gebhart/patrepeval huggingface dataset:
Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR (2007)

PKR is an interferon (IFN)-induced protein kinase, which is involved in regulation of antiviral innate immunity, stress signaling, cell proliferation and programmed cell death. Although a low amount of PKR is expressed ubiquitously in all cell types in the absence of IFNs, PKR expression is induced at transcriptional level by IFN. PKR's enzymatic activity is activated by its binding to one of its activators. Double-stranded (ds) RNA, protein activator PACT and heparin are the three known activators of PKR. Activation of PKR in cells leads to a general block in protein synthesis due to phosphorylation of eIF2alpha on serine 51 by PKR. PKR activation is regulated very tightly in mammalian cells and a prolonged activation of PKR leads to apoptosis. Thus, positive and negative regulation of PKR activation is important for cell viability and function. The studies presented here describe human dihydrouridine synthase-2 (hDUS2) as a novel regulator of PKR. We originally identified hDUS2 as a protein interacting with PACT in a yeast two-hybrid screen. Further characterization revealed that hDUS2 also interacts with PKR through its dsRNA binding/dimerization domain and inhibits its kinase activity. Our results suggest that hDUS2 may act as a novel inhibitor of PKR in cells.
Bevacizumab Inhibits Breast Cancer-Induced Osteolysis, Surrounding Soft Tissue Metastasis, and Angiogenesis in Rats as Visualized by VCT and MRI (2008)

The aim of this study was to evaluate the effect of an antiangiogenic treatment with the vascular endothelial growth factor antibody bevacizumab in an experimental model of breast cancer bone metastasis and to monitor osteolysis, soft tissue tumor, and angiogenesis in bone metastasis noninvasively by volumetric computed tomography (VCT) and magnetic resonance imaging (MRI). After inoculation of MDA-MB-231 human breast cancer cells into nude rats, bone metastasis was monitored with contrast-enhanced VCT and MRI from day 30 to day 70 after tumor cell inoculation, respectively. Thereby, animals of the treatment group (10 mg/kg bevacizumab IV weekly, n = 15) were compared with sham-treated animals (n = 17). Treatment with bevacizumab resulted in a significant difference versus control in osteolytic as well as soft tissue lesion sizes (days 50 to 70 and 40 to 70 after tumor cell inoculation, respectively; P < .05). This observation was paralleled with significantly reduced vascularization in the treatment group as shown by reduced increase in relative signal intensity in dynamic contrast-enhanced MRI from days 40 to 70 (P < .05). Contrast-enhanced VCT and histology confirmed decreased angiogenesis as well as new bone formation after application of bevacizumab. In conclusion, bevacizumab significantly inhibited osteolysis, surrounding soft tissue tumor growth, and angiogenesis in an experimental model of breast cancer bone metastasis as visualized by VCT and MRI.
Anterior cruciate ligament replacements: A mechanical study of femoral attachment location, flexion angle at tensioning, and initial tension (1990)

Abstract We examined three surgical variables that affect the ability of an anteior cruciate ligament replacement to restore the limit of anterior tibial translation. These were the placement site of the substitute on the femur, the initial tension applied to the replacement, and the flexion angle of the knee at the time of tensioning. An anterior load of 100 N was applied to the tibia. As the knee was flexed, we measured the tensile force in the substitute and the anteroposterior position of the femur relative to the tibia. Placement largely determined whether the force in the replacement increased or decreased with flexion. Placement also largely determined whether the tibia moved anteriorly or posteriorly with flexion compared to its position in the intact knee. The initial tension and the flexion angle at tensioning affected the magnitude of force in the substitute and the magnitude of the change in AP position. They did not affect how force and AP position changed with flexion. Greater increases in force and greater posterior shifts in tibial position were produced by changing the flexion angle at tensioning from 0° to 30° than by increasing the initial tension from 22 to 44 N.
Gasless laparoendoscopic single-site surgery for management of unruptured tubal pregnancy in a woman with moderate COVID-19 pneumonia after administration of remdesivir and casirivimab-imdevimab: A case report (2021)

Laparoscopic surgery, preceded by anti-viral therapy for COVID-19, is a feasible option for the management of hemodynamically stable tubal pregnancy in a woman with moderate COVID-19 pneumonia.
Aliphatic Long‐Chain C20 Polyesters from Olefin Metathesis (2011)

