gebhart/patrepeval huggingface dataset:
MET Copy Number Gain Is Associated with Gefitinib Resistance in Leptomeningeal Carcinomatosis of EGFR -mutant Lung Cancer (2017)

Leptomeningeal carcinomatosis occurs frequently in <i>EGFR</i>-mutant lung cancer, and develops acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This study aimed to clarify the mechanism of EGFR-TKI resistance in leptomeningeal carcinomatosis and seek for a novel therapeutic strategy. We examined <i>EGFR</i> mutations, including the T790M gatekeeper mutation, in 32 re-biopsy specimens from 12 leptomeningeal carcinomatosis and 20 extracranial lesions of <i>EGFR</i>-mutant lung cancer patients who became refractory to EGFR-TKI treatment. All the 32 specimens had the same baseline <i>EGFR</i> mutations, but the T790M mutation was less frequent in leptomeningeal carcinomatosis specimens than in extracranial specimens (8% vs. 55%, <i>P</i> < 0.01). To study molecular mechanisms of acquired EGFR-TKI resistance in leptomeningeal carcinomatosis, we utilized our previously developed mouse model of leptomeningeal carcinomatosis with the <i>EGFR</i>-mutant lung cancer cell line PC-9/ffluc cells, in which acquired resistance to gefitinib was induced by continuous oral treatment. Compared with subcutaneously inoculated gefitinib-resistant tumors, the T790M mutation was less frequent in leptomeningeal carcinomatosis that acquired resistance to gefitinib. PC-9/LMC-GR cells were established from the gefitinib-resistant leptomeningeal carcinomatosis model, and they were found to be intermediately resistant to gefitinib and osimertinib (third-generation EGFR-TKI). Although <i>EGFR</i>-T790M was negative, gefitinib resistance of PC-9/LMC-GR cells was related to <i>MET</i> copy number gain with MET activation. Moreover, combined use of EGFR-TKI and crizotinib, a MET inhibitor, dramatically regressed leptomeningeal carcinomatosis with acquired resistance to gefitinib or osimertinib. These findings suggest that combination therapy with MET inhibitors may be promising for controlling leptomeningeal carcinomatosis that acquires resistance to EGFR-TKIs. <i>Mol Cancer Ther; 16(3); 506-15. ©2017 AACR</i>.
Implications for a gesture design tool (1999)

Interest in pen-based user interfaces is growing rapidly. One potentially useful feature of pen-based user interfaces is gestures, that is, a mark or stroke that causes a command to execute. Unfortunately, it is difficult to design gestures that are easy 1) for computers to recognize and 2) for humans to learn and remember. To investigate these problems, we built a prototype tool typical fo those used for designing gesture sets. An experiment was then performed to gain insight into the gesture design process and to evaluate this style of tool. The experiment confirmed that gesture design is very difficult and suggested several ways in which current tools can be improved. The most important improvement is to make the tools more active and provide more guidance for designers. This paper describes the gesture design tool, the experiment, and its results.
On joining and caching stochastic streams (2005)

We consider the problem of joining data streams using limited cache memory, with the goal of producing as many result tuples as possible from the cache. Many cache replacement heuristics have been proposed in the past. Their performance often relies on implicit assumptions about the input streams, e.g., that the join attribute values follow a relatively stationary distribution. However, in general and in practice, streams often exhibit more complex behaviors, such as increasing trends and random walks, rendering these "hardwired" heuristics inadequate.In this paper, we propose a framework that is able to exploit known or observed statistical properties of input streams to make cache replacement decisions aimed at maximizing the expected number of result tuples. To illustrate the complexity of the solution space, we show that even an algorithm that considers, at every time step, all possible sequences of future replacement decisions may not be optimal. We then identify a condition between two candidate tuples under which an optimal algorithm would always choose one tuple over the other to replace. We develop a heuristic that behaves consistently with an optimal algorithm whenever this condition is satisfied. We show through experiments that our heuristic outperforms previous ones.As another evidence of the generality of our framework, we show that the classic caching/paging problem for static objects can be reduced to a stream join problem and analyzed under our framework, yielding results that agree with or extend classic ones.
Maximum Likelihood Sound Source Localization and Beamforming for Directional Microphone Arrays in Distributed Meetings (2008)

In distributed meeting applications, microphone arrays have been widely used to capture superior speech sound and perform speaker localization through sound source localization (SSL) and beamforming. This paper presents a unified maximum likelihood framework of these two techniques, and demonstrates how such a framework can be adapted to create efficient SSL and beamforming algorithms for reverberant rooms and unknown directional patterns of microphones. The proposed method is closely related to steered response power-based algorithms, which are known to work extremely well in real-world environments. We demonstrate the effectiveness of the proposed method on challenging synthetic and real-world datasets, including over six hours of recorded meetings.
Coloring heuristics for register allocation (1989)

