gebhart/patrepeval huggingface dataset:
Sensitization of Tumors for Attack by Virus-Specific CD8+ T-Cells Through Antibody-Mediated Delivery of Immunogenic T-Cell Epitopes (2019)

Anti-tumor immunity is limited by a number of factors including the lack of fully activated T-cells, insufficient antigenic stimulation and the immune-suppressive tumor microenvironment. We addressed these hurdles by developing a novel class of immunoconjugates, Antibody-Targeted Pathogen-derived Peptides (ATPPs), which were designed to efficiently deliver viral T-cell epitopes to tumors with the aim of redirecting virus-specific memory T-cells against the tumor. ATPPs were generated through covalent binding of mature MHC class I peptides to antibodies specific for cell surface-expressed tumor antigens that mediate immunoconjugate internalization. By means of a cleavable linker, the peptides are released in the endosomal compartment, from which they are loaded into MHC class I without the need for further processing. Pulsing of tumor cells with ATPPs was found to sensitize these for recognition by virus-specific CD8+ T-cells with much greater efficiency than exogenous loading with free peptides. Systemic injection of ATPPs into tumor-bearing mice enhanced the recruitment of virus-specific T-cells into the tumor and, when combined with immune checkpoint blockade, suppressed tumor growth. Our data thereby demonstrate the potential of ATPPs as a means of kick-starting the immune response against "cold" tumors and increasing the efficacy of checkpoint inhibitors.
Hydrophobic Shielding of Outer Surface: Enhancing the Chemical Stability of Metal–Organic Polyhedra (2018)

Metal-organic polyhedra (MOP) are a promising class of crystalline porous materials with multifarious potential applications. Although MOPs and metal-organic frameworks (MOFs) have similar potential in terms of their intrinsic porosities and physicochemical properties, the exploitation of carboxylate MOPs is still rudimentary because of the lack of systematic development addressing their chemical stability. Herein we describe the fabrication of chemically robust carboxylate MOPs via outer-surface functionalization as an a priori methodology, to stabilize those MOPs system where metal-ligand bond is not so strong. Fine-tuning of hydrophobic shielding is key to attaining chemical inertness with retention of the framework integrity over a wide range of pH values, in strong acidic conditions, and in oxidizing and reducing media. These results are further corroborated by molecular modelling studies. Owing to the unprecedented transition from instability to a chemically ultra-stable regime using a rapid ambient-temperature gram-scale synthesis (within seconds), a prototype strategy towards chemically stable MOPs is reported.
Prognostic impact of circulating tumor cell apoptosis and clusters in serial blood samples from patients with metastatic breast cancer in a prospective observational cohort (2016)

Patients with a continuous presence of apoptotic or clustered CTCs in FU samples after systemic therapy initiation had worse prognosis than patients without these CTC characteristics. In patients with ≥5 CTC/7.5 ml blood at BL, morphologic characterization of persistent CTCs could be an important prognostic marker during treatment, in addition to CTC enumeration alone. Clinical Trials (NCT01322893), registration date 21 March 2011.
Multiplicity of Leucine Transport Systems in Escherichia coli K-12 (1973)

The major component of leucine uptake in Escherichia coli K-12 is a common system for l-leucine, l-isoleucine, and l-valine (LIV-I) with a Michaelis constant (K(m)) value of 0.2 muM (LIV-I system). The LIV-binding protein appears to be associated with this system. It now appears that the LIV-I transport system and LIV-binding protein also serve for the entry of l-alanine, l-threonine, and possibly l-serine. A minor component of l-leucine entry occurs by a leucine-specific system (L-system) for which a specific leucine-binding protein has been isolated. A mutant has been obtained that shows increased levels of the LIV-I transport activity and increased levels of both of the binding proteins. Another mutant has been isolated that shows only a major increase in the levels of the leucine-specific transport system and the leucine-specific binding protein. A third binding protein that binds all three branched-chain amino acids but binds isoleucine preferentially has been identified. The relationship of the binding proteins to each other and to transport activity is discussed. A second general transport system (LIV-II system) with a K(m) value of 2 muM and a relatively low V(max) can be observed in E. coli. The LIV-II system is not sensitive to osmotic shock treatment nor to growth of cells in the presence of leucine. This high K(m) system, which is specific for the branched-chain amino acids, can be observed in membrane vesicle preparations.
REVIEW ■ : ATP-sensitive Potassium Channels: Diverse Functions in the Central Nervous System (1996)

