gebhart/patrepeval huggingface dataset:
Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus (2017)

Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raise serious concerns regarding preparedness to combat this emerging virus. We used a virus-like particle (VLP)-based approach to develop a vaccine and a microneutralization assay for ZIKV. A synthetic capsid-premembrane-envelope (C-prM-E) gene construct of ZIKV was used to generate reporter virus particles (RVPs) that package a green fluorescent protein (GFP) reporter-expressing West Nile virus (WNV) replicon. The assay was adapted to a 96-well format, similar to the plaque reduction neutralization test (PRNT), and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While the ZIKV prM-E construct alone was sufficient for generating VLPs, efficient VLP production from the C-prM-E construct could be achieved in the presence of the WNV NS2B-3 protease, which cleaves C from prM, allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than those with the DNA vaccines, with C-prM-E VLPs giving slightly higher titers than those with prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective, and economical VLP-based vaccine against ZIKV.<b>IMPORTANCE</b> To address the growing Zika virus epidemic, we undertook this study with two objectives: first, to develop a safe, effective, and economical vaccine for ZIKV, and second, to develop a rapid and versatile assay to detect the anti-ZIKV immune response. We generated a cell line stably expressing ZIKV prM-E that produces large amounts of VLPs in the supernatant and a ZIKV C-prM-E cell line that produces reporter virus particles upon transfection with a GFP replicon plasmid. The prM-E VLPs induced a strong neutralizing antibody response in mice that was better when the capsid was included. VLP-based vaccines showed significantly better neutralizing antibody responses than those with their DNA counterparts. The RVP-based microneutralization assay worked similarly to the PRNT assay, with a rapid GFP readout in a 96-well format. Our VLP-based platform provides a source for a ZIKV vaccine and diagnosis that can rapidly be adapted to current outbreaks.
Restriction Primer Extension Method of Labeling Oligonucleotide Probes and Its Application to the Detection of HB E Genes (1988)

A new method for labeling oligonucleotides was developed to obtain high specific activity of radioactive probes. In an oligonucleotide molecule, two sequences were designed. One sequence, the 5', contains 19 nucleotides and serves as a template for probe synthesis. The second sequence, 3', contains a consensus sequence which forms a Pst I site after forming a complementary strand with the primer. In the presence of E. coli DNA polymerase I (Klenow fragment), alpha-32P dNTP and other dNTPs, a radioactive labeled oligonucleotide was synthesized by the primer extension method. After Pst I digestion, the probe was different from its template in length by 4 bp and could be separated from each other on urea-polyacrylamide gel electrophoresis (PAGE). A radioactive oligonucleotide probe with extremely high specific activity up to 10(10) dpm/micrograms could be obtained by the use of this method. The oligonucleotide probes have been used for the detection of the Hb E mutation in this report.
Experimental Comparison of Representation Methods and Distance Measures for Time Series Data (2010)

The previous decade has brought a remarkable increase of the interest in applications that deal with querying and mining of time series data. Many of the research efforts in this context have focused on introducing new representation methods for dimensionality reduction or novel similarity measures for the underlying data. In the vast majority of cases, each individual work introducing a particular method has made specific claims and, aside from the occasional theoretical justifications, provided quantitative experimental observations. However, for the most part, the comparative aspects of these experiments were too narrowly focused on demonstrating the benefits of the proposed methods over some of the previously introduced ones. In order to provide a comprehensive validation, we conducted an extensive experimental study re-implementing eight different time series representations and nine similarity measures and their variants, and testing their effectiveness on thirty-eight time series data sets from a wide variety of application domains. In this paper, we give an overview of these different techniques and present our comparative experimental findings regarding their effectiveness. In addition to providing a unified validation of some of the existing achievements, our experiments also indicate that, in some cases, certain claims in the literature may be unduly optimistic.
Stereospecificity in the Reaction of Tetrahydro-.beta.-carboline-3-carboxylic Acids with Isocyanates and Isothiocyanates. Kinetic vs Thermodynamic Control (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereospecificity in the Reaction of Tetrahydro-.beta.-carboline-3-carboxylic Acids with Isocyanates and Isothiocyanates. Kinetic vs Thermodynamic ControlMaria L. Lopez-Rodriguez, M. Jose Morcillo, Mercedes Garrido, Bellinda Benhamu, Virginia Perez, and Jose G. de la CampaCite this: J. Org. Chem. 1994, 59, 6, 1583–1585Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/jo00085a054https://doi.org/10.1021/jo00085a054research-articleACS PublicationsRequest reuse permissionsArticle Views278Altmetric-Citations18LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Flavor chemistry of 2-methyl-3-furanthiol, an intense meaty aroma compound (2012)

