gebhart/patrepeval huggingface dataset:
Engineering CAR-T cells (2017)

Chimeric antigen receptor redirected T cells (CAR-T cells) have achieved inspiring outcomes in patients with B cell malignancies, and are now being investigated in other hematologic malignancies and solid tumors. CAR-T cells are generated by the T cells from patients' or donors' blood. After the T cells are expanded and genetically modified, they are reinfused into the patients. However, many challenges still need to be resolved in order for this technology to gain widespread adoption. In this review, we first discuss the structure and evolution of chimeric antigen receptors. We then report on the tools used for production of CAR-T cells. Finally, we address the challenges posed by CAR-T cells.
Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. (1991)

Bafilomycin A1 is known as a strong inhibitor of the vacuolar type H(+)-ATPase in vitro, whereas other type ATPases, e.g. F1,F0-ATPase, are not affected by this antibiotic (Bowman, E.M., Siebers, A., and Altendorf, K. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7972-7976). Effects of this inhibitor on lysosomes of living cultured cells were tested. The acidification of lysosomes revealed by the incubation with acridine orange was completely inhibited when BNL CL.2 and A431 cells were treated with 0.1-1 microM bafilomycin A1. The effect was revealed by washing the cells. Both studies using 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine and fluorescein isothiocyanate-dextran showed that the intralysomal pH of A431 cells increased from about 5.1-5.5 to about 6.3 in the presence of 1 microM bafilomycin A1. The pH increased gradually in about 50 min. In the presence of 1 microM bafilomycin A1, 125I-labeled epidermal growth factor (EGF) bound to the cell surface at 4 degrees C was internalized normally into the cells at 37 degrees C but was not degraded at all, in marked contrast to the rapid degradation of 125I-EGF in the control cells without the drug. Immunogold electron microscopy showed that EGF was transported into lysosomes irrespective of the addition of bafilomycin A1. These results suggest that the vacuolar type H(+)-ATPase plays a pivotal role in acidification and protein degradation in the lysosomes in vivo.
Self-masked high-aspect-ratio polymer nanopillars (2008)

In this paper, a simple, cost effective, and potentially universal method is proposed for the formation of high-aspect-ratio nanopillars on various polymers. Our method involves direct reactive ion etching (RIE) using self-formed nanomasks oriented from a dummy material (cover glass). The mechanism is evaluated using nanopillar characterization and surface analysis results from x-ray photoelectron microscopy (XPS) and Auger electron microscopy (AES). By varying the dummy material configuration and modifying the RIE etching time, the distribution and dimensions of the nanopillars can be manipulated to meet a range of requirements. The maximum structural aspect ratio of 60 (6.7 microm high and 112 nm thick nanopillars) can be easily prepared using a 60 min self-masked high-aspect-ratio polymer nanopillars fabrication (SMHAR) process on poly(monochloro-p-xylylene) (Parylene C). Furthermore, nanopillars can also be generated using the same SMHAR process on poly(dimethylsiloxane) (PDMS) and SU-8 photoresist, creating nanostructured PDMS or SU-8 materials in lab-on-a-chip (LOC) or nano/micro-electromechanical systems (N/MEMS).
Specific Signals Generated by the Cytoplasmic Domain of the Granulocyte Colony-Stimulating Factor (G-CSF) Receptor Are Not Required for G-CSF–Dependent Granulocytic Differentiation (1998)