ATP-sensitive potassium channels open when cytoplasmic levels of ATP drop, thus linking membrane potential to the metabolic state of the cell. Cloning studies have suggested that these channels are related structurally to the inward rectifier family of potassium channels, with two putative membrane-spanning regions. Sulfonylurea drugs, which are used in the treatment of diabetes, inhibit these channels by binding to an associated membrane protein. Other drugs, including some vasodilators, activate ATP-sensitive potassium channels. Diverse neurotransmitter and hormone receptors can modulate these channels, in some cases through interactions with guanyl nucleotide binding proteins. There appear to be multiple subtypes of these channels, differing in electrical properties as well as in drug sensitivities. In the brain, these channels appear to play a role in mediating satiety after feeding. They also function in neurons to protect against excitotoxicity, by counteracting the membrane depolarization associated with metabolic stress. Brain dopamine receptors appear to modulate a novel subtype of ATP-sensitive potassium channel. The association of dopamine receptors with a mechanism involved in protection against neurodegeneration may have implications for the causes of diseases in which dopaminergic regions of brain undergo structural changes, possibly including schizophrenia. NEUROSCIENTIST 2:145-152, 1996
A temporal logic for reasoning about processes and plans (1982)

Much previous work in artificial intelligence has neglected representing time in all its complexity. In particular, it has neglected continuous change and the indeterminacy of the future. To rectify this, I have developed a first-order temporal logic, in which it is possible to name and prove things about facts, events, plans, and world histories. In particular, the logic provides analyses of causality, continuous change in quantities, the persistence of facts (the frame problem), and the relationship between tasks and actions. It may be possible to implement a temporal-inference machine based on this logic, which keeps track of several “maps” of a time line, one per possible history.
Integration of Optimized Substituent Patterns to Produce Highly Potent 4‐Aryl‐pyridine Glucagon Receptor Antagonists. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Evaluating the quality of anonymous record linkage using deterministic procedures with the New York state aids registry and a hospital discharge file (1995)

Linkage of same-person records across multiple databases relies on high-quality, uniformly available identifying information. These data quality issues become increasingly important when personal names are not available for record linkage. Using deterministic decision criteria, we linked records from two population-based files in the absence of personal names. The sensitivity of anonymous record linkage procedures ranged from 32 to 85 per cent for the two years studied, and the positive predictive value (PPV) ranged from 14 to 99 per cent. Decreasing sensitivity and PPV were primarily attributed to (1) errors in computerized identifying information and (2) the deterministic decision criteria specified for record linkage. An evaluation of the contribution of personal names to the quality of record linkage found no measurable impact.
Perceptual image quality improvement for large screen displays (2006)

To display a low-resolution digital image on a large screen display with a native resolution that reaches or exceeds the well-known HDTV standard, it is desirable to re-scale the image to full screen resolution. However, many well known re-scale algorithms, such as cubic spline interpolation or bi-cubic interpolation filters, only reach limited performance in terms of perceived sharpness and leave contour artifacts like jaggedness or haloing, which easily appear above the threshold of visual perception with regard to a reduced viewing distance. Since human vision demonstrates a non-linear behavior towards the detection of these artifacts, we elaborate some simple image operations that better adapt to the image quality constraints imposed by most of the linear methods known to us today. In particular, we propose a nonlinear method that can reduce or hide the above-mentioned contour artifacts in the spatial frequency domain of the display raster and increase perceived sharpness to a very noticeable degree. As a result, low-resolution images look better on large screen displays due to an enhanced local contrast and show less annoying artifacts than some of the classical approaches reviewed in this paper.
Self-assembling RNA square (2011)