Self-metathesis of undecenoic acid with [(PCy3)2Cl2Ru=CHPh] (2), followed by exhaustive hydrogenation yielded pure 1,20-eicosanedioic acid (5) (>99%) free of side-products from isomerization. Polycondensation with eicosane-1,20-diol (6), formed by reduction of the diol, yielded polyester 20,20 (Tm = 108 °C). By comparison, the known ADMET polymerization of undec-10-enyl undec-10-enoate (7), and subsequent exhaustive polymer-analogous hydrogenation yielded a polyester (poly-8) with irregular structure of the ester groups in the polymer chain (-O(C=O)- vs. -C(=O)O-) (Tm = 103 °C). Hydrogenation of secondary dispersions of poly-7 yielded aqueous dispersions of the long-chain aliphatic polyester poly-8.
Identification of human endomucin‐1 and ‐2 as membrane‐bound O‐sialoglycoproteins with anti‐adhesive activity1 (2001)

Using a signal sequence trap method and database search, we identified a series of human cDNAs encoding two structurally related type I membrane proteins of approximately 25 kDa with multiple glycosylation motifs. These genes, termed endomucin-1/-2, are expressed in several human tissues including heart, kidney, and lung. Exogenously expressed human endomucin-1/-2 proteins were modified into 80-120 kDa glycoproteins, which were susceptible to O-sialoglycoprotein endopeptidase digestion. Transient overexpression of endomucin-1/-2 reduced the number of adhesion plaques and reduced cell attachment to the substrate. This phenotype was suppressed by laminin or the protein kinase inhibitor staurosporine. Our findings suggest that human endomucin-1/-2 negatively regulate cell adhesion to the extracellular matrix.
A 200 MHz RISC microprocessor with 128 kB on-chip caches (2002)

The 32b PA-RISC 1.1 microprocessor features 64kB, two-way set-associative instruction and data caches on-chip, a controller for off-chip second-level cache of 256kB to 64MB, and an on-chip main memory and I/O controller. It operates up to 200MHz, with performance of 7.75 SPECint95 and 7.56 SPECfp95 in a 16OMHz system. The processor core is leveraged from a previous design, with circuit, fabrication process, and microarchitecture enhancements for improved performance and reduced power consumption. Circuit design allows high-frequency operation in the 0.5/spl mu/m, 3.3V CMOS process.
Artificial Neural Networks Can be Used as Alternative Method to Estimate Loss Tooth Root Sizes for Prediction of Dental Implants (2017)

The aim of this study was to investigate the feasibility of estimation of canine root length and cervical width by an artificial neural network method with an appropriate setting. We randomly obtained 120 representative samples of routine panoramic radiographs by computer tomography (CT). Of 120 samples, 96 (80%) were used in training phase and 24 (20%) were used in test phase after a randomized selection. The intertuberal length (IL) of maxilla and canine root length (RL) and canine root cervical width (CW) of the right canine tooth was measured and was entered to a datum file. According to the results, the method is convenient with this purpose. The mean square error values are lied between 2% and 4.4% for the estimations. This shows that ANN is an alternative method for the prediction of canine root length and cervical width. Since an ANN software, as a cost-effective tool that can be purchased and after a training procedure that can be easily performed by an experienced person, the ANN system can have a place in implant surgery after further studies and optimization of software setting. An ANN software can be adapted to the dental implant surgery after proper setting and training procedures that can be easily performed by an experienced person and it can have a place in implant surgery after further expanded studies and optimization of software setting.
Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans (2005)

Chronic infection with hepatitis B virus (HBV) is associated with the majority of hepatocellular carcinoma (HCC). The diagnosis of HCC is usually made in the late stages of the disease, when treatment options are limited and prognosis is poor. We therefore have developed a method of glycoproteomic analysis in an attempt to discover serum markers that can assist in the early detection of HBV-induced liver cancer. Briefly, a comparative method for analysis of oligosaccharides released from serum glycoproteins and for recovery and identification of proteins with aberrant glycosylation, as a function of cancer diagnosis, is described. The model we have used is the woodchuck (Marmota monax), which shares similarities in the glycosylation pattern associated with liver proteins in human HCC. In this report, we show that woodchucks diagnosed with HCC have dramatically higher levels of serum-associated core alpha-1,6-linked fucose, as compared with woodchucks without a diagnosis of HCC. The coupling of this methodology with 2D gel proteomics has permitted the identification of several glycoproteins with altered glycosylation as a function of cancer. One such glycoprotein, Golgi Protein 73 (GP73), was found to be elevated and hyperfucosylated in animals with HCC. Further, the study showed GP73 to be elevated in the serum of people with a diagnosis of HCC, providing a validation of our approach. The potential of this technology for biomarker discovery and the implications of increased levels of GP73 in liver cancer are discussed.
Assessment of the Psychometric Properties of a Questionnaire Assessing Patient-Reported Outcomes With Laser In Situ Keratomileusis (PROWL) (2016)