Volatile compounds containing sulfur make very important contributions to the aromas associated with various foods, and often define the characteristic flavor of the food. Thiols are especially potent; some have the lowest aroma thresholds of any food odorant. In this review, we focused on 2-methyl-3-furanthiol (MFT) which is a potent meaty flavor. We summarized the natural occurrence of MFT in a variety of meat products, together with its common isolation and detection techniques. MFT is generated in food processing in different pathways, among which Maillard reaction between carbohydrates and cysteine is the most common. Other than that it can also be formed from thiamin degradation or enzymatic reactions. Being unstable, MFT readily reacts with different components in food systems including forming disulfides through radical reactions or interacting with melanoidins through ionic reactions. MFT also has good antioxidant activities, in both aqueous and organic systems and can protect from lipid peroxidation. The metabolism of MFT in rat liver is also discussed.
NMDA receptor function, memory, and brain aging (2000)

An increasing level of N-methyl-D-aspartate (NMDA) receptor hypofunction within the brain is associated with memory and learning impairments, with psychosis, and ultimately with excitotoxic brain injury. As the brain ages, the NMDA receptor system becomes progressively hypofunctional, contributing to decreases in memory and learning performance. In those individuals destined to develop Alzheimer's disease, other abnormalities (eg, amyloidopathy and oxidative stress) interact to increase the NMDA receptor hypofunction (NRHypo) burden. In these vulnerable individuals, the brain then enters into a severe and persistent NRHypo state, which can lead to widespread neurodegeneration with accompanying mental symptoms and further cognitive deterioration. If the hypotheses described herein prove correct, treatment implications may be considerable. Pharmacological methods for preventing the overstimulation of vulnerable corticolimbic pyramidal neurons developed in an animal model may be applicable to the prevention and treatment of Alzheimer's disease.
Analysis of the Composition of Lipid in Human Meibum from Normal Infants, Children, Adolescents, Adults, and Adults with Meibomian Gland Dysfunction Using1H-NMR Spectroscopy (2011)

The changes in cholesteryl ester could be used as a molecular marker for MGD and could potentially be applied to follow the efficacy of drug therapy in the treatment of MGD. The similarity of the levels of cholesteryl esters in infant meibum and Md suggests that the relative amounts of these meibum components alone are unlikely to be responsible for the increased stability of the infant tear film and decreased stability of the tear film with MGD. This study reveals the complexity of human MLs and the changes that occur with age and disease. Understanding the factors that lead to such variations is of utmost relevance in the design of effective therapies.
Some advantages of curing mice bearing a large subcutaneous MOPC-315 tumor with a low dose rather than a high dose of cyclophosphamide. (1983)

Mice bearing a large s.c. MOPC-315 tumor can be cured by a dose of cyclophosphamide (CY) ranging from 15 to 200 mg/kg. However, the low (15 mg/kg) and the high (200 mg/kg) doses mediate tumor eradication via different mechanisms. Tumor eradication by the low dose of drug requires the cooperation of the toxic effect of the drug and T-cell-dependent antitumor immunity. On the other hand, tumor eradication by the high dose of drug does not require the participation of antitumor immunity but depends primarily on the tumoricidal activity of the drug. Spleen cells from tumor-bearing mice treated with the low dose of CY exhibit an augmented antitumor immune potential, whereas spleen cells from tumor-bearing mice treated with the high dose of CY exhibit suppressed antitumor immune potential. More importantly, tumor-bearing mice treated with the low dose of drug are able to reject a challenge with 300 times the minimal lethal tumor dose given 1, 6, or 31 days after CY therapy, whereas mice treated with the high dose of drug are unable to reject such a challenge given within the same time intervals after CY therapy. Moreover, when mice bearing a large tumor are treated with the high dose of CY and subsequently challenged again with tumor cells to establish a Day 4 nonpalpable tumor, this tumor is less responsive to cure by combined chemoimmunotherapy than is a Day 4 nonpalpable tumor established in normal mice. Thus, although the high dose of CY can cure most mice bearing a large-size MOPC-315 tumor, it not only does not result in antitumor immunity, but it actually reduces the effectiveness of chemoimmunotherapy for a second tumor challenge. In contrast, mice cured with the low dose of CY exhibit long-lasting potent antitumor immunity.
GTPase Activating Specificity of RGS12 and Binding Specificity of an Alternatively Spliced PDZ (PSD-95/Dlg/ZO-1) Domain (1998)