The three-dimensional structures of noncoding RNA molecules reveal recurring architectural motifs that have been exploited for the design of artificial RNA nanomaterials. Programmed assembly of RNA nanoobjects from autonomously folding tetraloop-receptor complexes as well as junction motifs has been achieved previously through sequence-directed hybridization of complex sets of long oligonucleotides. Due to size and complexity, structural characterization of artificial RNA nanoobjects has been limited to low-resolution microscopy studies. Here we present the design, construction, and crystal structure determination at 2.2 Å of the smallest yet square-shaped nanoobject made entirely of double-stranded RNA. The RNA square is comprised of 100 residues and self-assembles from four copies each of two oligonucleotides of 10 and 15 bases length. Despite the high symmetry on the level of secondary structure, the three-dimensional architecture of the square is asymmetric, with all four corners adopting distinct folding patterns. We demonstrate the programmed self-assembly of RNA squares from complex mixtures of corner units and establish a concept to exploit the RNA square as a combinatorial nanoscale platform.
Robust and Efficient, Yet Uncatalyzed, Synthesis of Trialkylsilyl-Protected Cyanohydrins from Ketones (2008)

High-yielding cyanosilylation of ketones with NaCN and various chlorotrialkylsilanes in DMSO proceeds smoothly without catalysis to give silyl-protected ketone cyanohydrins. The unique role of DMSO consists in rendering naked cyanide anions that reversibly add to the C double bond O bond at the rate-determining step followed by fast trapping of the transient tertiary sodium cyanoalcoholates with chlorotrialkylsilanes or in situ generated cyanotrialkylsilanes. Preparatively, the reaction matches the best known catalytic cyanosilylation systems applying expensive Me(3)SiCN and demonstrates unprecedented efficiency in the synthesis of sterically congested trialkylsilyl-protected cyanohydrins.
Fibromyalgia: Where are we a decade after the American College of Rheumatology classification criteria were developed? (2002)

No abstract.
Critical Role of Calpain-mediated Cleavage of Calcineurin in Excitotoxic Neurodegeneration (2004)

Calcineurin and calpain, a Ca2+/calmodulin-dependent protein phosphatase and a Ca2+-dependent cysteine protease, respectively, mediate neuronal cell death through independent cascades. Here, we report that during neuroexcitotoxicity, calcineurin A (CnA) is directly cleaved by calpain in vitro and in vivo, resulting in the enzyme being converted to an active form. Mass spectrometry identified three cleavage sites in CnA, two of which were constitutively active forms. Overexpression of the cleaved CnA induced caspase activity and neuronal cell death. Calpain inhibitors and membrane-permeable calpastatin peptides not only blocked the cleavage of CnA, but also protected against excitotoxic neuronal cell death in vitro and in vivo. These results indicate that CnA is a crucial target for calpain, and the calpain-mediated activation of CnA triggers excitotoxic neurodegeneration. This study established a molecular link between calpain and calcineurin, thereby demonstrating a new mechanism for proteolytical regulation of calcineurin by calpain in response to certain pathological states.
Maternal-fetal transfer of immunoglobulins. (1995)

Immunoglobulins are transferred through the placenta in an active, selective and affinity-restricted process, which is Fc-gamma receptor mediated and intracellular. Much work is still required to improve our ability to control the rate and the efficiency of this process, but the results of pioneering attempts have been encouraging.
Digital Microfluidics (2012)

Digital microfluidics (DMF) is an emerging liquid-handling technology that enables individual control over droplets on an open array of electrodes. These picoliter- to microliter-sized droplets, each serving as an isolated vessel for chemical processes, can be made to move, merge, split, and dispense from reservoirs. Because of its unique advantages, including simple instrumentation, flexible device geometry, and easy coupling with other technologies, DMF is being applied to a wide range of fields. In this review, we summarize the state of the art of DMF technology from the perspective of analytical chemistry in sections describing the theory of droplet actuation, device fabrication and integration, and applications.
Hot Carrier-Assisted Intrinsic Photoresponse in Graphene (2011)

