gebhart/patrepeval huggingface dataset:
Additional binding mechanism of palonosetron to the 5-HT3 receptor versus first generation 5-HT3 receptor antagonists (2007)

19583 Background: Palonosetron has a higher binding affinity and longer plasma half-life than first generation 5-HT 3 receptor antagonists. Clinical trials have demonstrated that a single intravenous dose of palonosetron 0.25 mg provides better protection from chemotherapy-induced nausea and vomiting than other 5-HT 3 receptor antagonists throughout the 5-day post-chemotherapy period. The purpose of this work is to determine differences in the molecular interactions of the antagonists with the receptor that could help explain the clinical efficacy differences. Methods: Molecular ligand-receptor relationships for commonly used 5-HT 3 receptor antagonists were investigated. In particular, competitive vs. potential allosteric interactions between ondansetron, granisetron and palonosetron and the 5-HT 3 receptor were examined. Binding experiments were carried out using each unlabeled antagonist in competition with [ 3 H]-antagonist. Concentrations of [ 3 H]-antagonists used in these experiments included the equilibrium dissociation constant (K i ) and several-fold K i values in an effort to represent the probable concentrations of each antagonist at the receptor site in vivo. The inhibitory concentration of unlabeled antagonist needed to observe half maximal binding (IC 50 ) as a function of [ 3 H]-antagonist concentration was plotted for comparisons between ondansetron, granisetron and palonosetron. Results: A plot of the concentration of unlabeled antagonist needed to observe IC 50 as a function of [ 3 H]- antagonist concentration was linear when ondansetron and granisetron were in competition. On the other hand, when palonosetron was in competition with either granisetron or ondansetron the plot was curvilinear in each case. Conclusions: These results indicate that palonosetron exhibits both competitive and allosteric interactions with the 5-HT 3 receptor, in contrast to ondansetron and granisetron which display strictly competitive antagonism. As allosteric interactions may induce changes in the receptor conformation, we can speculate that palonosetron's dual action on the 5-HT 3 -receptor could induce amplification of its inhibitory effect at the primary receptor binding site. No significant financial relationships to disclose.
Timely Report Delivery in Social Swarming Applications (2012)

In social swarming applications, participants equipped with 3G and WiFi-capable smart phones are tasked to provide reports (possibly voluminous ones that include full-motion video) about their immediate environment to a central coordinator. In this paper, we consider the problem of timely delivery of these reports: each report has an associated deadline and the goal of the system is to retrieve as many reports as possible (or retrieve the most valuable reports), while satisfying each report's deadline. Reporters can use their cellular interface to upload their reports, but can also ask neighbors (using their faster WiFi interface) to help upload parts of their reports. Under an assumption that WiFi transmission delays are negligible, we first show that there exists a polynomial time optimal solution using an earliest-deadline-first (EDF) strategy for achieving the goals described above. In practice, WiFi delays are not negligible: in this case, it turns out that the scheduling problem is strongly NP-hard. We formulate two heuristic algorithms, and show, through simulations with real-world measurements, that these heuristics perform 2-4× better than without peer-assistance, and within 60% of an upper-bound on the optimal.
Excitation Wavelength Dependence of Terahertz Emission from Indium Nitride Multiple Quantum Wells (2007)

We report the excitation wavelength dependence of terahertz emission from N-face InN/InGaN multiple quantum wells relative to that from bulk N-face InN when excited by femtosecond optical pulses tunable from 800 nm to 1700 nm.
<title>Automated scenario generation</title> (2003)