Regulator of G-protein signaling (RGS) proteins increase the intrinsic guanosine triphosphatase (GTPase) activity of G-protein alpha subunits in vitro, but how specific G-protein-coupled receptor systems are targeted for down-regulation by RGS proteins remains uncharacterized. Here, we describe the GTPase specificity of RGS12 and identify four alternatively spliced forms of human RGS12 mRNA. Two RGS12 isoforms of 6.3 and 5.7 kilobases (kb), encoding both an N-terminal PDZ (PSD-95/Dlg/ZO-1) domain and the RGS domain, are expressed in most tissues, with highest levels observed in testis, ovary, spleen, cerebellum, and caudate nucleus. The 5.7-kb isoform has an alternative 3' end encoding a putative C-terminal PDZ domain docking site. Two smaller isoforms, of 3.1 and 3.7 kb, which lack the PDZ domain and encode the RGS domain with and without the alternative 3' end, respectively, are most abundantly expressed in brain, kidney, thymus, and prostate. In vitro biochemical assays indicate that RGS12 is a GTPase-activating protein for Gi class alpha subunits. Biochemical and interaction trap experiments suggest that the RGS12 N terminus acts as a classical PDZ domain, binding selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the interleukin-8 receptor B (CXCR2) and the alternative 3' exon form of RGS12. The presence of an alternatively spliced PDZ domain within RGS12 suggests a mechanism by which RGS proteins may target specific G-protein-coupled receptor systems for desensitization.
Algorithm evolution with internal reinforcement for signal understanding (1998)

Automated program evolution has existed in some form for almost forty years. Signal understanding (e.g., signal classification) has been a scientific concern for longer than that. Generating a general machine learning signal understanding system has more recently attracted considerable research interest. First, this thesis defines and creates a general machine learning approach for signal understanding independent of the signal's type and size. This is accomplished through an evolutionary strategy of signal understanding programs that is an extension of genetic programming. Second, this thesis introduces a suite of sub-mechanisms that increase the power of genetic programming and contribute to the understanding of the learning technique developed. 
The central algorithmic innovation of this thesis is the process by which a novel principled credit-blame assignment is introduced and incorporated into the evolution of algorithms, thus improving the evolutionary process. This principled credit-blame assignment is done through a new program representation called neural programming and applied through a set of principled processes collectively called internal reinforcement in neural programming . This thesis concentrates on these algorithmic innovations in real world signal domains where the signals are typically large and/or poorly understood. 
This evolutionary learning of algorithms takes place in PADO , a system developed in this thesis for “parallel algorithm discovery and orchestration” and as a demonstrably effective strategy for divide-and-conquer in signal classification domains. This thesis includes an extensive empirical evaluation of the techniques developed in a rich variety of real-world signals. The results obtained demonstrate, among other things, the effectiveness of principled credit-blame assignment in algorithm evolution. 
This work is unique in three aspects. No other currently existing system can learn to classify or otherwise “symbolize” signals with no space or size penalties for the signal's size or type. No other system based on genetic programming currently exists that purposefully generates and orchestrates a variety of experts along problem specific lines. And, most centrally, the thesis introduces the first analytically sound mechanism for explaining and reinforcing specific parts of an evolving program. 
The goal of this thesis is to argue, explain, and demonstrate how representation and search are intimately connected in evolutionary computation and to address these dual concerns in the context of the evolution of Turing complete programs. Ideally, this thesis will inspire future research in this same area and along similar lines.
Habitat Fragmentation, Species Loss, and Biological Control (1994)

Fragmentation of habitats in the agricultural landscape is a major threat to biological diversity, which is greatly determined by insects. Isolation of habitat fragments resulted in decreased numbers of species as well as reduced effects of natural enemies. Manually established islands of red clover were colonized by most available herbivore species but few parasitoid species. Thus, herbivores were greatly released from parasitism, experiencing only 19 to 60 percent of the parasitism of nonisolated populations. Species failing to successfully colonize isolated islands were characterized by small and highly variable populations. Accordingly, lack of habitat connectivity released insects from predator control.
A Novel PD-L1-targeting Antagonistic DNA Aptamer With Antitumor Effects (2016)

The PD-1/PD-L1 axis is a major pathway involved in tumor immune evasion. Here, we report the novel PD-L1 antagonizing DNA aptamer (aptPD-L1) and demonstrate an integrated pipeline that expedites therapeutic aptamer development. Aptamer can exert antibody-mimic functions and is advantageous over antibody for its chemically synthetic nature, low immunogenicity, and efficient tissue penetration. Our results showed that aptPD-L1 blocked the binding between human PD-1 and PD-L1. Experiments using murine models showed that aptPD-L1 promoted in vitro lymphocyte proliferation and suppressed in vivo tumor growth without the induction of observable liver or renal toxicity. Analyses on the aptPD-L1-treated tumors further revealed elevated levels of infiltrating CD4<sup>+</sup> and CD8<sup>+</sup> T cells, intratumoral IL-2, TNF-α, interferon (IFN)-γ and the C-X-C motif chemokines, CXCL9 and CXCL10. The CD8<sup>+</sup> T cells in the aptPD-L1-treated tumors had higher CXCR3 expression level compared to the random-sequence oligonucleotides-treated ones. Besides, the length and density of CD31<sup>+</sup> intratumoral microvessels were significantly decreased in the aptPD-L1 treatment group. Collectively, our data suggested that aptPD-L1 helps T cell function restoration and modifies tumor microenvironment. These chemokines might orchestrate together to attract more T cells into the tumor tissues to form the positive amplification loop against tumor growth, indicating the translational potential of aptPD-L1 in cancer immunotherapy.
Minocycline Down-regulates MHC II Expression in Microglia and Macrophages through Inhibition of IRF-1 and Protein Kinase C (PKC)α/βII (2007)

