gebhart/patrepeval huggingface dataset:
Stroke-induced microRNAs: The potential therapeutic role for stroke (2012)

Stroke is one of the leading causes of death and disability worldwide. In past decades, researchers have studied the physiopathology and biochemistry of stroke, but knowledge of the molecular mechanisms underlying this disease remains at an early stage. To date, only recombinant tissue plasminogen activator (rtPA) has been approved by the USA FDA for acute ischemic stroke. However, as the limiting therapy time window is 4.5 h after stroke onset and patients must meet the applicable conditions, a small number of patients benefit from this therapy. Therefore, the research and development of new drugs for stroke are a big challenge for scientists. MicroRNAs (miRNAs) are short (20-23 nucleotides) single-stranded non-coding RNAs. The seed sequences at positions 2-7 from the 5' end which are partially or complementary to one or more mRNAs inhibit or degrade target mRNAs, thus playing an important role in the post-transcriptional regulation of gene expression. Disregulated miRNAs have revealed their complex role in pathophysiological processes, and have also shown their potential role in disease diagnosis, and use as drug targets in neurodegenerative diseases and cancer. Recently, studies have found aberrantly expressed miRNAs in stroke; however, the implication of deregulated miRNA expression in stroke remains largely unknown. This review briefly summarizes recent studies concerning miRNA expression in stroke in vivo and in vitro, focuses on aberrant miRNA expression, as well as discusses their potential therapeutic role for stroke.
Hierarchical Implicit Models and Likelihood-Free Variational Inference (2017)

Implicit probabilistic models are a flexible class of models defined by a simulation process for data. They form the basis for theories which encompass our understanding of the physical world. Despite this fundamental nature, the use of implicit models remains limited due to challenges in specifying complex latent structure in them, and in performing inferences in such models with large data sets. In this paper, we first introduce hierarchical implicit models (HIMs). HIMs combine the idea of implicit densities with hierarchical Bayesian modeling, thereby defining models via simulators of data with rich hidden structure. Next, we develop likelihood-free variational inference (LFVI), a scalable variational inference algorithm for HIMs. Key to LFVI is specifying a variational family that is also implicit. This matches the model's flexibility and allows for accurate approximation of the posterior. We demonstrate diverse applications: a large-scale physical simulator for predator-prey populations in ecology; a Bayesian generative adversarial network for discrete data; and a deep implicit model for text generation.
Immunodeficiency in Protein Kinase Cβ-Deficient Mice (1996)

Cross-linking of the antigen receptor on lymphocytes by antigens or antibodies to the receptor results in activation of enzymes of the protein kinase C (PKC) family. Mice homozygous for a targeted disruption of the gene encoding the PKC-betaI and PKC-betaII isoforms develop an immunodeficiency characterized by impaired humoral immune responses and reduced cellular responses of B cells, which is similar to X-linked immunodeficiency in mice. Thus PKC-betaI and PKC-betaII play an important role in B cell activation and may be functionally linked to Bruton's tyrosine kinase in antigen receptor-mediated signal transduction.
Small-molecule modulators of Hh and Wnt signaling pathways (2007)

Hedgehog (Hh) and Wnt signaling pathways play key roles in growth and patterning during embryonic development and in the postembryonic regulation of stem cell number in the epithelia. Numerous studies link aberrant modulation of these pathways to specific human diseases. This article focuses on general aspects of Hh and Wnt signal transduction and biologic molecules involved in the respective signaling cascades. Specifically, the authors summarize small-molecule modulators of both pathways that show promise as therapeutic modalities.
A forward genetic screen to explore chloroplast protein import in vivo identifies Moco sulfurase, pivotal for ABA and IAA biosynthesis and purine turnover (2010)

