gebhart/patrepeval huggingface dataset:
Osimertinib (AZD9291) Enhanced the Efficacy of Chemotherapeutic Agents in ABCB1- and ABCG2-Overexpressing Cells In Vitro, In Vivo , and Ex Vivo (2016)

The overexpression of ATP-binding cassette (ABC) transporters has been proved to be a major trigger for multidrug resistance (MDR) in certain types of cancer. In our study, we investigated whether osimertinib (AZD9291), a third-generation irreversible tyrosine kinase inhibitor of both activating EGFR mutations and resistance-associated T790M point mutation, could reverse MDR induced by ABCB1 and ABCG2 in vitro, in vivo, and ex vivo Our results showed that osimertinib significantly increased the sensitivity of ABCB1- and ABCG2-overexpressing cells to their substrate chemotherapeutic agents in vitro and in the model of ABCB1-overexpressing KBv200 cell xenograft in nude mice. Mechanistically, osimertinib increased the intracellular accumulations of doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, osimertinib stimulated the ATPase activity of both ABCB1 and ABCG2 and competed with the [(125)I] iodoarylazidoprazosin photolabeling bound to ABCB1 or ABCG2, but did not alter the localization and expression of ABCB1 or ABCG2 in mRNA and protein levels nor the phosphorylations of EGFR, AKT, and ERK. Importantly, osimertinib also enhanced the cytotoxicity of DOX and intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. Overall, these findings suggest osimertinib reverses ABCB1- and ABCG2-mediated MDR via inhibiting ABCB1 and ABCG2 from pumping out chemotherapeutic agents and provide possibility for cancer combinational therapy with osimertinib in the clinic. Mol Cancer Ther; 15(8); 1845-58. ©2016 AACR.
Large-scale visual sentiment ontology and detectors using adjective noun pairs (2013)

We address the challenge of sentiment analysis from visual content. In contrast to existing methods which infer sentiment or emotion directly from visual low-level features, we propose a novel approach based on understanding of the visual concepts that are strongly related to sentiments. Our key contribution is two-fold: first, we present a method built upon psychological theories and web mining to automatically construct a large-scale Visual Sentiment Ontology (VSO) consisting of more than 3,000 Adjective Noun Pairs (ANP). Second, we propose SentiBank, a novel visual concept detector library that can be used to detect the presence of 1,200 ANPs in an image. The VSO and SentiBank are distinct from existing work and will open a gate towards various applications enabled by automatic sentiment analysis. Experiments on detecting sentiment of image tweets demonstrate significant improvement in detection accuracy when comparing the proposed SentiBank based predictors with the text-based approaches. The effort also leads to a large publicly available resource consisting of a visual sentiment ontology, a large detector library, and the training/testing benchmark for visual sentiment analysis.
The Voltage Sensor in Voltage-Dependent Ion Channels (2000)

In voltage-dependent Na, K, or Ca channels, the probability of opening is modified by the membrane potential. This is achieved through a voltage sensor that detects the voltage and transfers its energy to the pore to control its gate. We present here the theoretical basis of the energy coupling between the electric field and the voltage, which allows the interpretation of the gating charge that moves in one channel. Movement of the gating charge constitutes the gating current. The properties are described, along with macroscopic data and gating current noise analysis, in relation to the operation of the voltage sensor and the opening of the channel. Structural details of the voltage sensor operation were resolved initially by locating the residues that make up the voltage sensor using mutagenesis experiments and determining the number of charges per channel. The changes in conformation are then analyzed based on the differential exposure of cysteine or histidine-substituted residues. Site-directed fluorescence labeling is then analyzed as another powerful indicator of conformational changes that allows time and voltage correlation of local changes seen by the fluorophores with the global change seen by the electrophysiology of gating currents and ionic currents. Finally, we describe the novel results on lanthanide-based resonance energy transfer that show small distance changes between residues in the channel molecule. All of the electrophysiological and the structural information are finally summarized in a physical model of a voltage-dependent channel in which a change in membrane potential causes rotation of the S4 segment that changes the exposure of the basic residues from an internally connected aqueous crevice at hyperpolarized potentials to an externally connected aqueous crevice at depolarized potentials.
The Antigenic Structure of Proteins: A Reappraisal (1984)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy (1986)