This paper will discuss automated scenario generation (Sgen) techniques to support the development of simulation scenarios. Current techniques for scenario generation are extremely labor intensive, often requiring manual adjustments to data from numerous sources to support increasingly complex simulations. Due to time constraints this process often prevents the simulation of a large numbers of data sets and the preferred level of “what if analysis”. The simulation demands of future mission planning approaches, like Effects Based Operations (EBO), require the rapid development of simulation inputs and multiple simulation runs for those approaches to be effective. This paper will discuss an innovative approach to the automated creation of complete scenarios for mission planning simulation. We will discuss the results of our successful Phase I SBIR effort that validated our approach to scenario generation and refined how scenario generation technology can be directly applied to the types of problems facing EBO and mission planning. The current stovepipe architecture marries a scenario creation capability with each of the simulation tools. The EBO-Scenario generation toolset breaks that connection through an approach centered on a robust data model and the ability to tie mission-planning tools and data resources directly to an open Course Of Action (COA) analysis framework supporting a number of simulation tools. In this approach data sources are accessed through XML tools, proprietary DB structures or legacy tools using SQL and stored as an instance of Sgen Meta Data. The Sgen Meta Data can be mapped to a wide range of simulation tools using a Meta Data to simulation tools mapping editor that generates an XSLT template describing the required data translation. Once the mapping is created, Sgen will automatically convert the Meta Data instance, using XSLT, to the formats required by specific simulation tools. The research results presented in this paper will show how the complex demands of mission planning can be met with current simulation tools and technology.
T-ray detection in 0.35-μm CMOS technology (2014)

Interest in array based imaging of terahertz energy (T-Rays) has gained traction lately, specifically using a CMOS process due to its ease of manufacturability and the use of MOSFETs as a detection mechanism. Incident terahertz radiation on to the gate channel region of a MOSFET can be related to plasmonic response waves which change the electron density and potential across the channel. The 0.35 &mu;m silicon CMOS MOSFETs tested in this work contain varying structures, providing a range of detectors to analyze. Included are individual test transistors for which various operating parameters and modes are studied and results presented. A focus on single transistor-antenna testing provides a path for discovering the most efficient combination for coupling 0.2 THz band energy. An evaluation of fabricated terahertz band test detection MOSFETs is conducted. Sensitivity analysis and responsivity are described, in parallel with theoretical expectations of the plasmonic response in room temperature conditions. A maximum responsivity of 40 000 V/W and corresponding NEP of 10 pW/Hz<sup>1/2</sup> (&plusmn;10% uncertainty) is achieved.
Sulfide catabolism ameliorates hypoxic brain injury (2021)

The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain's sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.
Synthesis of ZnO Thin Films by Metal-Organic CVD of Zn(CH3COO)2 (1998)

Zinc oxide films were deposited by CVD in air and nitrogen under atmospheric conditions using zinc acetate and zinc oxyacetate as the precursors. Factors for obtaining reproducible depositions were identified. The activation energies using zinc acetate as the precursor were ∼ 45 kJ mol–1 (±20%) both in air and in nitrogen, and ∼ 45 kJ mol–1 (±20%) in air, using zinc oxyacetate as the precursor. The concentration dependence of the deposition rate was ≤ 1/3. Crystalline films with lower carbon content were deposited at lower substrate temperatures under atmospheric conditions than at reduced pressures. Water enhanced the (002) orientation of the films and increased the deposition rate only in nitrogen (not in air). Overall, this study provides the first quantitative information about the kinetics of the deposition of ZnO from zinc acetate and zinc oxyacetate.
Postprandial symptoms in patients with symptoms of gastroparesis: roles of gastric emptying and accommodation (2022)

Patients with delayed and normal gastric emptying (GE) had similar symptom profiles during gastric emptying scintigraphy (GES). Idiopathic patients with symptoms of gastroparesis had less gastric retention by GES; but more symptoms after GES meal and after water load satiety test (WLST) compared with diabetic patients. In patients with symptoms of gastroparesis, symptoms after WLST increased with decreasing water consumption. Early satiety and loss of appetite were associated with decreased water consumption during WLST. Thus, impaired accommodation and perhaps visceral hypersensitivity are important in explaining postprandial symptoms in gastroparesis.
LITESPARK-022: A phase 3 study of pembrolizumab + belzutifan as adjuvant treatment of clear cell renal cell carcinoma (ccRCC). (2022)