Granulocyte colony-stimulating factor (G-CSF) is the principal growth factor regulating the production of neutrophils, yet its role in lineage commitment and terminal differentiation of hematopoietic progenitor cells is controversial. In this study, we describe a system to study the role of G-CSF receptor (G-CSFR) signals in granulocytic differentiation using retroviral transduction of G-CSFR–deficient, primary hematopoietic progenitor cells. We show that ectopic expression of wild-type G-CSFR in hematopoietic progenitor cells supports G-CSF–dependent differentiation of these cells into mature granulocytes, macrophages, megakaryocytes, and erythroid cells. Furthermore, we show that two mutant G-CSFR proteins, a truncation mutant that deletes the carboxy-terminal 96 amino acids and a chimeric receptor containing the extracellular and transmembrane domains of the G-CSFR fused to the cytoplasmic domain of the erythropoietin receptor, are able to support the production of morphologically mature, chloroacetate esterase-positive, Gr-1/Mac-1–positive neutrophils in response to G-CSF. These results demonstrate that ectopic expression of the G-CSFR in hematopoietic progenitor cells allows for multilineage differentiation and suggest that unique signals generated by the cytoplasmic domain of the G-CSFR are not required for G-CSF–dependent granulocytic differentiation.
Real-time task reconfiguration support applied to an UAV-based surveillance system (2008)

Modern surveillance systems, such as those based on the use of unmanned aerial vehicles, required powerful high-performance platforms to deal with many different algorithms that make use of massive calculations. At the same time, low-cost and high-performance specific hardware (e.g., GPU, PPU) are rising and the CPUs turned to multiple cores, characterizing together an interesting and powerful heterogeneous execution platform. Therefore, reconfigurable computing is a potential paradigm for those scenarios as it can provide flexibility to explore the computational resources on heterogeneous cluster attached to a high-performance computer system platform. As the first step towards a run-time reconfigurable workload balancing framework targeting that kind of platform, application time requirements and its crosscutting behavior play an important role for task allocation decisions. This paper presents a strategy to reallocate specific tasks in a surveillance system composed by a fleet of unmanned aerial vehicles using aspect-oriented paradigms in order to address non-functional application timing constraints in the design phase. An aspect support from a framework called DERAF is used to support reconfiguration requirements and provide the resource information needed by the reconfigurable load-balancing strategy. Finally, for the case study, a special attention on radar image processing will be given.
Assessing the Reliability Worth for a Reliability-Based Optical Network Design (2002)

This paper demonstrates the assessment of the reliability worth of a network design or improvement for use in a full feasibility economic analysis. This provides a means to tradeoff between network reliability cost and worth
A Novel Learning Method for Hidden Markov Models in Speech and Audio Processing (2006)

In recent years, various discriminative learning techniques for HMMs have consistently yielded significant benefits in speech recognition. In this paper, we present a novel optimization technique using the minimum classification error (MCE) criterion to optimize the HMM parameters. Unlike maximum mutual information training where an extended Baum-Welch (EBW) algorithm exists to optimize its objective function, for MCE training the original EBW algorithm cannot be directly applied. In this work, we extend the original EBW algorithm and derive a novel method for MCE-based model parameter estimation. Compared with conventional gradient descent methods for MCE learning, the proposed method gives a solid theoretical basis, stable convergence, and it is well suited for the large-scale batch-mode training process essential in large-scale speech recognition and other pattern recognition applications. Evaluation experiments, including model training and speech recognition, are reported on both a small vocabulary task (TI-digits) and a large vocabulary task (WSJ), where the effectiveness of the proposed method is demonstrated. We expect new future applications and success of this novel learning method in general pattern recognition and multimedia processing, in addition to speech and audio processing applications we present in this paper
Syntax-guided synthesis (2013)

Abstract—The classical formulation of the program-synthesis problem is to find a program that meets a correctness specification given as a logical formula. Recent work on program synthesis and program optimization illustrates many potential benefits of allowing the user to supplement the logical specification with a syntactic template that constrains the space of allowed implementations. Our goal is to identify the core computational problem common to these proposals in a logical framework. The input to the syntax-guided synthesis problem (SyGuS) consists of a background theory, a semantic correctness specification for the desired program given by a logical formula, and a syntactic set of candidate implementations given by a grammar. The computational problem then is to find an implementation from the set of candidate expressions so that it satisfies the specification in the given theory. We describe three different instantiations of the counter-example-guided-inductive-synthesis (CEGIS) strategy for solving the synthesis problem, report on prototype implementations, and present experimental results on an initial set of benchmarks. I.
An Empirical Examination of the Antecedents of Film Tourism Experience: A Structural Model Approach (2014)