Pathological, morphometric, and teased fiber studies of sural nerve from 36 diabetic patients with (n = 32) and without (n = 4) neuropathy and from 47 healthy subjects provide evidence that in diabetic polyneuropathy: (1) fiber loss is primary; (2) demyelination and remyelination with or without onion bulb formation are secondary; (3) remaining fibers, on average, have the same ratio of small to large fibers as in healthy individuals, but with a greatly increased variability; and (4) the spatial distribution of fiber loss is both diffuse and multifocal. Criteria developed during the study of experimental models of ischemic neuropathy were employed to assess whether ischemic nerve damage had occurred in diabetic polyneuropathy. We conclude that there is increasing evidence that microvascular pathological abnormality and ischemia may be involved in the pathogenesis of human diabetic polyneuropathy. Cases with selective loss of small or large afferent fibers are probably extremes of a normal distribution and not different disorders.
ISOLATION AND GENETIC ANALYSIS OF MUTANT STRAINS OF CHLAMYDOMONAS REINHARDI DEFECTIVE IN GAMETIC DIFFERENTIATION (1976)

Impotent mutant strains of Chlamydomonas reinhardi, mating-type (mt) plus, are described that have normal growth and motility but fail to differentiate into normal gametes. Procedures for their isolation and their genetic analysis are described. Five of the imp strains (imp-2, imp-5, imp-l, imp-7, and imp-8) exhibit no flagellar agglutination when mixed with mt- or mt+ gametes and the mutations are shown to be unlinked to the mt locus (with the possible exception of imp-7). Two of the strains (imp-3 and imp-4) carry leaky mutations that affect cell fusion; neither mutation is found by tetrad analysis to be linked to mt or to the other. Cells of the imp-1 strain agglutinate well with mt- gametes and active agglutination continues for up to 48 hours, but cell fusion occurs only very rarely. Analysis of these rare zygotes indicates that imp-1 is closely linked to the mt+ locus, and fine-structural studies reveal that imp-1 gametes produce a mutant mating structure involved in zygotic cell fusion. The development of sexuality in C. reinhardi therefore appears amenable to genetic dissection.
Coherence Examination of Nonlinearly Broadened Phase-Modulated CW Laser Frequency Combs using a DPSK Encoder/Decoder (2007)

Optical coherence of 9.953 GHz nonlinearly broadened phase-modulated CW laser combs using normal and anomalous dispersive media are experimentally characterized using a DPSK encoder/decoder. Normal-dispersion-broadened combs show good DPSK compatibility.
Is sustained Production of Tumor Necrosis Factor-α Relevant to the Development of Pustular Psoriasis? (1993)

Tumor necrosis factor-alpha (TNF-alpha) has been implicated as one of the critical mediators of psoriasis. Evidence for an important role on the progression of the disease is increasing, while recent clinical studies have suggested its beneficial role in the disease. Based on the results of our sequential analysis of the serum cytokine levels in a patient with pustular psoriasis, we speculate that immunologic effects of constitutive local release of TNF-alpha may be quite different from those of its systemic injection.
Suppression of radiation‐induced neoplastic transformation by overexpression of mitochondrial superoxide dismutase (1992)

Manganese superoxide dismutase (MnSOD) scavenges toxic superoxide radicals produced in the mitochondria. Transfection of the human MnSOD gene into mouse C3H 10T1/2 cells resulted in production of active MnSOD, which was properly transported into mitochondria. Overexpression of MnSOD protected cells from radiation-, but not chemically-induced neoplastic transformation. This finding demonstrates that oxidative stress that occurs in the mitochondria plays an important role in the development of neoplastic transformation.
Codes for DNA storage channels (2015)