We describe an improvement to a heuristic introduced by Chaitin for use in graph coloring register allocation. Our modified heuristic produces better colorings, with less spill code. It has similar compile-time and implementation requirements. We present experimental data to compare the two methods.
Concanavalin A-induced B-cell proliferation mediated by allogeneically derived helper factors. (1986)

Highly purified, small, resting murine Ig-positive spleen cells could be induced to proliferate by concanavalin A (Con A) if the activation was supported by allogeneic helper factors (AHF). Con A or AHF alone was unable to induce cell proliferation as determined by incorporation of [methyl-3H] thymidine. However, if AHF produced by a mixed lymphocyte culture was present together with Con A, the B lymphocytes were strongly activated exhibiting a stimulation index of approximately 2000 as compared to Con A alone. The dose-response maximum was obtained after a 4-day culture using 25% of a supernatant from a mixed lymphocyte culture as a source of AHF. The kinetics of the AHF-supported B-cell activation was also investigated. The activation could be completely inhibited by the addition of 100 mM methyl alpha-D-mannopyranoside at the initiation of the culture, but, if added 14-18 hr later, the cells have had the necessary induction period and a proliferation could be recorded. AHF had to be present at the initiation of the cultures, otherwise the response immediately diminished, whereas Con A could be added up to 6 hr after initiation without affecting the proliferative response.
P‐111: The Mechanical‐Optical Properties of Wire‐Grid Type Polarizer in Projection Display System (2002)

Abstract In order to eliminate the thermal issues of the polymer based polarizer and thermal induce birefringence of bulky PBS, the wire‐grid type polarizer is a promising optical component. However, as a part of the imaging optics, mechanical holding may affect the image qualities. In this article, two configurations for using wire‐grid polarization are introduced. The image defects including astigmatism and distortion due to improper mechanical holding are evaluated.
Preclinical biology of alpha interferons. (1986)

The availability of large quantities of purified recombinant human alpha interferons has permitted an expansion of studies on the preclinical biology of interferon. These purified preparations have definitively established that interferon exhibits pleiotypic effects on cellular function, including antiviral, antiproliferative, and immunomodulatory activities. Thus, interferon can exert therapeutic activity by both direct effects on the growth of the tumor and by modulation of the biologic response of the host. The exact mechanism of action will most probably vary from patient to patient. The variety of biologic activities that interferon displays, as well as the fact that it is highly species-specific, makes it difficult to design preclinical studies that can provide guidance for the clinical application of interferon as an antineoplastic agent. Two models that have provided useful preclinical data on human cell lines or fresh biopsies are reviewed: the human tumor clonogenic assay and human tumor xenografts in immunodeficient mice. These models indicate that interferon is likely to be an effective treatment for a broad range of malignancies, and that the response will be highly dependent on the type of interferon as well as its dose, schedule, and route of administration. Both models have provided evidence that alpha interferon may demonstrate a synergistic or additive interaction with standard chemotherapeutic agents like cyclophosphamide or doxorubicin. The utility of any preclinical model for predicting an individual patient's response to interferon is yet to be established.
ChemInform Abstract: An Improved Synthesis of Muscimol. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
GPUs and the Future of Parallel Computing (2011)

This article discusses the capabilities of state-of-the art GPU-based high-throughput computing systems and considers the challenges to scaling single-chip parallel-computing systems, highlighting high-impact areas that the computing research community can address. Nvidia Research is investigating an architecture for a heterogeneous high-performance computing system that seeks to address these challenges.
Ketogenic diets, mitochondria, and neurological diseases (2014)

The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate "classic KD", as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD.
A simple artificial urine for the growth of urinary pathogens (1997)

A simple artificial urine medium (AUM) has been developed which provides conditions similar to that found in human urine. AUM solidified with agar enabled the recovery of a wide range of urease-positive and -negative urinary pathogens. Liquid AUM supported growth at concentrations of up to 10(8) cfu ml-1, as found in normal urine. Reproducible, steady-state growth also occurred over many generations in continuous culture. AUM was capable of forming crystals and encrustations resembling those found in natural urinary tract infections. The medium is a suitable replacement for normal urine for use in a wide range of experiments modelling the growth and attachment of urinary pathogens in the clinical environment.
Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes (1991)