A genetic screen in Arabidopsis was developed to explore the regulation of chloroplast protein import in vivo using two independent reporters representing housekeeping and photosynthetic pre-proteins. We first used 5-enolpyruvylshikimate 3-phosphate synthase (EPSP synthase*), a key enzyme in the shikimic acid pathway, with a mutation that confers tolerance to the herbicide glyphosate. Because the EPSP synthase* pre-protein must be imported for its function, the loss of glyphosate tolerance provided an initial indication of an import deficiency. Second, the fate of GFP fused to a ferredoxin transit peptide (FD5-GFP) was determined. A class of altered chloroplast import (aci) mutants showed both glyphosate sensitivity and FD5-GFP mislocalized to nuclei. aci2-1 was selected for further study. Yellow fluorescent protein (YFP) fused to the transit peptide of EPSP synthase* or the small subunit of Rubisco was not imported into chloroplasts, but also localized to nuclei during protoplast transient expression. Isolated aci2-1 chloroplasts showed a 50% reduction in pre-protein import efficiency in an in vitro assay. Mutants did not grow photoautotrophically on media without sucrose and were small and dark green in soil. aci2-1 and two alleles code for Moco-sulfurase, which activates the aldehyde oxidases required for the biosynthesis of the plant hormones abscisic acid (ABA) and indole-acetic acid (IAA) and controls purine nucleotide (ATP and GTP) turnover and nitrogen recycling via xanthine dehydrogenase. These enzyme activities were not detected in aci2-1. ABA, IAA and/or purine turnover may play previously unrecognized roles in the regulation of chloroplast protein import in response to developmental, metabolic and environmental cues.
Sustained Peptide-Specific Gamma Interferon T-Cell Response in Rhesus Macaques Immunized with Human Immunodeficiency Virus gag DNA Vaccines (2002)

We examined the influence of dose and method of antigen delivery on the dynamics and durability of T-cell responses to candidate human immunodeficiency virus (HIV) vaccines. Codon-optimized sequences from the HIV gag gene were inserted into alternative DNA vaccine vectors to express the coding sequence with or without the tissue plasminogen activator leader sequence. We delivered the vaccines by intramuscular injection as plasmid DNA without adjuvant or as plasmid DNA formulated with a novel block copolymer adjuvant (CRL8623) and then monitored the ensuing T-cell responses by using a gamma interferon enzyme-linked immunospot assay. We demonstrated persistence of the cell-mediated immune (CMI) response in rhesus macaques for at least 18 months following a four-dose vaccination regimen. The plasmid vaccine, with or without CRL8623, was immunogenic in macaques; however, the form coadministered with adjuvant exhibited improved T-cell responses, with a bias toward more antigen-specific CD8(+) T cells. Finally, we examined the fine specificity of the T-cell response to the gag vaccines by testing the response of 23 vaccinated macaques to individual Gag 20-mer peptides. Collectively, the monkeys responded to 25 epitopes, and, on average, each monkey recognized a minimum of 2.7 epitopes. The results indicate that a broad and durable CMI response to HIV DNA vaccines can be induced in a relevant nonhuman primate model.
Activation of ion implanted Si in GaN using a dual AlN annealing cap (2009)

A dual annealing cap composed of a thin, low temperature metal-organic chemical vapor deposition (MOCVD) deposited AlN adhesion layer and a thicker, sputtered AlN film for added mechanical strength enabled us to anneal Si-implanted layers for 30 min at temperatures up to 1250 °C. At higher temperatures the cap was destroyed by the large partial pressure of the N2 from the GaN, which exceeds the yield strength of AlN. Electrical activations as high as 70% and electron mobilities comparable to those of in situ doped films were achieved. Compared to other methods, the surfaces are better protected using this cap because it adheres better than sputtered AlN, SiO2, or Si3N4; does not crack like MOCVD grown AlN films deposited at normal temperatures (∼1100 °C); and is stronger than thin MOCVD grown AlN films deposited at low temperatures (∼600 °C). Even though N does not escape, and in so doing, forms thermal etch pits, the surface of the annealed GaN is roughened by solid state diffusion with the surface roughness increasing with the annealing temperature.
Toward the $1000 Human Genome (2005)

