, predict treatment outcome in patients with UC.
Abstract: Extended Abstract for Evaluating Asynchrony in Gibraltar RAID's GPU Reed-Solomon Coding Library (2012)

GPU has been utilized for Reed Solomon coding tasks for arbitrary (k+n) RAID system. In this project, we apply the asynchronous design with CUDA in order to run multiple coding tasks simultaneously. Results show significant performance boosts for small block coding tasks by concurrent kernels.
Automated In-Process Inspection System for AFP Machines (2015)

<div class="section abstract"><div class="htmlview paragraph">In many existing AFP cells manual inspection of composite plies accounts for a large percentage of production time. Next generation AFP cells can require an even greater inspection burden. The industry is rapidly developing technologies to reduce inspection time and to replace manual inspection with automated solutions. Electroimpact is delivering a solution that integrates multiple technologies to combat inspection challenges. The approach integrates laser projectors, cameras, and laser profilometers in a comprehensive user interface that greatly reduces the burden on inspectors and decreases overall run time.</div><div class="htmlview paragraph">This paper discusses the implementation of each technology and the user interface that ties the data together and presents it to the inspector.</div></div>
Two-Dimensional Transition Metal Dichalcogenide Alloys: Stability and Electronic Properties (2012)

Using density-functional theory calculations, we study the stability and electronic properties of single layers of mixed transition metal dichalcogenides (TMDs), such as MoS2xSe2(1-x), which can be referred to as two-dimensional (2D) random alloys. We demonstrate that mixed MoS2/MoSe2/MoTe2 compounds are thermodynamically stable at room temperature, so that such materials can be manufactured using chemical-vapor deposition technique or exfoliated from the bulk mixed materials. By applying the effective band structure approach, we further study the electronic structure of the mixed 2D compounds and show that general features of the band structures are similar to those of their binary constituents. The direct gap in these materials can continuously be tuned, pointing toward possible applications of 2D TMD alloys in photonics.
The chemokine growth-regulated oncogene 1 (Gro-1) links RAS signaling to the senescence of stromal fibroblasts and ovarian tumorigenesis (2006)

Epithelial-stromal interactions play a critical role in tumor initiation and progression; cancer-associated stroma, but not normal stroma, is known to be tumor-promoting. However, the molecular signal used by epithelial cancer cells to reprogram normal stroma to a tumorigenic stroma is not known. Here, we present evidence to suggest that the chemokine growth-regulated oncogene 1 (Gro-1) may be one such signaling molecule. We showed that the expression of Gro-1 is activated by RAS and is vital for cell survival and the malignant transformation of ovarian epithelial cells. Surprisingly, we found that Gro-1 is a potent inducer of senescence in stromal fibroblasts and that this effect depends on functional p53. Senescent fibroblasts induced by Gro-1 can promote tumor growth whereas abrogation of senescence through immortalization results in loss of such tumor promoting activity. We also demonstrated that stromal fibroblasts adjacent to epithelial cancer cells are senescent in human ovarian cancer specimens and in heterografts from RAS-transformed human ovarian epithelial cells and ovarian cancer cells. Moreover, Gro-1 was expressed at significantly higher amounts in ovarian cancer than in normal tissues and was higher in serum samples from women with ovarian cancer than in serum from women without ovarian cancer. These findings provide strong evidence that RAS-induced Gro-1 can reprogram the stromal microenvironment through the induction of senescence of fibroblasts and thus can promote tumorigenesis. Therefore, Gro-1 may be a therapeutic target as well as a diagnostic marker in ovarian cancer.
Dynamic Damping of Payload Motion for Cranes (1993)

The paper describes a novel strategy for damping of payload motion for various kinds of cranes used in construction, i.e., mobile cranes, boom or tower cranes and so forth, which can be implemented on existing equipment. Most research in this area concentrates on controlling the velocity and accelerations to eliminate inertial forces. However, it is almost impossible to realistically model the effects of wind, slippage of tires, or settlement of supports, etc. The research proposes an approach to control the swaying of the payload, regardless of the cause. The control strategy is based on applying periodic balancing forces and moments to the cable to damp out oscillations as and when detected. A feedback control system applied to the cable has the potential of providing an inexpensive and easily implemented solution. This is achieved by decoupling the payload and cable system from the structural members of the crane during the development of the control strategy. Effective control of the payload will improve safety, productivity and timeliness for a number of material handling operations.
Current progress, challenges and future prospects of diagnostic and therapeutic interventions in Alzheimer's disease (2018)

