gebhart/patrepeval huggingface dataset:
mRNA COVID-19 vaccine effectiveness against SARS-CoV-2 infection in a prospective community cohort, rural Wisconsin, November 2020-December 2021 (2021)

Abstract Reduced COVID-19 vaccine effectiveness (VE) has been observed with increasing predominance of the Delta variant. In a prospective rural community cohort of 1265 participants, VE against symptomatic and asymptomatic SARS-CoV-2 infection was 56% for mRNA COVID-19 vaccines.
Ubiquitin specific protease-13 independently regulates parkin ubiquitination and alpha-synuclein clearance in alpha-synucleinopathies (2018)

Ubiquitin specific proteases (USPs) are de-ubiquitinases (DUBs) that control protein ubiquitination cycle. The role of DUBs is poorly understood in neurodegenerative diseases. We found that USP13 is overexpressed in post-mortem Parkinson's disease (PD) brains. We investigated whether changes in USP13 levels can affect two molecules, parkin and alpha-synuclein, that are implicated in PD pathogenesis. Parkin is an E3 ubiquitin ligase that is regulated by ubiquitination and targets certain proteins for degradation, and alpha-synuclein may be ubiquitinated and recycled in the normal brain. We found that USP13 independently regulates parkin and alpha-synuclein ubiquitination in models of alpha-synucleinopathies. USP13 shRNA knockdown increases alpha-synuclein ubiquitination and clearance, in a parkin-independent manner. Furthermore, USP13 overexpression counteracts the effects of a tyrosine kinase inhibitor, Nilotinib, while USP13 knockdown facilitates Nilotinib effects on alpha-synculein clearance, suggesting that alpha-synuclein ubiquitnation is important for its clearance. These studies provide novel evidence of USP13 effects on parkin and alpha-synuclein metabolism and suggest that USP13 is a potential therapeutic target in the alpha-synucleinopathies.
Complexity of Advanced Glycation End Products in Foods: Where Are We Now? (2018)

Recent clinical trials indicate that consumption of dietary advanced glycation end products (AGEs) may promote the development of major chronic diseases. However, the outcomes of human studies have proven inconclusive as a result of estimates of the total AGE intake being taken with a single AGE in most of the studies. In this perspective, we summarized the major types of AGEs derived from proteins, nucleic acids, and phospholipids during food processing and suggested a panel of AGEs as markers to better measure the intake of total dietary AGEs in human studies.
Search for new superconductors in the Y-Ni-B-C system (1997)

We have searched for superconductivity in a wide variety of stoichiometries in the Y-Ni-B-C system, using Yx(NiB)Cy phase spread alloy thin films and the magnetic field modulated microwave absorption technique. The superconducting critical temperature (Tc) varies with the stoichiometry, showing the highest Tc for a Y/Ni ratio of 1/2, attributed to the YNi2B2C phase. We found no other superconducting phases with a Tc higher than 10 K. Furthermore, a search in YxNiB(C1−zNz)y and YxNiBNy phase spread alloys showed no superconductivity.
Heart–kidney crosstalk and role of humoral signaling in critical illness (2014)

Organ failure in the heart or kidney can initiate various complex metabolic, cell-mediated and humoral pathways affecting distant organs, contributing to the high therapeutic costs and significantly higher morbidity and mortality. The universal outreach of cells in an injured state has myriad consequences to distant organ cells and their milieu. Heart performance and kidney function are closely interconnected and communication between these organs occurs through a variety of bidirectional pathways. The term cardiorenal syndrome (CRS) is often used to describe this condition and represents an important model for exploring the pathophysiology of cardiac and renal dysfunction. Clinical evidence suggests that tissue injury in both acute kidney injury and heart failure has immune-mediated inflammatory consequences that can initiate remote organ dysfunction. Acute cardiorenal syndrome (CRS type 1) and acute renocardiac syndrome (CRS type 3) are particularly relevant in high-acuity medical units. This review briefly summarizes relevant research and focuses on the role of signaling in heart-kidney crosstalk in the critical care setting.
A Phase 2, Randomized, Active-controlled, Observer-blinded Study to Assess the Immunogenicity, Tolerability and Safety of Bivalent rLP2086, a Meningococcal Serogroup B Vaccine, Coadministered With Tetanus, Diphtheria and Acellular Pertussis Vaccine and Serogroup A, C, Y and W-135 Meningococcal Conjugate Vaccine in Healthy US Adolescents (2016)

