gebhart/patrepeval huggingface dataset:
Cell-Permeable Peptide Inhibitors of JNK (2001)

Stress conditions and proinflammatory cytokines activate the c-Jun NH2-terminal kinase (JNK), a member of the stress-activated group of mitogen-activated protein kinases (MAPKs). We recently demonstrated that inhibition of JNK signaling with the use of the islet-brain (IB) 1 and 2 proteins prevented interleukin (IL)-1beta-induced pancreatic beta-cell death. Bioactive cell-permeable peptide inhibitors of JNK were engineered by linking the minimal 20-amino acid inhibitory domains of the IB proteins to the 10-amino acid HIV-TAT sequence that rapidly translocates inside cells. Kinase assays indicate that the inhibitors block activation of the transcription factor c-Jun by JNK. Addition of the peptides to the insulin-secreting betaTC-3 cell line results in a marked inhibition of IL-1beta-induced c-jun and c-fos expression. The peptides protect betaTC-3 cells against apoptosis induced by IL-1beta. All-D retro-inverso peptides penetrate cells as efficiently as the L-enantiomers, decrease c-Jun activation by JNK, and remain highly stable inside cells. These latter peptides confer full protection against IL-1beta-induced apoptosis for up to 2 weeks of continual treatment with IL-1beta. These data establish these bioactive cell-permeable peptides as potent pharmacological compounds that decrease intracellular JNK signaling and confer long-term protection to pancreatic beta-cells from IL-1beta-induced apoptosis.
THE FIRST GUN (2009)

They burned the old gun that used to stand in the dark corner up in the garret, close to the stuffed fox that always grinned so fiercely. Perhaps the reason why he seemed in such a ghastly rage was that he did not come by his death fairly. Otherwise his pelt would not have been so perfect. And why else was he put away up there out of sight?—and so magnificent a brush as he had too. But there he stood, and mounted guard over the old flintlock that was so powerful a magnet to us in those days. Though to go up there alone was no slight trial of moral courage after listening to the horrible tales of the carters in the stable, or the old women who used to sit under the hedge in the shade, on an armful of hay, munching their crusts at luncheon time.
Control of chromatic focal shift through wave-front coding (1998)

Control of chromatic aberration through purely optical means is well known. We present a novel, to our knowledge, optical-digital method of controlling chromatic aberration. The optical-digital system, which incorporates a cubic phase-modulation (CPM) plate in the optical system and postprocessing of the detected image, effectively reduces a system's sensitivity to misfocus in general or axial (longitudinal) chromatic aberration, in particular. A fully achromatic imaging system (one that is corrected for a continuous range of wavelengths) can be achieved by initial optimization of the optical system for all aberrations except chromatic aberration. The chromatic aberration is corrected by the inclusion of the CPM plate and postprocessing.
Why no one uses functional languages (1998)

To say that no one uses functional languages is an exaggeration. Phone calls in the European Parliament are routed by programs written in Ericsson's functional language Erlang. Virtual CDs are distributed on Cornell's network via the Ensemble system written in IN-RIA's CAML, and real CDs are shipped by Polygram in Europe using Software AG's Natural Expert. Functional languages are the language of choice for writing theorem provers, including the HOL system which helped debug the design of the HP 9000 line of multiprocessors. These applications and others are described in a previous column
A Cancer Research UK phase I study evaluating safety, tolerability, and biological effects of chimeric anti-CD40 monoclonal antibody (MAb), Chi Lob 7/4. (2010)

2507 Background: Expression of CD40 on a range of malignancies and the role of CD40 signaling in antigen presentation make it an attractive target for MAb therapy. Potential mechanisms of action for agonistic anti-CD40 include direct cytotoxic effects on tumor cells, recruitment of immune effectors and conditioning of antigen-presenting cells (Schultze and Johnson. Lancet, 1999. 354:1225). Preclinical studies showed anti-CD40 can eradicate lymphoma in immunocompetent hosts, inducing rapid CD8+ T-cell responses independent of CD4+ T-cell help. The response provided protection against re-challenge without further treatment. Notably, therapeutic activity improved when animals with a higher tumor burden were treated. (French et al Nat Med. 1999. 5:548). We have made an agonistic IgG1 chimeric anti-CD40 MAb, Chi Lob 7/4. The affinity is 0.2 nM, comparable to the parent murine MAb (0.1 nM). The aims of the study are to establish maximum tolerated dose (MTD), toxicity profile, biologically-active dose and pharmacokinetics, identify dose limiting toxicity and propose a dose for phase II evaluation. Methods: Eligible patients (pts) have histologically proven CD40+ solid tumors or diffuse large B-cell lymphoma resistant to conventional therapy. Chi Lob 7/4 is given by intravenous infusion weekly for 4 doses starting at 0.5 mg/dose. Planned dose escalation is in cohorts of 3 pts until MTD or biological effect, defined as reduction of peripheral blood CD19+ B-cells to 10% or less of baseline. Nineteen patients have been recruited to the dose escalation study, reaching 160 mg/dose. An expanded cohort at this dose will test efficacy in different tumor types. Enzyme linked immunosorbant assays were developed and validated to quantitate Chi-Lob 7/4 in serum and test for anti-chimeric MAb responses. Pharmacodynamic assessments include quantitation of T-, NK-, and B-cell numbers and activation in peripheral blood by flow cytometry, measurement of a panel of cytokines in plasma by Luminex technology, enumeration, and phenotypic assessment of human plasmacytoid and myeloid dendritic cells by a novel 6 color flow cytometry panel. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CancerResearch UK CancerResearch UK
Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells (1995)