We consider the problem of assembling a sequence based on a collection of its substrings observed through a noisy channel. This problem of reconstructing sequences from traces was first investigated in the noiseless setting under the name of “Markov type” analysis. Here, we explain the connection between the problem and the problem of DNA synthesis and sequencing, and introduce the notion of a DNA storage channel. We analyze the number of sequence equivalence classes under the channel mapping and propose new asymmetric coding techniques to combat the effects of synthesis noise. In our analysis, we make use of Ehrhart theory for rational polytopes.
Visual Prostheses (2001)

The development of man-made systems to restore functional vision in the profoundly blind has recently undergone a renaissance that has been fueled by a combination of celebrity and government interest, advances in the field of bioengineering, and successes with existing neuroprosthetic systems. This chapter presents the underlying physiologic principles of artificial vision, discusses three contemporary approaches to restoring functional vision in the blind, and concludes by presenting several relevant questions to vision prostheses. While there has been significant progress in the individual components constituting an artificial vision system, the remaining challenge of integrating these components with each other and the nervous system does not lie strictly in the realm of neuroscience, medicine, or engineering but at the interface of all three. In spite of the apparent complexity of an artificial vision system, it is not unreasonable to be optimistic about its eventual success.
mei-1, a gene required for meiotic spindle formation in Caenorhabditis elegans, is a member of a family of ATPases. (1994)

Meiotic spindle formation in the female germline of Caenorhabditis elegans requires expression of the gene mei-1. We have cloned mei-1 by transformation rescue and found that it resides near a hot spot for recombination, in an area of high gene density. The highest levels of mei-1 mRNA accumulate in the female germline of adult hermaphrodites as well as in fertilized embryos. The message persists for several hours after the protein functions in embryos, implying the need for post-transcriptional regulation. Two alternatively spliced messages are made that would result in proteins that differ internally by three amino acids; the larger of the two mRNAs is preferentially enriched in the female germline. The sequence of mei-1 shows that it is a member of a newly described family of ATPases that share a highly conserved nucleotide-binding site; four dominant-negative mutations of mei-1 are found at or near this region. Divergent roles ascribed to this family include membrane function, proteolysis, transcription and cell cycle regulation.
A 15-ns 32*32-b CMOS multiplier with an improved parallel structure (1990)

A high-speed 32*32-b parallel multiplier with an improved parallel structure using 0.8- μm CMOS triple-level-metal technology is discussed. A unit adder, a 4-2 compressor, enhances the parallelism of the multiplier array. A 25% reduction in the propagation delay time is achieved by using the compressor. The multiplier contains 27704 transistors with a 2.68-*2.71-mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> die area. The multiplication time is 15 ns at 5 V with a power dissipation of 277 mW at 10-MHz operation. The triple-level-metal interconnection technology reduces the multiplier layout area. Compared with double-level-metal technology, a 27% chip size reduction is achieved.
Efficient nano iron particle-labeling and noninvasive MR imaging of mouse bone marrow-derived endothelial progenitor cells (2011)

In this study, we sought to label mouse bone marrow-derived endothelial progenitor cells (EPCs) with Resovist(®) in vitro and to image them using 7.0 Tesla (T) magnetic resonance imaging (MRI). Mouse bone marrow-derived EPCs were cultured in endothelial basal medium with endothelial growth supplement. They were then characterized by immunocytochemistry, flow cytometry, and fluorescence quantitative polymerase chain reaction. Their functions were evaluated by measuring their uptake of 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine-labeled acetylated low-density lipoprotein (Dil-Ac-LDL), binding of fluorine isothiocyanate (FITC)-labeled Ulex europaeus agglutinin (UEA), and formation of capillary-like networks. EPCs were labeled with superparamagnetic iron oxide (SPIO) and their proliferation was then assessed in a water-soluble tetrazolium (WST-8)-based cell proliferation assay. Spin echo sequence (multislice, multiecho [MSME]) and gradient echo sequence (2D-FLASH) were used to detect differences in the numbers of labeled cells by 7.0 T MRI. The results showed that the cultured cells were of "cobblestone"-like shape and positive for CD133, CD34, CD31, von Willebrand factor, kinase domain receptor, and CD45, but negative for F4/80. They could take up Dil-Ac-LDL, bind FITC-UEA, and form capillary-like networks on Matrigel in vitro. Prussian-blue staining demonstrated that the cells were efficiently labeled with SPIO. The single-cell T2* effect was more obvious in the 2D-FLASH sequence than in the MSME sequence. Further, there were almost no adverse effects on cell vitality and proliferation. In conclusion, mouse bone marrow-derived EPCs can be efficiently labeled with SPIO and imaged with 7.0-T MRI. They may thus be traced by MRI following transplantation for blood vessel disorders and cancer treatment.
Performance issues in mobile wireless networks (1996)