Bivalent rLP2086 given concomitantly with MCV4 + Tdap met all noninferiority immunogenicity criteria without a clinically meaningful increase in reactogenicity. MCV4 and bivalent rLP2086 coadministration would provide coverage against the 5 major disease-causing serogroups.
Discovery and Characterization of (R)-6-Neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894), an Alkyne-Lacking Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator Profiled in both Rat and Nonhuman Primates (2017)

We previously observed a cutaneous type IV immune response in nonhuman primates (NHP) with the mGlu<sub>5</sub> negative allosteric modulator (NAM) 7. To determine if this adverse event was chemotype- or mechanism-based, we evaluated a distinct series of mGlu<sub>5</sub> NAMs. Increasing the sp<sup>3</sup> character of high-throughput screening hit 40 afforded a novel morpholinopyrimidone mGlu<sub>5</sub> NAM series. Its prototype, (R)-6-neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894, 8), possessed favorable properties and a predicted low clinical dose (2 mg twice daily). Compound 8 did not show any evidence of immune activation in a mouse drug allergy model. Additionally, plasma samples from toxicology studies confirmed that 8 did not form any reactive metabolites. However, 8 caused the identical microscopic skin lesions in NHPs found with 7, albeit with lower severity. Holistically, this work supports the hypothesis that this unique toxicity may be mechanism-based although additional work is required to confirm this and determine clinical relevance.
Excitation energies from time-dependent density functional theory using exact and approximate functionals (2000)

The role of the exchange-correlation potential and the exchange-correlation kernel in the calculation of excitation energues from time-dependent density functional theory is studied. Excitation energies of the He and Be atoms are calculated, both from the exact ground-state Kohn-Sham potential, and from two orbital-dependent approximations. These are exact exchange and self-interaction corrected local density approximation (SIC-LDA), both calculated using the Krieger-Li-Iafrate (KLI) approximation. For the exchange-correlation kernela, three adiabatic approximations were tested: The local density approximation, exact exchange, and SIC-LDA. The choice of the ground-state exchange-correlation potential has the largest impact on the absolute position of most excitation energies. In particular, orbital-dependent approximate potentials result in a uniform shift of the transition energies to the Rydberg states.
Size-Controlled Flow Synthesis of Gold Nanoparticles Using a Segmented Flow Microfluidic Platform (2012)

Segmented flow is often used in the synthesis of nanomaterials to achieve narrow particle size distribution. The narrowness of the distribution is commonly attributed to the reduced dispersion associated with segmented flows. On the basis of the analysis of flow fields and the resulting particle size distribution, we demonstrate that it is the slip velocity between the two fluids and internal mixing in the continuous-phase slugs that govern the nature of the particle size distribution. The reduction in the axial dispersion has less impact on particle growth and hence on the particle size distribution. Synthesis of gold nanoparticles from HAuCl(4) with rapid reduction by NaBH(4) serves as a model system. Rapid reduction yields gold nuclei, which grow by agglomeration, and it is controlled by the interaction of the nuclei with local flow. Thus, the difference in the physical properties of the two phases and the inlet flow rates ultimately control the particle growth. Hence, a careful choice of continuous and dispersed phases is necessary to control the nanoparticle size and size distribution.
Multi-stage object classification featuring confidence analysis of classifier and inclined local Naive Bayes nearest neighbor (2014)