The results of these studies support the reliability and validity of visual symptom scales to evaluate the effects of LASIK surgery in future studies.
Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster. (1987)

DNA sequences involved in the control of the developmental and spatial expression of the yellow locus of Drosophila were identified by phenotypic analysis of germline transformants carrying various in vitro modified yellow genes. Two regions, located between -2873 bp and -1868 bp and between -1868 bp and -700 bp, act as tissue-specific enhancers which respectively regulate yellow transcription in the wings and body of the adult flies. Sequences situated closer to the mRNA cap site, between -225 bp and -91 bp from the start of transcription, are responsible for yellow expression in the denticle belts and mouth parts during larval development. Finally, coloration of the adult bristles is regulated by sequences located in the intron of the yellow gene. These results indicate the existence of several separate DNA elements responsible for the different patterns of temporal and spatial expression of the yellow locus.
First-in-human phase I study of HPN424, a tri-specific half-life extended PSMA-targeting T-cell engager in patients with metastatic castration-resistant prostate cancer (mCRPC). (2020)

5552 Background: HPN424 is a first-in-class, prostate-specific membrane antigen (PSMA)-targeting T-cell engager designed as a small, globular protein to enable efficient solid-tumor penetration with prolonged half-life. HPN424 is derived from the TriTAC platform (Tri-specific T-Cell-Activating Construct) and engineered with three binding domains: anti-PSMA for tumor cell engagement, anti-albumin for half-life extension and anti-CD3 for T-cell engagement. Methods: This Ph I study is evaluating HPN424 in progressing mCRPC patients (pts) who have received &gt;2 prior systemic therapies. Primary endpoints are safety, tolerability and determination of MTD/RP2D. Secondary objectives are pharmacokinetics (PK), pharmacodynamics, immunogenicity, and preliminary anti-tumor activity. HPN424 is administered IV once weekly. Tumor assessments include PSA, CT, and bone scans every 9 weeks. Results: As of 1/17/20, 27 pts were dosed in 8 cohorts ranging from 1.3 to 72ng/kg. Pts received a median of 6 prior systemic regimens, including &gt;1 novel AR therapy, and 59% received prior chemotherapy for mCRPC. Median PSA at baseline was 251 ng/mL (range: 0.05 – 5000). No DLTs have been observed. The most common grade &gt;3 TRAEs were cytokine release syndrome (CRS) (3 pts) and transient elevated liver transaminases (2 pts) that occurred concurrently with CRS. All CRS events resolved and pts were successfully re-treated. Short-term steroid premedication was effective in limiting CRS and allowing long-term weekly treatment. HPN424 demonstrated dose proportional increase in Cmax and AUC with a geometric mean T1/2 of 30.5 hours. Dose-dependent, transient increases in peripheral cytokine and chemokine levels were observed. Reduction in circulating tumor cells (CTCs) was seen in 11 of 19 pts with measurable CTC at baseline. Six pts had PSA decreases from baseline ranging from -3.8% to -76%, including 2 pts with PSA decline ≥50%. Ten of 20 pts (50%) with &gt; 18 weeks follow-up remained on study beyond week 18 and includes 8 pts on study &gt; 24 weeks. Conclusions: HPN424 represents a novel half-life extended PSMA-targeting T-cell engager that can be safely administered once weekly. AEs have been transient and manageable. Cytokine increases indicate T-cell activation. CTC reductions in subset of pts suggest target engagement. Early signs of clinical activity include PSA reductions and time on study, including 8 pts on study &gt; 24 weeks. Dose escalation is ongoing, including exploration of step dosing. Clinical trial information: NCT03577028 .
Neurobeachin: A Protein Kinase A-Anchoring,beige/Chediak-Higashi Protein Homolog Implicated in Neuronal Membrane Traffic (2000)

