gebhart/patrepeval huggingface dataset:
Chronic graft-versus-host disease in pancreas after kidney transplant recipients – An unrecognized entity (2020)

Graft-versus-host disease (GVHD), a common complication after peripheral blood stem cell or bone marrow transplantation, rarely occurs in kidney and pancreas transplant recipients. The true incidence may be confounded by the rarity of the disorder, with a resultant lack of appreciation of the diagnosis as a potential cause of common clinical manifestations such as cytopenias and immune dysfunction. Reports of GVHD in kidney and pancreas transplant recipients almost uniformly describe patients in the early posttransplant period (days to months) with the typical manifestations of acute GVHD involving the skin, liver, and intestines. In contrast, reports of solid organ transplant recipients with clinical features more consistent with chronic GVHD (cGVHD) are lacking, raising concern of underrecognition of this severe complication. Occurrence later after transplant may be even more likely to result in lack of recognition. We report 2 cases of possible cGVHD occurring in recipients of pancreas after kidney transplantation, which were diagnosed at 5.5 and 42 months after pancreas transplant. Both patients presented with severe pancytopenia, multiple opportunistic infections, and features suggestive of cGVHD. Transplant professionals should be aware of the possibility of acute and cGVHD in pancreas after kidney transplant recipients and be able to recognize the clinical manifestations.
Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism (2018)

Summary We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.
Succinic Acid Adsorption from Fermentation Broth and Regeneration (2004)

More than 25 sorbents were tested for uptake of succinic acid from aqueous solutions. The best resins were then tested for successive loading and regeneration using hot water. The key desired properties for an ideal sorbent are high capacity, complete stable regenerability, and specificity for the product. The best resins have a stable capacity of about 0.06 g of succinic acid / g of resin at moderate concentrations (1–5 g/L) of succinic acid. Several sorbents were tested more exhaustively for uptake of succinic acid and for successive loading and regeneration using hot water. One resin, XUS 40285, has a good stable isotherm capacity, prefers succinate over glucose, and has good capacities at both acidic and neutral pH. Succinic acid was removed from simulated media containing salts, succinic acid, acetic acid, and sugar using a packed column of sorbent resin, XUS 40285. The fermentation byproduct, acetate, was completely separated from succinate. A simple hot water regeneration successfully concentrated succinate from 10 g/L (inlet) to 40–110 g/L in the effluent. If successful, this would lower separation costs by reducing the need for chemicals for the initial purification step. Despite promising initial results of good capacity (0.06 g of succinic / g of sorbent), 70% recovery using hot water, and a recovered concentration of >100 g/L, this regeneration was not stable over 10 cycles in the column. Alternative regeneration schemes using acid and base were examined. Two (XUS 40285 and XFS-40422) showed both good stable capacities for succinic acid over 10 cycles and >95% recovery in a batch operation using a modified extraction procedure combining acid and hot water washes. These resins showed comparable results with actual broth.
Conformational Constraint of Mammalian, Chicken, and Salmon GnRHs, But Not GnRH II, Enhances Binding at Mammalian and Nonmammalian Receptors: Evidence for Preconfiguration of GnRH II (2002)

Mammalian GnRH (mGnRH) is believed to interact with mGnRH type I receptors in a beta-II' turn conformation involving residues 5-8. This conformation can be constrained by substitution of a D-amino acid at position 6 or by a lactam ring involving residues 6 and 7, thereby increasing receptor binding affinity. It has been proposed that this is not the case for non-mGnRH receptors. However, we show that this conformational constraint increases the binding affinity of mammalian, chicken, and salmon GnRH for the chicken and catfish receptors, as well as for the mouse receptor. Therefore, we conclude that the beta-II' turn conformation enhances ligand binding for non-mGnRH as well as mGnRH type I receptors. In contrast, most substitutions of a D-amino acid in position 6 have limited effect on binding affinity for GnRH II. We suggest that this ligand is preconfigured through intramolecular interactions, which accounts for its high binding affinity and total conservation of primary structure over 500 million years of evolution.
Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats (2019)

Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (<i>n</i> = 9) and Sham (<i>n</i> = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN.
Cell Search Time Performance Using Multipath Signals in LTE Downlink (2011)