We propose a two-stage classification framework for image recognition which conjunctively uses parametric and non-parametric approaches. In the first stage, input images are classified using a bag-of-features (BoF) based method with a multi-class classifier. The results are categorized into two groups by our confidence analysis: highly confident and less confident. The images with less confidence are re-classified in the second stage using our inclined local naive bayes nearest neighbor (IL-NBNN). In the original local NBNN, the similarity between the input image and its k-NN classes are calculated aiming at higher discriminability and computational efficiency. Our IL-NBNN virtually calculates the similarity between all the classes efficiently by incorporating the confidence order obtained in the first stage. As a result, efficient and accurate image classification has been achieved with very small extra cost. The experiments using the three image datasets show the validity of our proposed algorithm.
Identification of two enhancer elements downstream of the human c-mycgene (1995)

Expression of the proto-oncogene c-myc is tightly regulated in vivo. Transcription of c-myc is assumed to be controlled by a number of positive and negative cis-acting control elements located upstream or within exon 1 and intron 1. However, these regulatory elements are not sufficient for c-myc expression after stable transfection or in transgenic mice. Transcription of c-myc in vivo thus requires additional control elements located outside the tested HindIII-EcoRI gene fragment. In order to identify these putative additional control elements, we mapped DNase I hypersensitive sites around the human c-myc gene in nine different tumor cell lines and in primary lymphocytes. Within the coding and 5' region of the gene, an almost identical pattern of DNase I hypersensitive sites was detected in the various cells. In contrast, chromatin analysis of the c-myc 3' region revealed a complex pattern of constitutive and tissue-specific DNase I hypersensitive sites. In enhancer trap experiments we identified two cis-acting control elements, both co-localizing with DNase I hypersensitive sites, that stimulated c-myc transcription after transient transfection in Raji or HeLa cells. Both regulatory elements exerted their enhancer activity in either orientation and regardless of their location within the plasmids. Both elements also conferred activation on a heterologous promoter. The association of these enhancers with DNase I hypersensitive sites, indicating their functional activity in vivo, make them potential candidates for the postulated regulatory control element(s) required for c-myc expression in vivo.
bcl-2 Gene Therapy Exacerbates Excitotoxicity (1999)

The protooncogene bcl-2 can block neuronal death from both naturally occurring apoptosis and exogenous insults. bcl-2 is therefore a promising candidate for the prevention of excitotoxic neuronal death. Using an adeno-associated viral vector, we delivered the bcl-2 gene to the ganglion cell layer of the rat eye. We hypothesized that infection with bcl-2 would protect ganglion cells against excitotoxic cell death. However, retinal infection with bcl-2 increased ganglion cell susceptibility to both axonal injury and intravitreal NMDA. Our study--intended to explore the possibility of bcl-2 transduction as an in vivo therapeutic approach--revealed a deleterious effect of bcl-2 transduction.
Thermoeconomic Optimization of a Sensible-Heat Thermal-Energy-Storage System: A Complete Storage Cycle (1999)

An analytical model for the second-law-based thermoeconomic analysis and optimization of a sensible-heat-storage system is derived and discussed, in which the storage element is both heated and cooled by flowing streams of gases. In this analysis, monetary values are attached to the irreversible losses caused by the finite temperature difference heat transfer and pressure drop in the storage system. Important dimensionless parameters are identified and the results are presented in terms of the optimum dimensionless charging time θS,opt as a function of a dimensionless temperature difference τ, as well as the optimum number of heat transfer units NTUS,opt, as a function of the dimensionless unit cost per unit heat conductance γUA and τ of the storage systems. The systems analyzed are optimized by introducing a new performance criterion described as the cost rate number, Γ*. Several example problems are also presented and the results are compared with that obtained from Krane’s analysis to illustrate the usefulness of the present approach. The influence of important unit cost parameters on NTUS,opt and θS,opt, are also studied in somewhat more detail.
AFFORDING REALISTIC STOPPING BEHAVIOR: A CARDINAL CHALLENGE FOR DRIVING SIMULATORS (2001)