We describe the identification and initial characterization of neurobeachin, a neuron-specific multidomain protein of 327 kDa with a high-affinity binding site (K(d), 10 nm) for the type II regulatory subunit of protein kinase A (PKA RII). Neurobeachin is peripherally associated with pleomorphic tubulovesicular endomembranes near the trans sides of Golgi stacks and throughout the cell body and cell processes. It is also found in a subpopulation of synapses, where it is concentrated at the postsynaptic plasma membrane. In live cells, perinuclear neurobeachin is dispersed by brefeldin A (BFA) within 1 min, and in permeabilized cells a recruitment of neurobeachin from cytosol to Golgi-near membranes is stimulated by GTPgammaS and prevented by brefeldin A. Spots of neurobeachin recruitment are close to but distinct from recruitment sites of COP-I, AP-1, and AP-3 coat proteins involved in vesicle budding. These observations indicate that neurobeachin binding to membranes close to the trans-Golgi requires an ADP-ribosylation factor-like GTPase, possibly in association with a novel type of protein coat. A neurobeachin isoform that does not bind RII, beige-like protein (BGL), is expressed in many tissues. Neurobeachin, BGL, and approximately 10 other mammalian gene products share a characteristic C-terminal BEACH-WD40 sequence module, which is also present in gene products of invertebrates, plants, protozoans, and yeasts, thus defining a new protein family. The prototype member of this family of BEACH domain proteins, lysosomal trafficking regulator (LYST), is deficient in genetic defects of protein sorting in lysosome biogenesis (the beige mouse and Chediak-Higashi syndrome). Neurobeachin's subcellular localization, its coat protein-like membrane recruitment, and its sequence similarity to LYST suggest an involvement in neuronal post-Golgi membrane traffic, one of its functions being to recruit protein kinase A to the membranes with which it associates.
AFM, SEM andin situRHEED study of Cu texture evolution on amorphous carbon by oblique angle vapor deposition (2005)

The evolution of the crystal orientation of a Cu film grown on an amorphous carbon substrate without intentional heating under $75\ifmmode\pm\else\textpm\fi{}6\ifmmode^\circ\else\textdegree\fi{}$ oblique angle vapor deposition was investigated ex-situ by atomic force microscopy (AFM) and scanning electron microscopy (SEM), and in-situ by reflection high-energy electron diffraction (RHEED). At the initial stage of growth ($&lt;\ensuremath{\sim}12\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$ thick) the diffraction patterns showed uniform rings indicating random nucleations of crystals. With more Cu depositions ($&gt;\ensuremath{\sim}100\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$ thick) the diffraction pattern started to break symmetrically from the middle of the (111) and (200) rings representing the absence of (111) and (200) planes parallel to the substrate. However, after this transition stage, at the thickness of $\ensuremath{\sim}410\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$, the intensity distribution of diffraction patterns appeared asymmetric about the middle of the rings, which is interpreted as the appearance of a tilted (111) texture. Finally the diffraction patterns developed into separated short arcs and showed only a $⟨111⟩⟨\overline{1}10⟩$ II-O (two-orientation) texture. By comparing RHEED patterns with the SEM and AFM images of the final film, we argue that the tilted columns having tilted (111) top faces dominate in the later stage of growth. Furthermore, considering the geometry of crystals and shadowing effects, we argue that the vertices of columns having the highest growth velocity normal to the substrate and therefore receiving the maximum flux will dominate the film growth and determine the tilt angle of the texture and the preference of the azimuthal angle orientation.
The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors (2009)

Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US.
Quaternary pilocarpine derivatives as potential acetylcholine antagonists. 2. Alterations in the lactone and imidazole moieties (1976)