Graphene is a new material showing high promise in optoelectronics, photonics, and energy-harvesting applications. However, the underlying physical mechanism of optoelectronic response has not been established. Here, we report on the intrinsic optoelectronic response of high-quality dual-gated monolayer and bilayer graphene p-n junction devices. Local laser excitation at the p-n interface leads to striking six-fold photovoltage patterns as a function of bottom- and top-gate voltages. These patterns, together with the measured spatial and density dependence of the photoresponse, provide strong evidence that non-local hot-carrier transport, rather than the photovoltaic effect, dominates the intrinsic photoresponse in graphene. This novel regime, which features a long-lived and spatially distributed hot carrier population, may open the doorway for optoelectronic technologies exploiting efficient energy transport at the nanoscale.
Two-Dimensional Polymerization of Lipid Bilayers: Rate of Polymerization of Acryloyl and Methacryloyl Lipids (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTwo-Dimensional Polymerization of Lipid Bilayers: Rate of Polymerization of Acryloyl and Methacryloyl LipidsJunting Lei and David F. O'BrienCite this: Macromolecules 1994, 27, 6, 1381–1388Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/ma00084a016https://doi.org/10.1021/ma00084a016research-articleACS PublicationsRequest reuse permissionsArticle Views112Altmetric-Citations24LEARN 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
CBP Activity Mediates Effects of the Histone Deacetylase Inhibitor Butyrate on WNT Activity and Apoptosis in Colon Cancer Cells (2013)

Mutations in the WNT/beta-catenin pathway are responsible for initiating the majority of colorectal cancers (CRCs). We have previously shown that hyperactivation of this signaling by histone deacetylase inhibitors (HDACis) such as butyrate, a fermentation product of dietary fiber, promotes CRC cell apoptosis. The extent of association between beta-catenin and the transcriptional coactivator CREB-binding protein (CBP) influences WNT/catenin signaling and, therefore, colonic cell physiology. CBP functions as a histone acetylase (HAT); therefore, we hypothesized that the modulation of WNT/catenin activity by CBP modifies the ability of the HDACi butyrate to hyperinduce WNT signaling and apoptosis in CRC cells. Our findings indicate that CBP affects the hyperinduction of WNT activity by butyrate. ICG-001, which specifically blocks association between CBP and beta-catenin, abrogates the butyrate-triggered increase in the number of CRC cells with high levels of WNT/catenin signaling. Combination treatment of CRC cells with ICG-001 and butyrate results in cell type-specific effects on apoptosis. Further, both butyrate and ICG-001 repress CRC cell proliferation, with additive effects in suppressing cell growth. Our study strongly suggests that ICG-001-like agents would be effective against butyrate/HDACi-resistant CRC cells. Therefore, ICG-001-like agents may represent an important therapeutic option for CRCs that exhibit low-fold hyperactivation of WNT activity and apoptosis in the presence of HDACis. The findings generated from this study may lead to approaches that utilize modulation of CBP activity to facilitate CRC therapeutic or chemopreventive strategies.
Multilayer array antennas with integrated frequency selective surfaces conformal to a circular cylindrical surface (2005)

In this paper, we present the analysis of periodic arrays on cylindrical surfaces using open-ended waveguide radiators loaded with radomes and frequency selective surfaces (FSS). The multilayer structure can be used to obtain a filtering behavior by properly choosing the radomes and the size of the FSS apertures. The effect of the gradual cutoff properties of the cylindrical waves is also addressed and the design of a number of filtering structures including one or two FSS is presented.
GENETICS OF EUBACTERIAL CAROTENOID BIOSYNTHESIS: A Colorful Tale (1997)