Drivers adopt nearly constant deceleration rates when intending to stop at a distant target. In driving simulators however we often observe different control strategies. Depending on simulator fidelity, deceleration profiles range from saw-tooths to multi-modal profiles to profiles that do resemble those seen in reality. These deviations from reality suggest that drivers have difficulty controlling their vehicle based on the assumption that a constant deceleration rate (approximately constant brake pedal depression) is most efficient at least from a control and attention point of view. The discrepancy between reality and simulation is attributed to the fact that perception of distance, speed, and acceleration, as well as time-to-collision are biased in all current driving simulators (i.e. they are perceived at scaled magnitudes). We introduce a driver model for stopping behavior and demonstrate its capability to reproduce the braking profiles observed in various driving simulators by varying only two model parameters: i) control gain, and ii) the perceived time-to-collision at which braking is initiated. For a given set of simulator dependent perceptual biases in distance, speed, and acceleration estimation, it appears that drivers only need to adapt these two parameters to achieve efficient deceleration, which in some cases takes surprisingly much practice. The reason is attributed to the fact that such a simple adaptation is perceived as counter intuitive when the perceptual biases do not satisfy a particular ratio. If for example, acceleration perception is accurate but speed and
Influence of synthetic jet location on boundary layer separation control (2004)

When synthetic jet actuators are used to control flow separation in practical situations, it is anticipated that the orifices will be distributed in the form of an array. Wind tunnel experiments were conducted to investigate the effect of the location and number of these actuators on boundary layer separation. Three synthetic jets were located upstream of the separation point in undisturbed flow, and the mean and root mean-square (RMS) velocity profiles were measured at several axial locations within the separated flow region. This paper reports the effect of actuator placement and the integrated effectiveness of two and three synthetic jets with different forcing voltages and frequencies.
Durability of response in ZUMA-1, the pivotal phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients (Pts) with refractory large B-cell lymphoma. (2018)

3003 Background: Axi-cel, an anti-CD19 CAR T cell therapy, demonstrated significant clinical benefit and a manageable safety profile for pts with refractory large B cell lymphoma in ZUMA-1 (Neelapu & Locke et al. NEJM. 2017). These results led to its approval by the US FDA for the treatment of adult pts with relapsed or refractory large B cell lymphoma after ≥ 2 prior lines of therapy. Here, we examined responses over time in phase 2 of ZUMA-1. Methods: Pts with refractory large B cell lymphoma received 2 × 106 CAR T cells/kg after low-dose conditioning (Neelapu & Locke et al. NEJM. 2017). Best objective response rates (BOR) were analyzed locally by investigators (local) and centrally by independent review committee (IRC; Cheson et al. J Clin Oncol. 2007); concordance was measured as the percentage of pts whose IRC matched local. Results: As of 8/11/17, median follow-up (f/u) was 15.1 mo for the 101 pts treated with axi-cel. While the BOR of 82% at primary analysis (PA; median f/u 8.7 mo) by local remained consistent (83%) at long-term f/u (LTFU; median of 15.1 mo), complete response (CR) rates increased from 54% to 58% (Table). Out of 34 pts with partial response (PR) at 1 mo, 11 (32%) converted to CR by the LTFU. High concordance (77% - 79%) was observed for objective response rates (ORR [CR + PR]) between local and IRC at all times assessed. Landmark analysis of progression-free survival (PFS) by response status (per local) revealed that most of the 60 pts with disease control (stable disease or better) at 3 mo had prolonged disease control with a 73% 12-mo PFS rate. Of the 42 pts with CR and 9 with PR at 3 mo, the 12-mo PFS rates were 79% and 78%, respectively. Conclusions: Treatment with axi-cel induces high response rates in pts with refractory large B cell lymphoma. CR rates increased through the LTFU, suggesting that responses deepen over time and that pts with PR can achieve CR as late as a year post-infusion. ORR at 3 mo may be prognostic for prolonged PFS. Drs Locke and Neelapu contributed equally. Clinical trial information: NCT02348216.Data-cut; median f/u, mos N = 101 BOR, n (%) ORR Concordance, % Local IRC ORR CR ORR CR PA; 8.7 83 (82) 55 (54) 72 (71) 52 (51) 77 YESCARTA USPI; 11.6 84 (83) 55 (54) 73 (72) 52 (51) 79 LTFU; 15.1 84 (83) 59 (58) 73 (72) 52 (51) 79
The inositol 1,4,5-trisphosphate-forming agonist histamine activates a ryanodine-sensitive Ca2+ release mechanism in bovine adrenal chromaffin cells. (1991)