Alzheimer's disease (AD) is the most prevalent, progressive and multifaceted neurodegenerative disorder associated with cognition, memory and behavioural impairments. There is no approved diagnosis or cure for AD, and it affects both developed and developing countries and causes a significant social and economic burden. Extracellular senile plaques of amyloid beta (Aβ) and intracellular neurofibrillary tangles of phosphorylated Tau (pTau) in the brain are considered to be the pathophysiological hallmarks of AD. In an attempt to explain the complexity and multifactorial nature of AD, various hypotheses (Aβ aggregation, Tau aggregation, metal dyshomeostasis, oxidative stress, cholinergic dysfunction, inflammation and downregulation of autophagy) based on pathophysiological changes that occur during the onset and progression of AD have been proposed. However, none of the hypotheses is capable of independently explaining the pathological conditions observed in AD. The complex and multifaceted pathophysiological nature of AD has hampered the identification and validation of effective biomarkers for early diagnosis and the development of disease-modifying therapies. Nevertheless, the amyloid hypothesis is the most widely accepted and is closely correlated with disease symptoms of AD that encompass all the disease hypotheses. Therefore, amyloid plaques are ideal biomarkers for the development of an early diagnosis of AD. Similarly, the formation of amyloid plaques can also serve as a target for the design of therapeutic tools <i>via</i> an inclusive approach that considers multiple disease pathways involved in AD. Our review article briefly introduces pathophysiological factors involved in AD using interdependent but diverse hypotheses. Recent advances in the development of effective molecular tools and techniques for diagnostic and therapeutic interventions in AD, especially those in the advanced stages (clinical trials) of development, are given special consideration. In addition, contributions from our laboratory to the development of selective molecular tools for diagnostic and therapeutic interventions that target multifaceted toxicity in AD are also covered. In summary, we discuss diverse aspects of molecular mechanisms that underlie the pathogenesis of multifactorial AD, current progress and possible bottlenecks that have hampered the development of early diagnostic tools and effective drugs. Challenges and future prospects include the integration of various disease pathways for the successful development of an early diagnosis and effective drugs for the treatment of AD.
Comparing resting state fMRI de-noising approaches using multi- and single-echo acquisitions (2017)

Artifact removal in resting state fMRI (rfMRI) data remains a serious challenge, with even subtle head motion undermining reliability and reproducibility. Here we compared some of the most popular single-echo de-noising methods-regression of Motion parameters, White matter and Cerebrospinal fluid signals (MWC method), FMRIB's ICA-based X-noiseifier (FIX) and ICA-based Automatic Removal Of Motion Artifacts (ICA-AROMA)-with a multi-echo approach (ME-ICA) that exploits the linear dependency of BOLD on the echo time. Data were acquired using a clinical scanner and included 30 young, healthy participants (minimal head motion) and 30 Attention Deficit Hyperactivity Disorder patients (greater head motion). De-noising effectiveness was assessed in terms of data quality after each cleanup procedure, ability to uncouple BOLD signal and motion and preservation of default mode network (DMN) functional connectivity. Most cleaning methods showed a positive impact on data quality. However, based on the investigated metrics, ME-ICA was the most robust. It minimized the impact of motion on FC even for high motion participants and preserved DMN functional connectivity structure. The high-quality results obtained using ME-ICA suggest that using a multi-echo EPI sequence, reliable rfMRI data can be obtained in a clinical setting.
Studies on Synthesis of Antibacterial Agent (NM441). I. Kinetics and Mechanism of the Reaction of 4-(Bromomethyl)-5-methyl-1,3-dioxol-2-one with 1-Substituted Piperazine (NM394) (1994)