TPS4602 Background: Patients with locally advanced renal cell carcinoma (RCC) may experience recurrence after surgery. In the phase 3 KEYNOTE-564 (NCT03142334) trial, adjuvant pembrolizumab demonstrated significant improvement in disease-free survival (DFS) in ccRCC, leading to FDA approval of pembrolizumab (November 17, 2021) for adjuvant treatment of patients with RCC at intermediate-high or high risk for recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. Despite benefit of pembrolizumab, there is an unmet need for more effective adjuvant treatment for patients at risk for recurrence after definitive surgery. The HIF-2α inhibitor belzutifan (MK-6482) has shown activity and good tolerability in patients with advanced ccRCC and von Hippel-Lindau (VHL) disease–associated RCC. Combining belzutifan with pembrolizumab may be a therapeutic option as adjuvant treatment of ccRCC. This global, multicenter, double-blind, randomized, phase 3 study LITESPARK-022 (NCT05239728) is designed to compare the efficacy and safety of belzutifan + pembrolizumab with that of placebo + pembrolizumab as adjuvant treatment of ccRCC after nephrectomy. Methods: Approximately 1600 patients with histologically or cytologically confirmed RCC (intermediate-high [pT2, grade 4 or sarcomatoid, N0, M0 or pT3, any grade, N0, M0], high [pT4, any grade, N0, M0 or pT, any stage/grade, N+, M0] or M1 NED [patients who present with the primary kidney tumor and solid, isolated, soft tissue metastases that can be resected at the time of nephrectomy or ≤2 years from nephrectomy) with a clear cell component and had not previously received systemic therapy will be enrolled. Patients must have undergone nephrectomy and/or metastasectomy ≤12 weeks before randomization and be tumor free, confirmed by CT/MRI. Stratification factors are tumor grade (1 or 2 vs 3 or 4) and risk type (intermediate-high vs high vs M1 NED). Patients will be randomly assigned 1:1 to receive belzutifan 120 mg orally once daily + pembrolizumab 400 mg IV every 6 weeks (Q6W) or oral placebo + pembrolizumab 400 mg IV Q6W. Pembrolizumab treatment will be administered for up to 9 doses (̃1 year); belzutifan and placebo may be continued for a maximum of 54 weeks. Disease recurrence will be evaluated radiologically Q12W from randomization through year 2, Q16W in years 3-5, and Q24W in years 6 and beyond. Adverse events (AEs) will be monitored by NCI CTCAE v5.0 through 30 days (90 days for serious AEs) after cessation of study drug. The primary end point is DFS, as assessed by investigator, defined as time from randomization to first documented event of local recurrence, occurrence of distant kidney cancer metastasis, or death from any cause, whichever occurs first. The key secondary end point is overall survival. Other secondary end points are safety, disease recurrence–specific survival and patient-reported outcomes. Clinical trial information: NCT05239728.
Host‐Pathogen Interactions: The Attributes of Virulence (2001)

Virulence is one of a number of possible outcomes of host-microbe interaction. As such, microbial virulence is dependent on host factors, as exemplified by the pathogenicity of avirulent microbes in immunocompromised hosts and the lack of pathogenicity of virulent pathogens in immune hosts. Pathogen-centered views of virulence assert that pathogens are distinguished from nonpathogens by their expression of virulence factors. Although this concept appears to apply to certain microbes that cause disease in normal hosts, it does not apply to most microbes that cause disease primarily in immunocompromised hosts. The study of virulence is fraught with the paradox that virulence, despite being a microbial characteristic, can only be expressed in a susceptible host. Thus, the question "What is a pathogen?" begs the question, "What is the outcome of the host-microbe interaction?" We propose that host damage provides a common denominator that translates into the different outcomes of host-microbe interaction.
Human T Cell Leukemia Virus Envelope Binding and Virus Entry Are Mediated by Distinct Domains of the Glucose Transporter GLUT1 (2005)