This study aims to empirically examine the antecedents of film tourism experience associated with a serialized TV drama. Drawing on film tourism and media-communication studies, a theoretical model for the causal interrelationship between production values of the TV drama, audience involvement with it, and film tourism experience at its filmed location was tested empirically using structural equation modeling (SEM) methodologies. Responses were drawn from a cross-sectional data sample of international visitors via a survey executed at Daejanggeum Theme Park in Korea. The results indicate that production values and audience involvement have a direct, positive impact on film tourism experience. Moreover, the production values have a mediating, positive impact on film tourism experience through the audience involvement construct.
Differences in gene expression during sleep and wakefulness (1999)

Compared with our understanding of the electrophysiological correlates of sleep and wakefulness, the search for correlates at the molecular level is still in its infancy. However, the evidence obtained so far supports the hypothesis that reliable molecular correlates do exist. As will be summarized in this review, levels of receptor binding, second messengers and protein phosphorylation differ between sleep and wakefulness. Moreover, compelling data obtained in different animal species suggest that the transition between sleep and wakefulness is accompanied by significant changes in gene expression. Many immediate early genes, transcription factors, plasticity-related genes and mitochondrial genes are expressed at higher levels in wakefulness than in sleep, while a few still unknown genes are up-regulated during sleep. The ongoing systematic screening of gene expression across behavioural states should prove crucial in elucidating the regulatory mechanisms of sleep homeostasis and the functions of sleep.
Epidermal growth factor receptor as a major anticancer drug target (2006)

Epidermal growth factor receptor (EGFR) is the best characterised member of the ErbB family of receptors. A lot of effort has been made to exploit the therapeutic potential of drugs acting on this receptor pathway. Monoclonal antibodies and oral tyrosine kinase inhibitors have undergone a thorough evaluation, both as single agents and in combination. However, over recent years, cancer cells have been shown to be able to harness different growth factor signalling pathways, so that single-agent therapy may not be the best way to use anti-EGFR drugs. Combinations with downstream effectors or other receptor-targeted therapies, or antiangiogenic compounds can be looked at more optimistically as effective weapons.
Acetylcholinesterase Inhibitors: Beneficial Effects on Comorbidities in Patients With Alzheimer’s Disease (2017)

Elderly patients with Alzheimer's disease (AD) and other dementias are at high risk of polypharmacy and excessive polypharmacy for common coexisting medical conditions. Polypharmacy increases the risk of drug-drug and drug-disease interactions in these patients who may not be able to communicate early symptoms of adverse drug events. Three acetylcholinesterase inhibitors (ACHEIs) have been approved for AD: donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). They are also used off-label for other causes of dementia such as Lewy body and vascular dementia. We here report evidence from the literature that ACHEI treatment, prescribed for cognitive impairment, can reduce the load of medications in patients with AD by also addressing cardiovascular, gastrointestinal, and other comorbidities. Using one drug to address multiple symptoms can reduce costs and improve medication compliance.
Alzheimer's Disease and Frontotemporal Dementia (2010)

Alzheimer's disease and frontotemporal dementia, two of the most prevalent neurodegenerative diseases, are dreaded disorders that attack the neural networks underlying memory and personality, systems
Genomic Structure of an Attenuated Quasi Species of HIV-1 from a Blood Transfusion Donor and Recipients (1995)

A blood donor infected with human immunodeficiency virus-type 1 (HIV-1) and a cohort of six blood or blood product recipients infected from this donor remain free of HIV-1-related disease with stable and normal CD4 lymphocyte counts 10 to 14 years after infection. HIV-1 sequences from either virus isolates or patient peripheral blood mononuclear cells had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR). Full-length sequencing of one isolate genome and amplification of selected HIV-1 genome regions from other cohort members revealed no other abnormalities of obvious functional significance. These data show that survival after HIV infection can be determined by the HIV genome and support the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1.
A buried-trench DRAM cell using a self-aligned epitaxy over trench technology (2003)