This paper presents cell search time performance using multipath signals in the Long-Term Evolution (LTE) downlink employing Orthogonal Frequency Division Multiple Access (OFDMA) in inter-cell site asynchronous operation. In the paper, we propose primary synchronization signal (PSS) detection using multipath signals based on window detection and secondary synchronization signal (SSS) detection using coherent summation of channel estimates weighted by the frequency domain channel response of typically assumed multipath signals. Computer simulation results show that the effect of using multipath signals for PSS detection on the overall cell search time performance is slight, and the maximum correlation peak detection for the PSS provides a sufficiently fast cell search time. The results also show that coherent averaging of channel estimates using the PSS to detect the eNode-B-specific SSS sequence is effective in achieving a fast cell search time, and the achievable cell search time is insensitive to the weighting factor as long as the interval of the coherent summation is optimized for the respective power delay profiles.
Abstract 1086: Immune checkpoint inhibitors CD300A and LAIR1 are associated with poor prognosis in clear cell renal cell carcinoma (2019)

Abstract Immune checkpoint inhibitors targeting the programmed cell death-1 receptor (PD-1) have been shown to improve the survival of patients with clear cell renal cell carcinoma (CCRCC). However, a benefit for CCCRC patients was observed with the FDA-approved PD-1 inhibitor Nivolumab irrespective of PD-1 ligand (PD-L1) expression status indicating there are potentially additional CCRCC checkpoint molecules worth exploring for targeted therapy. We therefore analyzed RNAseq data (n=534, CCRCCs; n=72, normal kidney specimens) from the TCGA project, and found that PD-L1 was not upregulated in CCRCC when compared to normal tissue whereas other checkpoint members i.e. CD300A and LAIR1 were among the most significantly upregulated genes in CCRCCs. In terms of overall survival, high expression of PD-L1 was associated with better outcome in CCRCCs while high expression of CD300A and LAIR1 were significantly associated with worse outcomes. We confirmed these findings in two independent cohorts of CCRCC patients. Furthermore, we performed cell type enrichment analysis, which showed that CD300A and LAIR1 are most likely expressed by tumor-associated macrophages in the CCRCC tumor microenvironment. Our results suggest that PD1/PDL1 might be suboptimal targets in CCRCC and that there are additional unexplored immune checkpoint molecules that warrant our attention. Note: This abstract was not presented at the meeting. Citation Format: Jonas Sjolund, David Lindgren, Helén Nilsson, Martin E. Johansson, Hakan Axelson, Kristian Pietras. Immune checkpoint inhibitors CD300A and LAIR1 are associated with poor prognosis in clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1086.
Alterations in renal tubular water transport induced by parathyroid hormone: evidence for both antidiuretic hormone-mediated and independent effects. (1982)

Abstract The renal tubular effects of PTH and ADH are both mediated by cyclic AMP. Furthermore, both of these agents in pharmacological dosage inhibit phosphate reabsorption in the proximal nephron. Although the effect of ADH on tubular water transport is well documented, the actions of PTH on this tubular function have not been studied. We therefore examined the action of PTH on water reabsorption in conscious, chronically TPTX dogs undergoing maximal steady-state water diuresis. The effects of a supraphysiological amount of the hormone (3 to 5 U/kg) were compared to those produced by a dose of PTH (0.3 to 0.5 U/kg) that restores phosphate excretion to a level seen in normal intact animals. In physiological dosage, PTH increased V from 5.6 ± 0.5 to 6.4 ± 0.5 ml/min (p H 2 O as well as C H 2 O factored for GFR × 100 from 4.26 ± 0.39 to 4.88 ± 0.40 ml/min (p H 2 O and CH2OGFR × 100: 4.70 ± 0.33 → 1.76 ± 0.36 ml/min (p AVP levels rose in three of six animals in which it was measured during high-dose PTH infusion, but the levels were falling at a time when urinary osmolality continued to rise. Furthermore, in vitro, PTH and ADH cross-reacted. That is, PTH largely stimulated cortical cyclic AMP, and ADH increased the production of the nucleotide primarily in the medulla. However, in large dosage PTH activated adenylate cyclase in the medulla, and ADH increased the cortical production of cyclic AMP. When PTH was administered in pharmacological dosage to TPTX, hypophysectomized dogs undergoing maximal water diuresis, there was no change in tubular water transport. We conclude the following from these data. (1) PTH, in pharmacological dosage, has an ADH-like effect on renal tubular water transport. (2) This action of PTH does not appear to be consistently related to the measurable release of ADH but (3) seems most likely due to an effect of PTH on medullary adenylate cyclase with subsequent alterations in the permeability of the tubular epithelium to water.
Changes of HCN gene expression and If currents in Nkx2.5-positive cardiomyocytes derived from murine embryonic stem cells during differentiation (2008)