The research presented in this dissertation deals with the following performance issues in mobile wireless networks: recovery, location management and routing. The mobile wireless environment poses challenging fault-tolerant data management problems due to the mobility of the users, limited bandwidth on the wireless link, and power restrictions on the mobile hosts. Thus, traditional fault-tolerance schemes cannot be directly applied to these systems. To this effect, extensions to existing traditional recovery schemes are presented which suit this environment. Analytical models are built to analyze the performance of these schemes to determine those environments where a particular recovery scheme is best suited. The trade-off parameters to evaluate the r...
Generation of free radicals by increasing the temperature after γ-irradiation of polyethylene (1984)

Abstract The total radical decay in γ-irradiated polyethylene, measured by EPR, is discussed. By using the model of broad distribution of reaction constants and by an improvement of the estimate of radical concentrations, it is proved that radical-generating reactions occur during the temperature increase after γ-irradiation. The number of total radicals produced that are generated during the temperature increase is of the same order of magnitude as the radicals initially produced by the γ-irradiation. Some arguments are summarized to support the applicability of the model of broad distribution.
Recent advances in the synthesis of well‐defined glycopolymers (2007)

Abstract Glycopolymers are receiving increasing interest due to their application in areas, such as glycomics, medicine, biotechnology, sensors, and separation science. Consequently, new methods for their synthesis are constantly being developed, with an increasing emphasis on the preparation of well‐defined polymers and on the production of complex macromolecular architectures such as stars. This review covers recent developments in the synthesis of glycopolymers, with a particular emphasis on (i) the use of controlled radical polymerization to prepare well‐defined glycopolymers from unprotected monomers and (ii) postpolymerization modification strategies using reactive polymer precursors (including “click” reactions). Recent work on the production of glycosylated polypeptides, which are under investigation as mimics of naturally occurring glycoproteins, is also included. The authors offer some suggestions as to future developments and remaining challenges in this topical area of polymer chemistry. © 2007 Wiley Periodicals, Inc. J Polym Sci PartA: Polym Chem45: 2059–2072, 2007
Metal-catalysed tandem metathesis-hydrogenation reactions for the synthesis of carba analogues of cyclic peptides (2005)

Dicarba cyclic peptide analogues of the cystine-containing octapeptides octreotide, lanreotide, and vapreotide, all known somatostatin analogues, have been synthesized via an on-resin homogeneous metal-catalysed sequence involving ruthenium-catalysed ring-closing metathesis followed by rhodium-catalysed hydrogenation.Key words: dicarba-analogues of cystine-containing peptides, octreotide, vapreotide, and lanreotide; tandem ring-closing metathesis and hydrogenation.
Lymphocyte Gene Therapy (1991)

Genetically corrected T cells are currently under investigation as a treatment for severe combined immunodeficiency disease resulting from a lack of adenosine deaminase (ADA). Monthly injections of these ADA-corrected T cells have resulted in measurable ADA activity in the peripheral blood and the in vivo production of antibody to blood group antigen. Genetically corrected T cells appear to be clinically valuable vehicles for gene therapy.
Quantitative, Label-Free Detection of Five Protein Biomarkers Using Multiplexed Arrays of Silicon Photonic Microring Resonators (2009)