Hyperphosphorylated tau protein is the major constituent of the paired helical filament (PHF), the major fibrous component of the neurofibrillary lesions of Alzheimer's disease (AD). Hyperphosphorylation of tau is believed to be the critical event that leads to filament assembly. Identification of the responsible protein kinases is therefore a key step towards an understanding of the pathogenesis of AD. Mitogen-activated protein kinase, glycogen synthase kinase-3 (GSK3) and neuronal cdc2-like kinase have been shown to phosphorylate tau protein in vitro at a number of sites that are phosphorylated in PHFs. In this study, we report that transient transfection of human GSK3 beta into Chinese hamster ovary cells stably transfected with individual human tau isoforms leads to hyperphosphorylation of tau at all the sites investigated with phosphorylation-dependent anti-tau antibodies. Thus, GSK3 beta is a protein kinase that phosphorylates tau protein in intact cells.
3'-terminal nucleotide sequence of encephalomyocarditis virus RNA determined by reverse transcriptase and chain-terminating inhibitors. (1978)

We have adapted the chain-termination method for determining the nucleotide sequence of DNA of Sanger, Nicklen, and Coulson [(1977) Proc. Natl. Acad. Sci. USA 74, 5463--5467] for use with reverse transcriptase (RNA-directed DNA nucleotidyltransferase) on RNA templates. With this method and using a primer (the octanucleotide pdT7rC) directed at the 3'-terminal poly(A), we have determined a sequence of 166 residues in the genomic RNA of the picornavirus encephalomyocarditis virus.
DNA-Dependent Kinase (p350) as a Candidate Gene for the Murine SCID Defect (1995)

Severe combined immunodeficient (SCID) mice are deficient in a recombination process utilized in both DNA double-strand break repair and in V(D)J recombination. The phenotype of these mice involves both cellular hypersensitivity to ionizing radiation and a lack of B and T cell immunity. The catalytic subunit of DNA-dependent protein kinase, p350, was identified as a strong candidate for the murine gene SCID. Both p350 and a gene complementing the SCID defect colocalize to human chromosome 8q11. Chromosomal fragments expressing p350 complement the SCID phenotype, and p350 protein levels are greatly reduced in cells derived from SCID mice compared to cells from wild-type mice.
Multilayered Poly(p-phenylenevinylene)/Reduced Graphene Oxide Film: An Efficient Organic Current Collector in an All-Plastic Supercapacitor (2014)

This article describes the preparation, using layer-by-layer deposition techniques, of an all-solid-state flexible in-plane supercapacitor based on a poly(ethylene terephthalate) (PET) substrate, laminated with two strata of ultrathin multilayer films composed of 30 polyaniline (PANi)/reduced graphene oxide (RGO) bilayers and 30 poly(p-phenylenevinylene) (PPV)/RGO bilayers. The influence of the (PPV/RGO)30 stratum on the electrochemical properties of the (PANi/RGO)30/(PPV/RGO)30 film (denoted P30) (d = 90.1 nm) supported on a PET was evaluated and compared to the corresponding influence of the (PANi/RGO)53 film (denoted P53) (d = 91.5 nm). The volumetric capacitance of P30 at a discharge current of 20 A/cm(3) (957 F/cm(3)) was much higher than that obtained from P53 (733 F/cm(3)), indicating that the (PPV/RGO)30 film performed well as a current collector. Furthermore, an all-solid-state flexible in-plane EC assembled with P30 electrodes in parallel mode (denoted EC30) exhibited an outstanding volumetric capacitance (152 F/cm(3) at 20 A/cm(3)) with a high energy density (9.4 mW h/cm(3)) and power density (6.5 W/cm(3)), compared to EC53 (assembled with P53). The electron-transfer resistance of the P30 electrode corresponded to only 59% of the P53's value (1.53 vs 2.60 kΩ cm(2)). The high capacitance of EC30 was attributed to the low internal resistance of P30, which resulted from the presence of additional in-plane electrical pathways in the electrode. The enhanced transport led to 85% capacitance retention by EC30 (69% for EC53) after a 1000 charge/discharge cycles test. The series resistance variations (ΔR/R0) of EC30 also indicated good electromechanical durability in the device, with a 5.0% increase in the resistance (contrasted with a 10.8% increase in EC53) over 1000 bending cycles at a minimum radius of 5 mm. The excellent electrochemical properties of EC30 may potentially meet the requirements for miniaturized electrodes in the manufacture of flexible, lightweight, mechanically durable microelectronic applications.
Carcinoembryonic antigen for the detection of recurrent disease following curative resection of colorectal cancer. (2001)