A novel three-dimensional buried trench (BT) memory cell, suitable for DRAM (dynamic random access memories) of 64 Mb or beyond, has been demonstrated. It uses a novel self-aligned-epitaxy-over-trench (SEOT) technology which allows the fabrication of the cell horizontal access transistor in bulk material epitaxially grown over the trench capacitor. The via connection between the access transistor and the buried trench is a vertical sublithographic contact self-aligned to the trench. This BT cell, with a minimum of 10.8 lithographic squares, was fabricated in a submicron n-well epitaxial CMOS process incorporating the SEOT technology.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Is there a role for microRNAs in exercise immunology? A synopsis of current literature and future developments. (2010)

With the discovery of microRNAs (miRNAs), an exceptional means of regulating gene expression was introduced a few years ago. MiRNAs function to inactivate specific messenger RNA transcripts leading to depletion of the corresponding protein, whereby computational studies have shown that about one third of all animal genes might be miRNA targets. Recent publications highlight the involvement of miRNAs in regulating the immune response. The aim of this review is to provide an overview of miRNA biogenesis and function, to illustrate their impact on both the innate as well as the adaptive immune system, to show the regulation of skeletal muscle plasticity and inflammation, and finally to present their possible role within the field of exercise immunology.
Efficient object detection for high resolution images (2015)

Efficient generation of high-quality object proposals is an essential step in state-of-the-art object detection systems based on deep convolutional neural networks (DCNN) features. Current object proposal algorithms are computationally inefficient in processing high resolution images containing small objects, which makes them the bottleneck in object detection systems. In this paper we present effective methods to detect objects for high resolution images. We combine two complementary strategies. The first approach is to predict bounding boxes based on adjacent visual features. The second approach uses high level image features to guide a two-step search process that adaptively focuses on regions that are likely to contain small objects. We extract features required for the two strategies by utilizing a pre-trained DCNN model known as AlexNet. We demonstrate the effectiveness of our algorithm by showing its performance on a high-resolution image subset of the SUN 2012 object detection dataset.
MicroRNA‐9 Promotion of Interleukin‐6 Expression by Inhibiting Monocyte Chemoattractant Protein–Induced Protein 1 Expression in Interleukin‐1β–Stimulated Human Chondrocytes (2015)

These findings implicate miR-9-mediated suppression of MCPIP-1 in the pathogenesis of OA via up-regulation of IL-6 expression in IL-1β-stimulated human OA chondrocytes.
Daclizumab prevents acute rejection and improves patient survival post transplantation: 1 year pooled analysis (2000)

Daclizumab is a genetically engineered human IgG1 monoclonal antibody specific for the alpha chain of the IL-2 receptor. A pooled analysis of two randomized, double-blind studies was performed on the efficacy and safety of daclizumab in renal transplantation, given in addition to standard immunosuppression. Patients receiving their first cadaveric renal allograft were randomized to receive 5 doses of daclizumab (n = 267) or placebo (n = 268), starting pre-operatively. Acute rejection at 1 year occurred less frequently with daclizumab (n = 74, 27.7 %) than with placebo (n = 116, 43.3%) (P = 0.0001). Fewer patients treated with daclizumab required anti-lymphocyte therapy for acute rejection (7.9 % vs. 15.3 %; P = 0.005). Mean cumulative doses of corticosteroids were lower with daclizumab (4133 mg) than with placebo (4562 mg). One year graft survival was 91.4 % with daclizumab, compared with 86.6 % on placebo (P = 0.065), with patient survival of 98.5 % and 95.1 % for daclizumab and placebo respectively (P = 0.022). Daclizumab was well tolerated. No increase in infectious episodes or lymphoproliferative disorders was observed with daclizumab. The incidence of cytomegalovirus infections was similar with daclizumab and placebo (15 % vs. 17.5 %). Therapy with daclizumab significantly reduces acute rejection in renal transplantation and improves patient survival without any increase in morbidity.
Nanoparticle Separations Using Miniaturized Field-flow Fractionation Systems (2005)