Because of the inherent complexity of biochemical pathways commonly altered in disease states, it has become accepted that multiplexed analyses can provide a more informative biomolecular understanding of disease onset and progression. Importantly, compared to conventional single-parameter assays, the detailed biomolecular insight gleaned from multiparameter measurements has the potential to greatly improve disease diagnostics, prognostics, and theragnostics. We have previously reported the utility of silicon photonic microring resonators for the sensitive quantitation of a single disease biomarker and herein demonstrate the first example of optical microcavity resonator arrays performing quantitative, label-free, multiplexed analyses of clinically relevant protein biomarkers. In this report, the concentrations of prostate specific antigen (PSA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8) are simultaneously determined in three unknown protein cocktail solutions. This letter demonstrates that multiple immunoassays can be performed concurrently on a microresonator platform without any accompanying loss of sensitivity or measurement precision, and therefore, this report lays the groundwork for future applications involving multiplexed analysis of clinically relevant samples.
Development of a noninvasive corneal birefringence-compensated glucose-sensing polarimeter (2003)

In the recent past, optical polarimetry has been shown as a potential method for noninvasive physiologic glucose sensing in the eye. Although the necessary sensitivity and accuracy have been demonstrated experimentally through in vitro studies using a range of media from simplistic glucose doped-water to more complex media such as aqueous humor, the main problem currently hindering long-term in vivo measurements is corneal birefringence coupled with motion artifact. This is due to the inability to distinguish E-field rotation due to glucose from the effects of time varying corneal birefringence. In this investigation, the effect of corneal birefringence will be discussed and a potential method to overcome this problem will be presented with supporting results.
Low-Density Self-Assembled Monolayers on Gold Derived from Chelating 2-Monoalkylpropane-1,3-dithiols (1999)

Low-density self-assembled monolayers (SAMs) on gold were generated by the adsorption of a series of specifically designed 2-monoalkylpropane-1,3-dithiol derivatives, CH3(CH2)nCH[CH2SH]2, where n = 11, 13, 14. The monolayers were characterized by optical ellipsometry, X-ray photoelectron spectroscopy, contact angle goniometry, polarization modulation infrared reflection absorption spectroscopy, and sum-frequency generation. Comparison of these data to those collected on SAMs generated from normal alkanethiols, CH3(CH2)n+2SH, and 2,2-dialkylpropane-1,3-dithiol derivatives, [CH3(CH2)n]2C[CH2SH]2, of similar chain length suggests that the new “monoalkanedithiol” SAMs are the least crystalline, exposing both methyl and methylene groups at the interface due to the low density of alkyl chains. Further comparison of these low-density SAMs to those obtained on branched and linear polyethylene films suggests that the exposure of interfacial methylene groups is greater for the polymer films.
Membranes and filtration: Membrane filtration in the biopharm industry (2008)

Mandar Dixit of Sartorius Stedim explains the usage and importance of membranes as a sterile form of filter media in the biopharmaceutical industries, with an overview of the general process and a look at recent developments in this sector of the filtration industry.
A comparative study of artificial intelligence and human doctors for the purpose of triage and diagnosis (2018)

Online symptom checkers have significant potential to improve patient care, however their reliability and accuracy remain variable. We hypothesised that an artificial intelligence (AI) powered triage and diagnostic system would compare favourably with human doctors with respect to triage and diagnostic accuracy. We performed a prospective validation study of the accuracy and safety of an AI powered triage and diagnostic system. Identical cases were evaluated by both an AI system and human doctors. Differential diagnoses and triage outcomes were evaluated by an independent judge, who was blinded from knowing the source (AI system or human doctor) of the outcomes. Independently of these cases, vignettes from publicly available resources were also assessed to provide a benchmark to previous studies and the diagnostic component of the MRCGP exam. Overall we found that the Babylon AI powered Triage and Diagnostic System was able to identify the condition modelled by a clinical vignette with accuracy comparable to human doctors (in terms of precision and recall). In addition, we found that the triage advice recommended by the AI System was, on average, safer than that of human doctors, when compared to the ranges of acceptable triage provided by independent expert judges, with only a minimal reduction in appropriateness.