In order to investigate the chemical behavior of pilocarpine, as well as the factors which determine its pharmacological activity, systematic and specific structural changes involving the lactone and imidazole moieties have been performed. Series of model compounds with cyclic or open-chain structures and a variety of N-3 bonded chains obtained from previously prepared anticholinergic derivatives of pilocarpine have been synthesized. The changes included N-3 chains of different lengths with an acetylcholine-like structure, the introduction of nucleophilic groups such as ketoxime, hydroxamic, or both at the side chain, or following hydroxylaminolysis of the lactone, respectively. Specific structural alterations could be obtained by reacting with free hydroxylamine under carefully controlled conditions, and the existence of syn and anti isomers was disclosed in certain cases. The new groups in the pilocarpine derivatives influenced their degree of antagonism to acetylcholine. Several compounds displayed some antidotal activity.
Thalidomide for the Treatment of Chronic Graft-versus-Host Disease (1992)

In this preliminary trial, thalidomide appeared to be safe and effective for the treatment of chronic GVHD. A trial comparing thalidomide with prednisone in patients with newly diagnosed chronic GVHD will be required to demonstrate its relative efficacy.
Encapsulation of Neutral Gold Nanoclusters by Resorcinarenes (1999)

A new strategy for encapsulating neutral nanoclusters is presented which employs surfactants with large concave headgroups and multiple contact sites. Au nanoclusters ranging from 3 to 20 nm in diameter were generated in the vapor phase and dispersed into dilute solutions of resorcinarenes 1−3, where they were stabilized for up to several months. The resorcinarenes were readily displaced by dodecanethiol, which resulted in the precipitation of the larger particles as determined by UV−vis absorption spectroscopy and transmission electron microscopy. The chemisorption of resorcinarenes to the Au cluster surface is most likely mediated by multiple Au−O interactions, which is supported by surface-enhanced Raman spectroscopy.
Myosin VI Regulates Endocytosis of the Cystic Fibrosis Transmembrane Conductance Regulator (2004)

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-regulated Cl(-) channel expressed in the apical plasma membrane in fluid-transporting epithelia. Although CFTR is rapidly endocytosed from the apical membrane of polarized epithelial cells and efficiently recycled back to the plasma membrane, little is known about the molecular mechanisms regulating CFTR endocytosis and endocytic recycling. Myosin VI, an actin-dependent, minus-end directed mechanoenzyme, has been implicated in clathrin-mediated endocytosis in epithelial cells. The goal of this study was to determine whether myosin VI regulates CFTR endocytosis. Endogenous, apical membrane CFTR in polarized human airway epithelial cells (Calu-3) formed a complex with myosin VI, the myosin VI adaptor protein Disabled 2 (Dab2), and clathrin. The tail domain of myosin VI, a dominant-negative recombinant fragment, displaced endogenous myosin VI from interacting with Dab2 and CFTR and increased the expression of CFTR in the plasma membrane by reducing CFTR endocytosis. However, the myosin VI tail fragment had no effect on the recycling of endocytosed CFTR or on fluid-phase endocytosis. CFTR endocytosis was decreased by cytochalasin D, an actin-filament depolymerizing agent. Taken together, these data indicate that myosin VI and Dab2 facilitate CFTR endocytosis by a mechanism that requires actin filaments.
A family of user-programmable peripherals with a functional unit architecture (1992)

A family of user-programmable peripherals, utilizing an integration strategy based on a programmable system device (PSD) concept, is described. Specifically, PSD is an efficient and highly configurable integration of high-density memory and LSI level logic blocks. The configurability is derived by providing programmable logic and programmable interconnect. PSDX is the first PSD family of programmable microcontroller peripherals; it integrates 256 kb to 1 Mb of EPROM, 16 kb of SRAM, a 28-input by 42-product term programmable logic device (PLD), and flexible I/O ports. This family is primarily targeted for embedded microcontroller applications. Using one PSD device it is possible to replace all the core peripherals in the system and, as a result, achieve a reduction in components, power dissipation, and overall system cost. The flexible architecture is achieved by providing 46 configuration options, which allows the PSD to interface with virtually any 8- or 16-b microcontroller. The integration is made possible by developing a special configurability and testability scheme. These parts are realized on a 1.2- mu m CMOS EPROM process.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Virtual PC 2007的新特性和不足 (2007)

微软公司凭借最新推出的桌面虚拟机产品Virtual PC 2007，无可争议地成为目前虚拟机市场长久以来居于领导地位的VMware最主要的竞争对手。Virtual PC最大的优势在2007版本中仍然得以保持，它仍然是微软公司送给大家的免费大餐，下载地址：http：／／www．microsoft．com／downloads／details．aspx？