Abstract When a tertiary amine (4,NM441) is synthesized from 4-bromomethyl-5-methyl-1,3-dioxol-2-one (DMDO-Br) and a secondary amine (3,NM394) in N,N-dimethylformamide (DMF), the quaternary ammonium salt 5, the ring-opened compound 6, and the 1,2-adduct 7 are formed as by-products. The tertiary amine 4 is formed by nucleophilic attack of 3 on the α-carbon to the bromine atom of DMDO-Br. The ring-opened compound 6 is formed by nucleophilic attack of 3 on carbonyl carbon of DMDO-Br. The quaternary ammonium salt 5 is formed by the reaction of DMDO-Br with 4 (the Menshutkin reaction). Main pathway for the formation of 7 is the Michael addition of 3 to 6. Kinetics of the reactions have been studied and the methods to obtain 4 suppressing the formations of 5, 6, and 7 have been proposed based on the kinetic results.
Selectively <sup>2</sup>H‐labeledGlu/Asp: application to pK<sub>a</sub> measurements in Aβ amyloid peptides (2000)

Human Abeta peptides have been linked to Alzheimer's disease, and it is hypothesized that formation of amyloid as well as neurotoxicity are important events in the etiology of the disease. Previous studies have shown that the soluble precursor to Alzheimer's amyloid undergoes a pH-dependent folding transition as the self-assembly activity appears, and based upon inter-residue proximities, it was suspected that stabilization of the soluble form might rely upon formation of an intramolecular salt-bridge. However, pKa studies on a model 17-residue Abeta fragment supported an electrostatic model where a solvation imperative for charged side-chain atoms drives the folding process. To explore this model in an active 26-residue fragment as well as the full-length 40-residue Abeta peptide, pKa measurements were performed via 1H and 2H NMR. To overcome issues related to sensitivity and spin system degeneracy, specifically deuterated allyl protected-Fmoc amino acids were synthesized for incorporation into a series of peptides, and a high sensitivity 2H observe NMR probe was constructed.
Talking to the Community: client-service dialogue in rural health centres (2008)

Aims and RationaleThe principle of community participation in health services is well established. In practice, it has proven difficult to move much beyond limited involvement by a select group of community members. Difficulties appear to lie on both sides; professional resistance and community disengagement. This paper reports on some measures of community and professional attitudes to community participation undertaken as part of a project to test an innovative approach to fostering community-service dialogue.ApproachesQuestionnaires were administered to a purposive sample of 142 community members and 109 staff across two regional health centres exploring their experience with, and attitudes to, community-service dialogue. FindingsThe findings highlight some of the barriers to establishing a truly open dialogue between services and their communities. These include community members who dont report concerns and the perception, and to some extent the reality, that often these concerns are not passed on, valued and/or attended to by the service . While the majority of individual staff - but by no means all - support the need for, and say they value community input, a substantial percentage feel that their own services need to do more, not only to engage with client feedback but to attend to the voices of their own staff.Benefits to the CommunityAs rural and regional communities struggle to make the most of scarce health service resources it is vital that we find ways to overcome the barriers to allowing all voices to be heard and valued.
Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans (2007)

Prostaglandin D(2) (PGD(2)) is a cyclooxygenase (COX) product of arachidonic acid that activates D prostanoid receptors to modulate vascular, platelet, and leukocyte function in vitro. However, little is known about its enzymatic origin or its formation in vivo in cardiovascular or inflammatory disease. 11,15-dioxo-9alpha-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor PGDM) was identified by mass spectrometry as a metabolite of infused PGD(2) that is detectable in mouse and human urine. Using liquid chromatography-tandem mass spectrometry, tetranor PGDM was much more abundant than the PGD(2) metabolites, 11beta-PGF(2alpha) and 2,3-dinor-11beta-PGF(2alpha), in human urine and was the only endogenous metabolite detectable in mouse urine. Infusion of PGD(2) dose dependently increased urinary tetranor PGDM > 2,3-dinor-11beta-PGF(2alpha) > 11beta-PGF(2alpha) in mice. Deletion of either lipocalin-type or hemopoietic PGD synthase enzymes decreased urinary tetranor PGDM. Deletion or knockdown of COX-1, but not deletion of COX-2, decreased urinary tetranor PGDM in mice. Correspondingly, both PGDM and 2,3-dinor-11beta-PGF(2alpha) were suppressed by inhibition of COX-1 and COX-2, but not by selective inhibition of COX-2 in humans. PGD(2) has been implicated in both the development and resolution of inflammation. Administration of bacterial lipopolysaccharide coordinately elevated tetranor PGDM and 2,3-dinor-11beta-PGF(2alpha) in volunteers, coincident with a pyrexial and systemic inflammatory response, but both metabolites fell during the resolution phase. Niacin increased tetranor PGDM and 2,3-dinor-11beta-PGF(2alpha) in humans coincident with facial flushing. Tetranor PGDM is an abundant metabolite in urine that reflects modulated biosynthesis of PGD(2) in humans and mice.
Meshless least-squares method for solving the steady-state heat conduction equation (2005)