Changes in the expression of hyperpolarization-activated cyclic nucleotide (HCN)-gated channels and I(f) currents during the differentiation of embryonic stem cells into cardiac cells remain unknown. We examined changes of HCN genes in expression and function during the differentiation of Nkx2.5-positive cardiac precursor cells derived from mouse ES cells using cell sorting, RTPCR, immunofluorescence and whole cell patch-clamp techniques. Cs(+)-induced inhibition of automaticity and transcription of HCN genes increased during differentiation. Expressions of Nkx2.5, a marker of cardiac progenitor cell, and Flk1, a marker of hemangioblast, were mutually exclusive. Messenger RNA and proteins encoded by HCN1 and 4 genes were predominantly observed in Nkx2.5-positive cells on day 15, although Flk1-positive cells did not express genes of the HCN family on that day. Cs(+)-induced prolongation of the cycle of spontaneous action potentials and I(f) currents were predominantly observed on day 15. These results suggested that a fraction of Nkx2.5-positive cardiac precursor cells was committed to pacemaking cells expressing I(f) channels predominantly encoded by HCN 1 and 4 genes.
A Biomechanical Evaluation of an Anatomical Coracoclavicular Ligament Reconstruction (2005)

A more anatomical reconstruction using a free tendon graft of both the trapezoid and conoid ligaments may provide a stronger, permanent biologic solution for dislocation of the acromioclavicular joint. This reconstruction may minimize recurrent subluxation and residual pain and permit earlier rehabilitation.
Global organization of three-dimensional, volume-preserving flows: Constraints, degenerate points, and Lagrangian structure (2020)

Global organization of three-dimensional (3D) Lagrangian chaotic transport is difficult to infer without extensive computation. For 3D time-periodic flows with one invariant, we show how constraints on deformation that arise from volume-preservation and periodic lines result in resonant degenerate points that periodically have zero net deformation. These points organize all Lagrangian transport in such flows through coordination of lower-order and higher-order periodic lines and prefigure unique transport structures that arise after perturbation and breaking of the invariant. Degenerate points of periodic lines and the extended 3D structures associated with them are easily identified through the trace of the deformation tensor calculated along periodic lines. These results reveal the importance of degenerate points in understanding transport in one-invariant fluid flows.
Cascaded plasmon-plasmon coupling mediated energy transfer across stratified metal-dielectric nanostructures (2016)

Surface plasmon (SP) coupling has been successfully applied to nonradiative energy transfer via exciton-plasmon-exciton coupling in conventionally sandwiched donor-metal film-acceptor configurations. However, these structures lack the desired efficiency and suffer poor photoemission due to the high energy loss. Here, we show that the cascaded exciton-plasmon-plasmon-exciton coupling in stratified architecture enables an efficient energy transfer mechanism. The overlaps of the surface plasmon modes at the metal-dielectric and dielectric-metal interfaces allow for strong cross-coupling in comparison with the single metal film configuration. The proposed architecture has been demonstrated through the analytical modeling and numerical simulation of an oscillating dipole near the stratified nanostructure of metal-dielectric-metal-acceptor. Consistent with theoretical and numerical results, experimental measurements confirm at least 50% plasmon resonance energy transfer enhancement in the donor-metal-dielectric-metal-acceptor compared to the donor-metal-acceptor structure. Cascaded plasmon-plasmon coupling enables record high efficiency for exciton transfer through metallic structures.
Surface Drifter Observations From the Arctic Ocean's Beaufort Sea: Evidence for Submesoscale Dynamics (2018)

Abstract Position and velocity data are analyzed from a release of surface ocean drifters in the Arctic Ocean's Beaufort Sea in ice‐free conditions. Position information is returned at sufficiently high frequency to allow for the investigation of surface‐ocean flows ranging from around 0.5 km in lateral scale (submesoscale, SM, flows) to flows that are tens of kilometers in horizontal extent. Lagrangian statistics from the drifter release are analyzed in conjunction with Eulerian (ship‐based) measurements of surface ocean temperature and salinity. Results show dynamics that are largely consistent with flows at similar scales in the midlatitude oceans. Horizontal wavenumber k spectra of density in the surface ocean scale as , consistent with energetic SM flows. Lagrangian drifters indicate local dispersion in the surface ocean layer at horizontal scales smaller than 10 km, which confirms the presence of active submesoscale dynamics. Features at these scales give rise to lateral diffusivities (in the range 1–10 3 m 2 s −1 ) of similar range to values inferred in the midlatitudes. Velocity structure functions present an energy‐cascade inertial range at submesoscales with indication of a transition to a forward energy cascade at scales smaller than 1 km confirming the transition to 3‐D turbulence. The active SM flow‐field drives enhanced lateral and vertical fluxes in the Arctic Ocean mixed layer, which has first‐order implications to the transport of heat, sea‐ice floes, nutrients, and contaminants.
Synthesis of biocompatible and thermally sensitive poly(N-vinylcaprolactam) nanogels via inverse miniemulsion polymerization: Effect of the surfactant concentration Part A Polymer chemistry (2010)