The role of a Ca(2+)-induced Ca2+ release (CICR) mechanism in the generation of agonist-induced increases of intracellular free Ca2+ concentration ([Ca2+]i) was studied in bovine adrenal chromaffin cells. In single cells, repetitive stimulations with caffeine at 200-s intervals evoked reproducible spikes of [Ca2+]i. Ryanodine, an agent that interacts with the CICR channel of muscle, inhibited the caffeine-induced spikes of [Ca2+]i in a "use-dependent" way. High affinity binding sites for [3H]ryanodine (Kd 3.3 nM, Bmax 26 fmol/mg protein) were also detected in membranes from chromaffin cells, supporting the presence of a caffeine- and ryanodine-sensitive CICR channel. Pretreatment of single cells with caffeine + ryanodine to reduce the size of the caffeine-sensitive Ca2+ compartment inhibited a subsequent spike of [Ca2+]i evoked by histamine, a D-myo-inositol 1,4,5-trisphosphate-forming agonist. This demonstrates that a significant portion of the Ca2+ released by histamine comes from a caffeine- and ryanodine-sensitive pool. Ryanodine inhibited by 50% the size of [Ca2+]i spikes evoked by repetitive stimulation with histamine and did so in a use-dependent manner. These data suggest that, in addition to D-myoinositol 1,4,5-trisphosphate, activation of a caffeine- and ryanodine-sensitive CICR channel participates in the generation of histamine-induced release of intracellular Ca2+.
COORDINATORs: TAEMS Modeling and Interfacing for First Response. (2005)

The number and kind of threats to life and property in an emergency situation is immense. Couple the magnitude of the potential threats with their typically rapid evolution from first detection to response, and the need for fast, coordinated response is apparent. This need is only increased by the threat of chemical, biological, or nuclear terrorist acts. The wide array of potential threats together with the dynamism of emergency situations shows the importance of efficient and effective emergency response team coordination and highlights the need for flexible, semi-autonomous decision support aids. This paper describes the application of TAEMS agent technology to the problem of coordinating distributed emergency response teams. We present the technology application through an emergency response scenario and offer thoughts on extending TAEMS agent technology to better suit the needs of today’s emergency responders.
PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition (2014)

http://plaac.wi.mit.edu/. The Ruby-based web framework and the command-line software (implemented in Java, with visualization routines in R) are available at http://github.com/whitehead/plaac under the MIT license. All software can be run under OS X, Windows and Unix.
Optimizing Power Transfer Efficiency and Bandwidth for Near Field Communication Systems (2012)

Near-field communication (NFC) is a specification for short-range wireless links operating at 13.56 MHz in the high-frequency (HF) band. The achievable bandwidth, efficiency, and range of lightweight, size-constrained, low-power NFC systems are limited by fundamental theorems of small antenna theory. We develop a relationship between near field power transfer and radiation efficiency for dipole-type antennas, which is applicable to both communications and wireless power transfer applications, and present modeled and experimentally measured results for the bandwidth efficiency product of two ferrite loop antenna designs. The model is used to determine the optimal geometrical parameters that maximize this figure of merit for a given antenna size. Modeled and measured results show that ferrite loops can approach theoretical limits on performance for the bandwidth efficiency product of an antenna with a given size.
Evaluating the protective role of ischaemic preconditioning in rat hearts using a stationary small-animal SPECT imager and 99mTc-glucarate (2008)

IPC offers cardioprotection and relates to the activation of adenosine receptors in rat hearts. FastSPECT GLA imaging is not only useful in detecting early ischaemia-reperfusion injury, but also valuable in evaluating cardioprotection.