Revolutionary new technologies, capable of transforming the economics of sequencing, are providing an unparalleled opportunity to analyze human genetic variation comprehensively at the whole-genome level within a realistic timeframe and at affordable costs. Current estimates suggest that it would cost somewhere in the region of 30 million US dollars to sequence an entire human genome using Sanger-based sequencing, and on one machine it would take about 60 years. Solexa is widely regarded as a company with the necessary disruptive technology to be the first to achieve the ultimate goal of the so-called 1,000 dollars human genome - the conceptual cost-point needed for routine analysis of individual genomes. Solexa's technology is based on completely novel sequencing chemistry capable of sequencing billions of individual DNA molecules simultaneously, a base at a time, to enable highly accurate, low cost analysis of an entire human genome in a single experiment. When applied over a large enough genomic region, these new approaches to resequencing will enable the simultaneous detection and typing of known, as well as unknown, polymorphisms, and will also offer information about patterns of linkage disequilibrium in the population being studied. Technological progress, leading to the advent of single-molecule-based approaches, is beginning to dramatically drive down costs and increase throughput to unprecedented levels, each being several orders of magnitude better than that which is currently available. A new sequencing paradigm based on single molecules will be faster, cheaper and more sensitive, and will permit routine analysis at the whole-genome level.
Synthesis and Properties of Star-Shaped Multiporphyrin−Phthalocyanine Light-Harvesting Arrays (1999)

Light-harvesting arrays containing four porphyrins covalently linked to a phthalocyanine in a star-shaped architecture have been synthesized. Cyclotetramerization of an ethyne-linked porphyrin−phthalonitrile in 1-pentanol in the presence of MgCl2 and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) afforded the all-magnesium porphyrin−phthalocyanine pentad in 45% yield. Similar reaction using Zn(OAc)2·2H2O afforded the all-zinc porphyrin−phthalocyanine pentad in 15% yield. Arrays with different metals (free base, Mg, Zn) in the porphyrin and phthalocyanine macrocycles have been prepared by selective demetalation and metalation steps. This approach provides rapid and convergent access to multiporphyrin−phthalocyanine arrays in diverse metalation states. The arrays are reasonably soluble in organic solvents such as toluene, THF, and CH2Cl2. The arrays exhibit strong absorption in the blue and red regions. Time-resolved and static optical measurements indicate that intramolecular singlet-excited-state energy transfer from the porphyrin to the phthalocyanine moiety is extremely rapid (picoseconds) and efficient. Ground-state electronic communication among the porphyrins is indicated by rapid hole/electron hopping among the metalloporphyrins in the arrays as detected by EPR measurements on the singly oxidized pentads. These physical measurements indicate that the porphyrin−phthalocyanine pentads possess favorable characteristics for light harvesting and other photonics applications.
High-endurance ultra-thin tunnel oxide in MONOS device structure for dynamic memory application (1995)

Ultra-thin tunnel oxide can conduct very high current through oxide via direct tunneling, and charge-to-breakdown increases dramatically due to less oxide damage. These facts point to a possibility of using thin tunnel oxide in the floating-gate device structure for dynamic memory applications. We have chosen MONOS structure in this study due to its immunity to pinhole-induced leakage and back-tunneling. The memory device exhibits fast WRITE/ERASE speed, high-endurance, long data retention and non-destructive READ. Further improvements are expected through process optimization.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Thermooptic planar polymer Bragg grating OADMs with broad tuning range (1999)