The JE gene was first described as a platelet-derived growth factor (PDGF)-inducible gene in mouse 3T3 cells. The human homologue of JE encodes a protein whose predicted amino acid sequence is identical to that of the monocyte chemoattractant MCP-1 (also called MCAF and SMC-CF), which belongs to a recently identified family of small secretory proteins with cytokine properties. We purified recombinant human MCP-1/JE (hMCP-1/JE) produced in COS cells and demonstrated that it is chemotactic for human monocytes with a specific activity similar to natural MCP-1. In addition, pure recombinant hMCP-1/JE stimulates monocytes, inducing an increase in cytosolic free calcium and the respiratory burst, but is completely inactive on human neutrophils. These results help to define functionally a well-known growth factor-inducible gene and a member of a new family of cytokines.
Global spread of antibiotic resistance: the example of New Delhi metallo-β-lactamase (NDM)-mediated carbapenem resistance (2013)

The rapidity with which new types of antibiotic resistance can disseminate globally following their initial emergence or recognition is exemplified by the novel carbapenemase New Delhi metallo-β-lactamase (NDM). The first documented case of infection caused by bacteria producing NDM occurred in 2008, although retrospective analyses of stored cultures have identified the gene encoding this enzyme (blaNDM) in Enterobacteriaceae isolated in 2006. Since its first description, NDM carbapenemase has been reported from 40 countries worldwide, encompassing all continents except South America and Antarctica. The spread of NDM has a complex epidemiology involving the spread of a variety of species of NDM-positive bacteria and the inter-strain, inter-species and inter-genus transmission of diverse plasmids containing blaNDM, with the latter mechanism having played a more prominent role to date. The spread of NDM illustrates that antibiotic resistance is a public health problem that transcends national borders and will require international cooperation between health authorities if it is to be controlled.
Optical methods for distance and displacement measurements (2012)

This tutorial reviews various noncontact optical sensing techniques that can be used to measure distances to objects, and related parameters such as displacements, surface profiles, velocities and vibrations. The techniques that are discussed and compared include intensity-based sensing, triangulation, time-of-flight sensing, confocal sensing, Doppler sensing, and various kinds of interferometric sensing with both high- and low-coherence sources.
Analysis of convolutional encoders and synthesis of rate-2/n Viterbi decoders (1996)

In this correspondence, the problem of obtaining efficient hardware for Viterbi decoders for high-rate convolutional encoders is addressed. It is first shown that the graphs describing the interconnection of the add-compare-select units required may be classified in terms of structures of which there are only a small number for a given code constraint length. They correspond to the assignment of individual register lengths in the ensemble of shift registers in the feedforward encoder. The structures relate to the partitioning of the states such that common successors are grouped together and successive partitioning leads to a hierarchical, modular VLSI layout method. Example symbolic grid layouts are given for 16- and 64-state codes. It is noted that within a given structure, the parity check matrices map into local wiring patterns implying a method for implementing class-universal programmable or adaptive decoders.
Acceleration of the recognition rate between grafted ligands and receptors with magnetic forces (2006)

When ligands and receptors are both attached on surfaces, because of the restriction of configurational freedom, their recognition kinetics may be substantially reduced as compared with freely diffusing species. In nature, this reduction may influence the efficiency of the capture and adhesion of circulating cells. Here we show that similar consequences are observed for colloids grafted with biomolecules that are used as probes for diagnostics. We exploit Brownian magnetic colloids that self-assemble into linear chains to show also that the resulting one-dimensional confinement considerably accelerates the recognition rate between grafted receptors and their ligands. We propose that because confinement significantly augments the colliding frequency, it also causes a large increase in the attempt frequency of the recognition. This work gives the basis of a rapid, homogeneous, and highly sensitive bioanalysis method.
On the capacity of BICM with QAM constellations (2009)

In this tutorial paper we analyze the capacity of bit-interleaved coded modulation (BICM) with quadrature amplitude modulation (QAM) constellations, and we pay special attention to different bit-to-symbol labeling strategies. The relation between the BICM capacity and the capacity of other CM schemes such as trellis coded modulation (TCM) and multilevel codes (MLC) is analyzed. Motivated by the fact that for BICM with some particular labelings, the same Eb/No maps to more than one BICM capacity value, we study the relation between the capacity and Eb/No. In particular, we present some analytical results on this relation, and we also give an intuitive explanation for the somehow contradictory behavior of these curves.
Current Perspectives on Statins (2000)