In this work, a µ-ElFFF system is demonstrated with complimentary on-column electrical conductivity and resonance light scattering (RLS) detection systems. The fabrication of a µ-ElFFF system is described and test results from performing separations of gold RLS Particles TM and Protein A coated/uncoated polystyrene nanospheres in the system are presented. The particles ranged in size from 40280 nm in diameter, and 0.1 µL samples, with particle concentrations as low as 1.09 x 10 -11 M, were injected into the input port of the microchannel, separated and detected. A CCD camera mounted on a microscope was used to obtain images that clearly showed the front and tail ends of the samples. The images correlated well with the response of the conductivity detector measurements. Integration of an optically based signal generation and detection method allows real-time visualization of separations and correlation of optical and electrical detector signals.
The Disulfide Folding Pathway of Human Epidermal Growth Factor (1995)

Human epidermal growth factor (EGF) contains three disulfides and 53 amino acids. Reduced/denatured EGF refolds spontaneously in vitro to acquire its native structure. The mechanism of this folding process has been elucidated by structural analysis of both acid and iodoacetate trapped intermediates. The results reveal that the folding is accompanied by a sequential flow of unfolded EGF (0-disulfide) through three groups of folding intermediates, namely 1-disulfide, 2-disulfide, and 3-disulfide (scrambled) EGF isomers, to reach the native structure. Equilibrium occurs among isomers of each class of disulfide species, and the composition of intermediates appears to be highly heterogeneous. Together, at least 27 fractions of folding intermediates have been identified, but there exist only limited numbers of well populated species which constitute more than 80% of the total intermediates found during EGF folding. Six species of such well populated intermediates have been isolated, which included two 1-S-S, two 2-S-S, and two 3-S-S scrambled species. Their disulfide structures have been identified here. Both 1-S-S isomers are found to contain non-native disulfides. One of the 2-S-S species consists of two non-native disulfides and the other admits two native disulfides. Among the six disulfides of the two scrambled species, only one is native. Together, native disulfides constitute 25% of the total disulfides found in these six well populated intermediates. These results contrast sharply to those observed with bovine pancreatic trypsin inhibitor, which has shown that well populated folding intermediates consist of exclusively native disulfides (Weissman, J. S., and Kim, P. S. (1991) Science 253, 1386-1393). We propose that well populated folding intermediates, regardless of whether they contain native or non-native disulfides, do not necessarily represent the productive species and specify the folding pathway. Furthermore, conditions influencing the efficiency of EGF folding have been investigated. It is demonstrated here that under optimized compositions of redox agents, including the use of cysteine/cystine and protein disulfide isomerase, the in vitro folding of EGF could be achieved quantitatively within 1 min.
Genetic separation of high- and low-affinity transport systems for branched-chain amino acids in Escherichia coli K-12 (1978)

The Escherichia coli K-12 mutant strain AE4107 (livH::Mu) is defective in the high-affinity binding protein-mediated uptake system for L-leucine, L-valine, and L-isoleucine (LIV-I). We have used this strain to produce mutations in the residual LIV-II membrane-bound branched-chain amino acid uptake system. Mutants selected for their inability to utilize exogenous L-leucine were found to be defective in the LIV-II system and fell into two classes. One class, represented by strain AE410709 (livP9), showed a complete loss of saturable uptake for L-leucine, L-valine, and L-isoleucine up to 50 muM, and a second class, represented by strain AE4017012 (liv-12), showed a residual component of saturable leucine uptake with increased Km. These mutations, livP9 and liv-12, were closely linked and mapped in the 74 to 78 min region of the E. coli genetic map. Strains constructed so that they lacked both LIV-I and LIV-II transport systems excreted leucine. Strains of the genotype livH+ livP were found to have normal high-affinity binding protein-mediated transport (LIV-I and leucine specific), whereas the low-affinity (LIV-II) transport was completely missing. We concluded from these studies that the high-affinity binding protein-mediated transport systems (LIV-I and leucine specific) can operate independently of the membrane-bound LIV-II system.