The glucose transporter GLUT1, a member of the multimembrane-spanning facilitative nutrient transporter family, serves as a receptor for human T cell leukemia virus (HTLV) infection. Here, we show that the 7 amino acids of the extracellular loop 6 of GLUT1 (ECL6) placed in the context of the related GLUT3 transporter were sufficient for HTLV envelope binding. Glutamate residue 426 in ECL6 was identified as critical for binding. However, binding to ECL6 was not sufficient for HTLV envelope-driven infection. Infection required two additional determinants located in ECL1 and ECL5, which otherwise did not influence HTLV envelope binding. Moreover the single N-glycosylation chain located in ECL1 was not required for HTLV infection. Therefore, binding involves a discrete determinant in the carboxyl terminal ECL6, whereas post-binding events engage extracellular sequences in the amino and carboxyl terminus of GLUT1.
The influence of load knowledge on lifting technique (1993)

The purpose of this study was to analyse the influence of load knowledge on lifting technique. Ten men lifted a box containing either no weight or weights of 150, 250 or 300 N with and without knowledge of what was inside the box. The kinetics and kinematics of the lift were analysed using a force plate, an optoelectronic motion analysis system, and a rigid body link model. At 0 N lifting, the unknown load resulted in a jerk-like motion and a significantly increased peak L5-S1 flexion-extension moment. At 150 N there was also a significant increase in the speed of trunk extension with unknown weights, but the L5-S1 moment remained unchanged. At higher load levels there were only minor differences between lifting techniques when knowing and not knowing the load. We conclude that lifts are approached assuming a certain weight, and that when the assumption is wrong and the load lighter than anticipated lifting is performed with a 'jerking' motion, creating unnecessary loads on the lower back.
CMOS compatible 250 V lateral insulated base transistors (2002)

The performance of various insulated base transistors implemented with a digital CMOS compatible high-voltage integrated circuit process was demonstrated. Design modifications in the lateral insulated base transistor (LIBT) structures have been proposed, and the performance of the improved LIBTs has been compared with that of a conventional LIBT structure. These modifications are based on the effective use of charge-controlled n/sup +/ buried layers to improve the on-state capability of the device. Four different types of LIBT structures have been fabricated and tested. The experimental analysis of the CMOS-compatible LIBTs discussed shows that the n/sup +/ buried layer placed under the p well plays a crucial role in improving the device performance. The improved LIBT structure with n/sup +/ buried layers incorporated near the collector and the p well regions shows the best characteristics with high voltage blocking capability, low specific on-resistance, and a low turn-off delay. A specific on-resistance of 0.016 Omega -cm/sup 2/ and a turn-off delay of 90 ns were obtained in the improved LIBT structure, which can withstand up to 250 V.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Topological quantum phase transition in magnetic topological insulator upon magnetization rotation (2018)

We report a continuous phase transition between quantum-anomalous-Hall and trivial-insulator phases in a magnetic topological insulator upon magnetization rotation. The Hall conductivity transits from one plateau of quantized Hall conductivity ${e}^{2}/h$ to the other plateau of zero Hall conductivity. The transition curves taken at various temperatures cross almost at a single point, exemplifying the critical behavior of the transition. The slope of the transition curves follows a power-law temperature dependence with a critical exponent of $0.61$. This suggests a common underlying origin in the plateau transitions between the quantum anomalous Hall and quantum Hall systems, which is a percolation of one-dimensional chiral edge channels.
Antiepileptic Drugs Modulate Alzheimer-Related Tau Aggregation in a Neuronal Activity-Independent Manner (2023)

Antiepileptic drugs may modify the tau pathology in AD in a neural activity-independent manner. Our finding may provide an important insight into the optimization of antiepileptic drug therapy in older adults with dementia.
Fabrication of Diffractive Optics for Dense Optical Interconnects in Optical Computing. (2016)