Tunable optical add/drop multiplexers (OADMs) were achieved by combining thermally tunable planar polymer Bragg gratings with optical circulators. The gratings exhibit better than 45-dB reflection with no detectable out-of-band reflection. Apodization was utilized to achieve strong sidelobe suppression, and symmetric gratings with uniform strength across the core and cladding layers were used to minimize coupling to cladding modes. These OADMs have a high-bandwidth utilization (BWU) factor of 0.92, with a minimum channel spacing of 75 GHz. They are tunable at a rate of -0.256 nm//spl deg/C. Tuning over a 20-nm range was demonstrated with a single device.
Optimization of Anti-reflection Coating for Improving the Performance of GaAs Solar Cell (2014)

The objective of this work is to reduce the front surface reflectivity of the GaAs solar cell by depositing AR-coating of appropriate thickness and refractive index material. We use MgO and ZnO film and optimize their thickness for minimum reflectivity. Results indicate that the reflectivity is reduced up to 4% for MgO film and 2% for ZnO film at solar spectrum wavelength range from 550 nm to 650 nm. The external efficiency of GaAs solar cell with AR-coating is increased by 31.53% and 33.09% for MgO and ZnO film respectively. Keywords: AM1.5D Spectrum, Anti-reflection Coating, External Efficiency, Fresnel Reflection, Interference of Light
Toll-like receptor agonist therapy can profoundly augment the antitumor activity of adoptively transferred CD8+ T cells without host preconditioning (2016)

Collectively, our results identify how and when to administer TLR agonists to augment T cell-based immunotherapy in the absence or presence of host preconditioning for treatment of advanced malignancies. Our findings have clinical implications for the design of next generation immune-based therapies for patients with cancer.
High pressure growth of bulk GaN from solutions in gallium (2001)

In this paper, the growth of GaN single crystals from solutions of atomic nitrogen in liquid gallium under high N2 pressure is described. GaN single crystals obtained by the high nitrogen pressure solution method, without an intentional seeding, show strong growth anisotropy, which results in their platelet shape. The attempts to enhance the growth into (0001) directions by the increase of the integral supercooling in the solution often lead to growth instabilities on both N-polar and Ga-polar (0001) surfaces. This can be avoided only by the precise control of the growth conditions at the crystallization front on the particular surface.
Perspective on Optical Biosensors and Integrated Sensor Systems (2008)

Optical biosensors have begun to move from the laboratory to the point of use. This trend will be accelerated by new concepts for molecular recognition, integration of microfluidics and optics, simplified fabrication technologies, improved approaches to biosensor system integration, and dramatically increased awareness of the applicability of sensor technology to improve public health and environmental monitoring. Examples of innovations are identified that will lead to smaller, faster, cheaper optical biosensor systems with capacity to provide effective and actionable information.
Skin absorption enhancers. (1992)

When we try to maximize drug flux through the skin, we usually meet major difficulties because of the impervious nature of the stratum corneum. A popular solution incorporates penetration enhancers into transdermal products. Such materials ideally possess the sole property of reversibly reducing the barrier resistance of the horny layer, allowing the drug to reach the living tissues at a greater rate. This article considers examples of accelerant action that support a general concept explaining enhancer activity in human skin. The core of the proposal is that enhancers usually work by one or more of three main mechanisms: alteration of the lipid or protein domains of the stratum corneum or increase in tissue partitioning of a drug, a coenhancer, water, or any combination of these three chemicals. We may usefully refer to the overall hypothesis as the lipid-protein-partitioning (LPP) concept.
Potential Use of Nanocarriers With Pentacyclic Triterpenes in Cancer Treatments (2016)

Ursolic, oleanolic and betulinic acids are representative pentacyclic triterpenoids found in various plants and fruits. Despite having marked antitumor potentials, the very poor water solubility of these triterpenes hinders treatment development. Nanotechnology can enhance solubility, stability, bioavailability and phytochemical delivery, improving the therapeutic efficiency of triterpenes. This review focuses on the formulation, characterization and in vitro/in vivo evaluation of several delivery nanosystems used to enhance the physicochemical properties of ursolic, oleanolic and betulinic acids.
Nutritional characteristics of DAG oil (2003)