Carotenoids represent one of the most widely distributed and structurally diverse classes of natural pigments, with important functions in photosynthesis, nutrition, and protection against photooxidative damage. In the eubacterial community, yellow, orange, and red carotenoids are produced by anoxygenic photosynthetic bacteria, cyanobacteria, and certain species of nonphotosynthetic bacteria. Many eukaryotes, including all algae and plants, as well as some fungi, also synthesize these pigments. In noncarotenogenic organisms, such as mammals, birds, amphibians, fish, crustaceans, and insects, dietary carotenoids and their metabolites also serve important biological roles. Within the last decade, major advances have been made in the elucidation of the molecular genetics, the biochemistry, and the regulation of eubacterial carotenoid biosynthesis. These developments have important implications for eukaryotes, and they make increasingly attractive the genetic manipulation of carotenoid content for biotechnological purposes.
Increased matrix metalloproteinase-2 expression and reduced tissue factor pathway inhibitor-2 expression correlate with angiogenesis and early postoperative recurrence of pancreatic carcinoma. (2015)

Matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 are known to influence tumor angiogenesis and progression. This work aimed to describe the levels of MMP-2 and TFPI-2 expression associated with tumor angiogenesis and early postoperative recurrence in patients with pancreatic carcinoma. Expression of MMP-2 and TFPI-2 in carcinoma tissues and paracarcinomatous tissues was assayed by immunostaining. Expression of vascular endothelial growth factor (VEGF) and CD34 in tumor tissues was also assayed by immunostaining. The correlations of MMP-2 and TFPI-2 with VEGF, microvessel density (MVD), and early postoperative recurrence were analyzed. The results showed that MMP-2 expression was significantly increased (P < 0.05) and TFPI-2 expression was significantly decreased (P < 0.001) in carcinoma tissues compared with paracarcinomatous tissues. MMP-2 expression was positively correlated with VEGF (r = 0.594, P < 0.001) and MVD (r = 0.432, P < 0.001) in carcinoma tissues. TFPI-2 expression was negatively correlated with VEGF (r = -0.654, P < 0.001) and MVD (r = -0.360, P < 0.001) in carcinoma tissues. Multivariate logistic regression analysis showed that up-regulated MMP-2 and down-regulated TFPI-2 were independent predictors of early postoperative recurrence of pancreatic carcinoma. Receiver operating characteristic curve analysis showed that the combination of MMP-2 and TFPI-2 was a reliable predictive model of early recurrence. We conclude that increased MMP-2 expression and reduced TFPI-2 expression are closely linked to angiogenesis and early postoperative recurrence of pancreatic carcinoma. Immunohistochemical assay of MMP-2 and TFPI-2 may be useful for predicting early relapse of pancreatic carcinoma after surgery.
TDP‐43 A315T mutation in familial motor neuron disease (2008)

To identify novel causes of familial neurodegenerative diseases, we extended our previous studies of TAR DNA-binding protein 43 (TDP-43) proteinopathies to investigate TDP-43 as a candidate gene in familial cases of motor neuron disease. Sequencing of the TDP-43 gene led to the identification of a novel missense mutation, Ala-315-Thr, which segregates with all affected members of an autosomal dominant motor neuron disease family. The mutation was not found in 1,505 healthy control subjects. The discovery of a missense mutation in TDP-43 in a family with dominantly inherited motor neuron disease provides evidence of a direct link between altered TDP-43 function and neurodegeneration.
Two‐step mechanism of inhibition of cathepsin B by cystatin C due to displacement of the proteinase occluding loop (1998)

Stopped-flow kinetics showed that the inhibition of the lysosomal cysteine proteinase, cathepsin B, by its endogenous inhibitor, cystatin C, occurs by a two-step mechanism, in which an initial, weak interaction is followed by a conformational change. The initial interaction most likely involves binding of the N-terminal region of the inhibitor to the proteinase. Considerable evidence indicates that the subsequent conformational change is due to the inhibitor displacing the occluding loop of the proteinase that partially obscures the active site. The presence of this loop, which allows the enzyme to function as an exopeptidase, thus complicates the inhibition mechanism, rendering cathepsin B much less susceptible than other cysteine proteinases to inhibition by cystatins.