Abstract not provided.
Exploring the impact of advanced front-end processing on NIST speaker recognition microphone tasks. (2012)

The NIST speaker recognition evaluation (SRE) featured mi-crophone data in the 2005-2010 evaluations. The preprocess-ing and use of this data has typically been performed with tele-phone bandwidth and quantization. Although this approach is viable, it ignores the richer properties of the microphone data— multiple channels, high-rate sampling, linear encoding, ambient noise properties, etc. In this paper, we explore alternate choices of preprocessing and examine their effects on speaker recogni-tion performance. Specifically, we consider the effects of quan-tization, sampling rate, enhancment, and two-channel speech activity detection. Experiments on the NIST 2010 SRE inter-view microphone corpus demonstrate that performance can be dramatically improved with a different preprocessing chain. 1.
International Workshop on Human-In-the-Loop Data Analytics (HILDA) (2019)

The Human In the Loop Data Analytics (HILDA) workshop aims to foster interdisciplinary efforts that tackle important challenges in better supporting humans in the loop in the context of data-intensive computations, such as interactive data exploration, integration, analytics, and machine learning. Over the past several years, HILDA has brought together DB researchers interested in the distinctive ways that people impact data management tasks, as well as like-minded researchers in other communities, such as Information Visualization, Data Mining/Machine Learning, and HCI. The work presented at HILDA covers a broad range of topics, from algorithmic, interface, and system design to the user's cognitive, physical, and goal-seeking perspectives when managing and exploring data as well as notions of approximation/prediction. This year, we continued to encourage submissions for initial ideas and visions, early reports of work in progress, as well as reflections on completed projects.
Validity of the Cold Pressor Test and Pain Sensitivity Questionnaire via online self-administration (2019)

Abstract To determine the feasibility of complex home-based phenotyping, 1,876 research participants from the customer base of 23andMe participated in an online version of a Pain Sensitivity Questionnaire (PSQ) as well as a cold pressor test (CPT) which is used in clinical assessments of pain. Overall our online version of the PSQ performed similarly to the original pen-and-paper version. Construct validity of the PSQ total was demonstrated by internal consistency and consistent discrimination between more and less painful items. Criterion validity was demonstrated by correlation with pain sensitivity as measured by the cold pressor test. Within the same cohort we performed a cold pressor test using a layperson description and household equipment. Comparison with published reports from controlled studies revealed similar distributions of cold pain tolerance times (i.e., time elapsed before removing the hand from the water). Of those who elected to participate in the CPT, a large majority of participants did not report issues with the test procedure or noncompliance to the instructions (97%). We confirmed a large sex difference in CPT thresholds in line with published data, such that women removed their hands from the water at a median of 54.2 seconds, with men lasting for a median time of 82.7 seconds (Kruskal-Wallis statistic, p &lt; 0.0001), but other factors like age or current pain treatment were at most weakly associated, and inconsistently between men and women. We introduce a new paradigm for performing pain testing, called testing@home, that, in the case of cold nociception, showed comparable results to studies conducted under controlled conditions and supervision of a health care professional. Summary Research paradigms employing home-based phenotyping are feasible, with both questionnaires and self-administration of a well-established experimental human pain model yielding similar results compared to controlled settings.
The absolute configurations of the methionine sulphoximines (1969)

B. W. Christensen, A. Kjær, S. Neidle and D. Rogers, J. Chem. Soc. D, 1969, 169 DOI: 10.1039/C29690000169
Interactions between environmental sensitivity and gut microbiota are associated with biomarkers of stress-related psychiatric symptoms (2023)

Our study indicates that high environmental sensitivity can be a risk factor for inflammation and gut permeability, when the gut microbiota diversity is low, suggesting a brain-gut-microbiota axis interaction.
ChemInform Abstract: Chiral Lactones by Asymmetric Hydrogenation — A Step Forward in (+)‐Biotin Production (2011)

Abstract Review: 32 refs.