Excess calorie intake in industrialized countries has prompted development of fat substitutes and other lower-calorie dietary items to enhance health. DAG cooking oils, with a 1,3 configuration, taste and have the texture of commonly used TAG cooking oils. Because they are not hydrolyzed to 2-MAG in the gut, the absorption and metabolism of DAG oil differs from that of TAG. Among the physiological differences are lower postprandial lipemia and an increased proportion of FA being oxidized instead of stored. Preliminary studies suggest that these differences in energy partitioning between DAG and TAG may be usefully exploited to reduce the amount of fat stored from cooking oil and oil components of food items. Over 70 million bottles of DAG oil have been sold in Japan since its introduction in February 1999, and the product is being test-marketed in the United States. It is hoped that wider use of DAG oil may provide one additional means of preventing obesity.
Minor Groove Binder-Conjugated DNA Probes for Quantitative DNA Detection by Hybridization-Triggered Fluorescence (2002)

Here we describe the properties of a novel class of oligonucleotide probes capable of sensitive hybridization-triggered fluorescence. These fluorogenic probes, known commercially as MGB Eclipse probes, are characterized by having a conjugated minor groove binder (MGB) ligand at the 5'-end and a fluorophore at the 3'-end. Additionally, they have an efficient quencher moiety at the 5'-end that is useful with a wide variety of fluorescent dyes. Fluorescence of the single-stranded MGB Eclipse probe is efficiently quenched by the interaction of the terminal dye and quencher groups when not hybridized. Upon hybridization to a complementary target, the MGB molecule folds into duplex and hyper-stabilizes it, allowing the use of shorter, more specific probe sequences. The 5'-MGB-quencher group also prevents nuclease digestion by Taq DNA polymerase during PCR. Because of the hybridization-triggered fluorescence and the excellent specificity imparted by the MGB, these 5'-MGB Eclipse probes have great versatility for real-time PCR applications. The high sensitivity and specificity are illustrated using single nucleotide polymorphism detection, viral load determination, and gene expression analysis.
Circle-to-circle amplification for precise and sensitive DNA analysis (2004)

We present a tightly controlled process for strand-specific amplification of circularized DNA molecules. Tandem repeated complements of DNA circles are generated by rolling-circle replication, and converted to monomer circles of opposite polarity to that of the starting material. These circles are then subjected to one more round of rolling-circle replication and circularization, and the process can be further repeated. The method can be directed to produce single-stranded circular or linear monomers, or linear concatemers of the desired polarity. The reaction is not product inhibited, and can yield approximately 100-fold higher concentrations of monomer products than PCR. Each generation of the amplification process proceeds in a linear fashion, ensuring precise quantification. The procedure is suitable for parallel amplification of large numbers of DNA circles, because the few cycles and the robust reaction mechanism preserves the proportion of amplified molecules. We demonstrate the utility of the method for multiplexed genotyping of polymorphic loci and for quantitative DNA analysis.
T cell Bim levels reflect responses to anti–PD-1 cancer therapy (2016)

Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1<sup>+</sup>CD11a<sup>hi</sup>CD8<sup>+</sup>) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti-PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti-PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti-PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8<sup>+</sup> T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti-PD-1 therapy, although future prospective analyses are needed to validate its utility.
Monte Carlo simulation of substrate enhanced electron injection in split-gate memory cells (2005)

In this paper, we use fullband Monte Carlo simulations and gate current measurements to investigate charge injection in split-gate memory cells under negative substrate bias. It is shown that, in the source-side-injection (SSI) regime, the enhancement of the programming efficiency due to the substrate bias is low, unless very low drain and floating-gate biases are considered. In particular, the enhancement of the efficiency is largely reduced if the drain current is kept constant when comparing different substrate biases. Furthermore, it is observed that the carrier injection profile under negative substrate bias is broader than in the SSI regime, and a substantial amount of charge is injected in the spacer region.