Experimental allergic encephalomyelitis, an autoimmune disorder mediated by T cells, results in demyelination, inflammation, and axonal loss in the central nervous system (CNS). Microglia play a critical role in major histocompatibility complex class II (MHC II)-dependent antigen presentation and in reactivation of CNS-infiltrated encephalitogenic T cells. Minocycline, a tetracycline anti-biotic, has profound anti-inflammatory properties and is experimentally used for treatment of many CNS disorders; however, the mechanisms involved in minocycline effects remain unknown. We show that administration of minocycline for 2 weeks ameliorated clinical severity of experimental allergic encephalomyelitis, an effect that partially involves the down-regulation of MHC II proteins in the spinal cord. Therefore, we sought to elucidate the molecular mechanisms of minocycline inhibitory effects on MHC II expression in microglia. Although complex, the co-activator class II transactivator (CIITA) is a key regulator of MHC II expression. Here we show that minocycline inhibited interferongamma (IFNgamma)-induced CIITA and MHC II mRNA. Interestingly, however, it was without effect on STAT1 phosphorylation or IRF-1 expression, transcription factors that are activated by IFNgamma and necessary for CIITA expression. Further experiments revealed that MHC II expression is down-regulated in the presence of the PKC(alpha) inhibitor Gö6976. Minocycline inhibited IFNgamma-induced PKC(alpha/betaII) phosphorylation and the nuclear translocation of both PKC(alpha/betaII) and IRF-1 that subsequently inhibits CIITA expression. Our present data delineate a molecular pathway of minocycline action that includes inhibitory effects on PKC(alpha/betaII) and transcription factors that regulate the expression of critical inflammatory genes such as MHC II. Such a fundamental mechanism may underlie the pleiotropic effects of minocycline in CNS inflammatory disorders.
Surface-enhanced optical microscopy (1985)

A new concept is proposed for an optical probe with spatial resolution unlimited by diffraction effects. It is based on optical-field confinement by surface plasmons of a submicrometer-sized metal particle. The particle serves as an antenna that receives an incoming electromagnetic field. The field extends to a nearby sample surface and interacts with a small area on that surface through the nonlinear susceptibility tensors. The induced sample polarization is reradiated by the particle, thereby generating a Raman, a two-photon, or a second-harmonic spectrum. Microscopy is performed by rastering the position of the metal particle over the sample surface. Spatial resolution approaching 1 nm is projected. The concept is also applicable to submicrometer optical lithography and ultrahigh-density optical recording.
Why fat is bright in rare and fast spin‐echo imaging (1992)

Fast spin-echo (FSE) sequences are becoming popular for T2-weighted clinical imaging because they result in a severalfold reduction in imaging time and because they provide conventional spin-echo contrast for most tissues. Fat, however, has been observed to have anomalously high signal intensity on FSE images. The present study shows that the brighter fat results from the multiple 180 degrees refocusing pulses, which eliminate diffusion-mediated susceptibility dephasing and suppress J-coupling modulation of the echo train.
Minimization of Region-Scalable Fitting Energy for Image Segmentation (2008)

Intensity inhomogeneities often occur in real-world images and may cause considerable difficulties in image segmentation. In order to overcome the difficulties caused by intensity inhomogeneities, we propose a region-based active contour model that draws upon intensity information in local regions at a controllable scale. A data fitting energy is defined in terms of a contour and two fitting functions that locally approximate the image intensities on the two sides of the contour. This energy is then incorporated into a variational level set formulation with a level set regularization term, from which a curve evolution equation is derived for energy minimization. Due to a kernel function in the data fitting term, intensity information in local regions is extracted to guide the motion of the contour, which thereby enables our model to cope with intensity inhomogeneity. In addition, the regularity of the level set function is intrinsically preserved by the level set regularization term to ensure accurate computation and avoids expensive reinitialization of the evolving level set function. Experimental results for synthetic and real images show desirable performances of our method.