The goal of this study was to develop a new route to prepare thermally responsive polymer nanogels. Poly(N-vinylcaprolactam) nanogels were prepared via inverse miniemulsion polymerization (W/O) at 70 °C using n-hexadecane as a nonpolar continuous phase, potassium persulfate as an initiator, and N,N′-methylenebisacrylamide as a crosslinker. Sorbitan monooleate (Span 80) was used as surfactant and its influence on the polymerization kinetics and on the colloidal characteristics of the nanogels were principally investigated. It was observed that the addition of a strong lipophobe is required to stabilize the resulting miniemulsion. The nanogels were characterized in terms of morphology, size, zeta potential, and thermoproperties using transmission electron microscopy and dynamic light scattering. It was observed that all the nanogels obtained collapsed when the lower critical solution temperature (LCST) was raised.
TG7r1 channel model document for high rate PD communications (2015)

Purpose Providing channel models which allow a fair comparison of different physical layer (PHY) High Rate PD Communications proposals submitted to TG7r1 in response to the Call for Proposals (CFP). Notice This document has been prepared to assist the IEEE P802.15. It is offered as a basis for discussion and is not binding on the contributing individual(s) or organization(s). The material in this document is subject to change in form and content after further study. The contributor(s) reserve(s) the right to add, amend or withdraw material contained herein.
Quantifying risky behavior in surgical simulation. (2005)

Evaluating a trainee's performance on a simulated procedure involves determining whether a specified objective was met while avoiding certain "injurious" actions that damage vulnerable structures. However, it is also important to teach the stylistic behaviors that minimize overall risk to the patient, even though these criteria may be more difficult to explicitly specify and detect. In this paper, we address the development of metrics that evaluate the risk in a trainee's behavior while performing a simulated mastoidectomy. Specifically, we measure the trainee's ability to maintain an appropriate field of view so as to avoid drilling bone that is hidden from view, as well as to consistently apply appropriate forces and velocities. Models of the maximum safe force and velocity magnitudes as functions of distances from key vulnerable structures are learned from model procedures performed by an expert surgeon on the simulator. In addition to quantitatively scoring the trainee's performance, these metrics allow for interactive 3D visualization of the performance by distinctive coloring of regions in which excessive forces or velocities were applied or insufficient visibility was maintained, enabling the trainee to pinpoint his/her mistakes and how to correct them. Although these risky behaviors relate to a mastoidectomy simulator, the objectives of maintaining visibility and applying safe forces and velocities are common in surgery, so it may be possible to extend much of this methodology to other procedures.
A direct-acting antiviral drug abrogates viremia in Zika virus–infected rhesus macaques (2020)

Zika virus infection in humans has been associated with serious reproductive and neurological complications. At present, no protective antiviral drug treatment is available. Here, we describe the testing and evaluation of the antiviral drug, galidesivir, against Zika virus infection in rhesus macaques. We conducted four preclinical studies in rhesus macaques to assess the safety, antiviral efficacy, and dosing strategies for galidesivir (BCX4430) against Zika virus infection. We treated 70 rhesus macaques infected by various routes with the Puerto Rico or Thai Zika virus isolates. We evaluated galidesivir administered as early as 90 min and as late as 72 hours after subcutaneous Zika virus infection and as late as 5 days after intravaginal infection. We evaluated the efficacy of a range of galidesivir doses with endpoints including Zika virus RNA in plasma, saliva, urine, and cerebrospinal fluid. Galidesivir dosing in rhesus macaques was safe and offered postexposure protection against Zika virus infection. Galidesivir exhibited favorable pharmacokinetics with no observed teratogenic effects in rats or rabbits at any dose tested. The antiviral efficacy of galidesivir observed in the blood and central nervous system of infected animals warrants continued evaluation of this compound for the treatment of flaviviral infections.