The meshless weighted least-squares (MWLS) method is a pure mesh less method that combines the moving least-squares approximation scheme and least-square discretization. Previous studies of the MWLS method for elastostatics and wave propagation problems have shown that the MWLS method possesses several advantages, such as high accuracy, high convergence rate, good stability, and high computational efficiency. In this paper, the MWLS method is extended to heat conduction problems. The MWLS computational parameters are chosen based on a thorough numerical study of 1-dimensional problems. Several 2-dimensional examples show that the MWLS method is much faster than the element free Galerkin method (EFGM), while the accuracy of the MWLS method is close to, or even better than the EFGM. These numerical results demonstrate that the MWLS method has good potential for numerical analyses of heat transfer problems.
A Validated Risk Score for In-Hospital Mortality in Patients With Heart Failure From the American Heart Association Get With the Guidelines Program (2009)

The GWTG-HF risk score uses commonly available clinical variables to predict in-hospital mortality and provides clinicians with a validated tool for risk stratification that is applicable to a broad spectrum of patients with heart failure, including those with preserved left ventricular systolic function.
Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon, and melphalan (1994)

The preliminary, impressive results reported in other series were not completely confirmed in this study adopting the same treatment scheme. Further clinical experience and biologic data are needed to state the real efficacy of the approach and to reduce the severe general toxicity consistently associated with this type of treatment.
Modeling and analysis of computer system availability (1987)

The quantitative evaluation of computer-system availability is becoming increasingly important in the design and configuration of commercial computer systems. This paper deals with methods for constructing and solving large Markov-chain models of computer-system availability. A set of powerful high-level modeling constructs is discussed that can be used to represent the failure and repair behavior of the components that comprise a system, including important component interactions, and the repair actions that are taken when components fail. If time-independent failure and repair rates are assumed, then a time-homogeneous continuous-time Markov chain can be constructed automatically from the modeling constructs used to describe the system. Markov chains having tens of thousands of states can be readily constructed in this manner. Therefore, techniques that are particularly suitable for numerically solving such large Markov chains are also discussed, including techniques for computing the sensitivities of availability measures with respect to model parameters. A computer system modeling example is presented to illustrate the use of these modeling and analysis techniques. The modeling constructs, automatic Markov-chain construction, and model-solution methods have been implemented in a program package called the System Availability Estimator (SAVE).
Implantable endoscopic gastric bypass – device and experimental procedure (2009)

Malabsorptive bariatric surgery is an effective treatment option for morbid obesity, but may be associated with complications and side effects. We have developed a new experimental approach to creating a gastric bypass through an intraluminal access. The goal is to reduce postoperative complications and to reduce mid-term side-effects of malabsorptive bypass food passage and to allow easy reversion of the procedure. The new procedure is based on an implantable gastric bypass device, installed by combined transoral flexible and minimally invasive abdominal access. The newly developed device and procedure were studied in a pilot experimental trial in the porcine animal model (n=8). Endpoints were the feasibility of the technical procedure, the ability of the animal to eat and digest food, the implant functionality over the survival period and the absence of major complications over a short-term follow-up (one week). The procedure was technically successful in all eight animals. Animals were able to take in food and water till sacrifice. Four animals had major complications (one abdominal wall dehiscence, one invagination ileus of the small bowel, one dehiscence of the gastro-jejunal anastomosis and one myocardial infarction) and did not complete follow-up. In two cases migration of the device into the stomach was observed. The difference between our experimental technique and the gold standard surgical methods for gastric bypass consists of the endoluminal approach by implanting an intraluminal gastric bypass device. This concept avoids gastric transsection and an additional anastomosis and enables an adjustable food passage between the bypass and the natural duodenal passage. Further long-term follow-up studies are required.