Statins (HMG-CoA reductase inhibitors) are used widely for the treatment of hypercholesterolemia. They inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Statins are well tolerated and have an excellent safety record. Clinical trials in patients with and without coronary heart disease and with and without high cholesterol have demonstrated consistently that statins reduce the relative risk of major coronary events by approximately 30% and produce a greater absolute benefit in patients with higher baseline risk. Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis, and inflammation. Mechanisms independent of LDL lowering may play an important role in the clinical benefits conferred by these drugs and may ultimately broaden their indication from lipid-lowering to antiatherogenic agents.
Measurement of ligand-induced activation in single viable T cells using the lacZ reporter gene. (1991)

We have used the bacterial beta-galactosidase gene (lacZ) as a reporter gene for the rapid measurement of T-cell antigen receptor (TCR)-mediated activation of individual T cells. The reporter construct contained the lacZ gene under the control of the nuclear factor of activated T cells (NF-AT) element of the human interleukin 2 enhancer [Fiering, S., Northrop, J. P., Nolan, G. P., Matilla, P., Crabtree, G. R. & Herzenberg, L. A. (1990) Genes Dev. 4, 1823-1834]. The activity of the intracellular lacZ enzyme was analyzed by flow cytometric measurement of fluorescein accumulation in cells loaded with the fluorogenic beta-galactosidase substrate fluorescein di-beta-D-galactopyranoside. As a model system, the T-cell hybridoma BO4H9.1, which is specific for the lysozyme peptide (amino acids 74-88)/Ab complex, was transfected with the NF-AT-lacZ construct. lacZ activity was induced in 50-100% of the transfectant cells following exposure to pharmacological agents, to the physiological peptide/major histocompatibility complex ligand, or to other TCR-specific stimuli. Interestingly, increasing concentrations of the stimulus increased the fraction of lacZ+ cells, but not the level of lacZ activity per cell. Even under widely varying levels of stimulus, the level of lacZ activity in individual lacZ+ cells remained within a remarkably narrow range. These results demonstrate that TCR-mediated activation can be readily measured in single T cells and strongly suggest that, once committed to activation, the level of NF-AT transcriptional activity in individual T cells is independent of the form or concentration of stimulus. This assay is likely to prove useful for the study of early activation events in individual T cells and of TCR ligands.
Expression of the Major Envelope Glycoprotein gp350/220 of Epstein-Barr Virus by a Recombinant Varicella Zoster Virus (1987)

Epstein-Barr virus (EBV) is a lymphotropic gamma herpesvirus that is the causative agent of infectious mononucleosis. In addition, it is etiologically associated with Burkitt’s lymphoma and nasopharyngeal carcinoma which affect a significant percentage of the world population, most notably in Africa and Asia. Subunit vaccines against EBV have been proposed; however a live attenuated vaccine would have a number of advantages over this approach. Due to the biology of EBV it would be difficult to attenuate the virus for use as a vaccine. The use of live viruses as vectors for immunization against heterologous pathogens has generated much interest over the past several years (1) and could be used when no attenuated strain is available. This approach also has several advantages over subunit-derived vaccines. It allows for post-translational modifications of an antigen and antigen presentation more closely resembling those occurring during the course of a natural infection, as well as amplification of the heterologous antigen being expressed.
Exogenous alkaline phosphatase for the treatment of patients with moderate to severe ulcerative colitis (2009)

In this uncontrolled trial, administration of exogenous AP enzyme daily over a 7-day course to patients with UC was associated with short-term improvement in disease activity scores, with clinical effects being observed within 21 days and associated with reductions in C-reactive protein and stool calprotectin. AP enzyme treatment was well tolerated and nonimmunogenic.
A rendezvous with the queen of ion channels: Three decades of ion channel research by David T Yue and his Calcium Signals Laboratory (2015)

David T. Yue was a renowned biophysicist who dedicated his life to the study of Ca(2+) signaling in cells. In the wake of his passing, we are left not only with a feeling of great loss, but with a tremendous and impactful body of work contributed by a remarkable man. David's research spanned the spectrum from atomic structure to organ systems, with a quantitative rigor aimed at understanding the fundamental mechanisms underlying biological function. Along the way he developed new tools and approaches, enabling not only his own research but that of his contemporaries and those who will come after him. While we cannot hope to replicate the eloquence and style we are accustomed to in David's writing, we nonetheless undertake a review of David's chosen field of study with a focus on many of his contributions to the calcium channel field.
RET proto‐oncogene mutations are restricted to codons 634 and 918 in mainland Chinese families with MEN2A and MEN2B (2007)

RET proto-oncogene mutations were restricted to codon 634 and 918 in Chinese families with MEN2A and MEN2B. In general the genetic characteristics of these patients with MEN2A and MEN2B reflect the general pattern around the world and it remains to be determined with larger studies in China whether Chinese patients have a different genetic pattern of mutations.