Our findings indicate that up to 47% of the patients with recurrent disease and 11% of all patients (N = 144, groups IIa + IIIb + IIIc) could benefit from routine follow-up CEA determinations after curative colorectal cancer resection. Nonetheless, only 2.3% of all patients with elevated CEA levels underwent R0 resection of recurrent disease. Despite these detection and R0 resectability rates, CEA plays a crucial role in the early detection of recurrent disease and remains an important part of routine patient care after curative resection of colorectal cancer.
Continuity in Evolution: On the Nature of Transitions (1998)

To distinguish continuous from discontinuous evolutionary change, a relation of nearness between phenotypes is needed. Such a relation is based on the probability of one phenotype being accessible from another through changes in the genotype. This nearness relation is exemplified by calculating the shape neighborhood of a transfer RNA secondary structure and provides a characterization of discontinuous shape transformations in RNA. The simulation of replicating and mutating RNA populations under selection shows that sudden adaptive progress coincides mostly, but not always, with discontinuous shape transformations. The nature of these transformations illuminates the key role of neutral genetic drift in their realization.
Antiproliferative Effects of Steric Blocking Phosphorodiamidate Morpholino Antisense Agents Directed against c- myc (2000)

The phosphorodiamidate Morpholino oligomers (PMO) are a new class of antisense agents that inhibit gene expression by binding to RNA and sterically blocking processing or translation. In a search for a Morpholino agent that would inhibit cell proliferation, it was found that oligomers directed against c-myc, a gene involved in control of the cell cycle, were effective. The sequence specificity and mechanism of action of one agent were determined. The 20-mer 126 lowers c-myc protein levels in treated cells and arrests cells in G0/G1 of the cell cycle. It also acts at the RNA level to inhibit normal pre-mRNA splicing and instead produces an aberrantly spliced mRNA. Irrelevant and mispair control oligomers indicated that the observed antiproliferative effect was sequence specific. This was confirmed in a reporter gene model system using a c-myc 5'-untranslated region (5'-UTR) fused to a cDNA copy of the insect luciferase gene. We conclude that 126 is acting through an antisense mechanism involving Watson-Crick hydrogen bonding to its target RNA. A specific antisense agent directed against a cell cycle-associated gene mRNA may be useful as a therapeutic in diseases characterized by excess cell proliferation, such as restenosis following balloon angioplasty or cancer.
Solution structure of BmKTX, a K+ blocker toxin from the Chinese scorpionButhus Martensi (2000)

BmKTX is a toxin recently purified from the venom of Buthus Martensi, which belongs to the kaliotoxin family. We have determined its solution structure by use of conventional two-dimensional NMR techniques followed by distance-geometry and energy minimization. The calculated structure is composed of a short alpha-helix (residues 14 to 20) connected by a tight turn to a two-stranded antiparallel beta-sheet (sequences 25-27 and 32-34). The beta-turn connecting these strands belongs to type I. The N-terminal segment (sequence 1 to 8) runs parallel to the beta-sheet although it cannot be considered as a third strand. Comparison of the conformation of BmKTX and toxins of the kaliotoxin family clearly demonstrates that they are highly related. Therefore, analysis of the residues belonging to the interacting surface of those toxins allows us to propose a functional map of BmKTX slightly different from the one of KTX and AgTX2, which may explain the variations in affinities of these toxins towards the Kv1.3 channels.
Density functional modelling in multiphase compositional hydrodynamics (2010)

Abstract This work is essentially a review of a density functional approach in multiphase hydrodynamics developed by the authors during the last 15 years [Dinariev, J Appl Math Mech 1995;59(5):745–752; Dinariev, J Appl Math Mech 1998;62(3):397–405; Demyanov and Dinariev, Fluid Dynam 2004;39(6):933–944; Demianov et al., “Basics of the Density Functional Theory in Hydrodynamics,” Fizmatlit, Moscow; 2009 (in Russian); Dinariev and Evseev, Fluid Dynam 2010;45(1):85–95]. The basic assumption is a representation of the entropy or the Helmholtz energy of the mixture as a functional that is dependent upon chemical component densities. The hydrodynamic system of equations (local conservation laws for chemical components, momentum, and energy) is used to describe multiphase processes, and the constitutive relations (expressions for stresses, diffusion, and heat fluxes) are derived from entropy growth requirement. The authors present the results of numerical simulations describing static and dynamic multiphase systems.
A novel translational repressor mRNA is edited extensively in livers containing tumors caused by the transgene expression of the apoB mRNA-editing enzyme. (1997)

Transgene expression of the apolipoprotein B mRNA-editing enzyme (APOBEC-1) causes dysplasia and carcinoma in mouse and rabbit livers. Using a modified differential display technique, we identified a novel mRNA (NAT1 for novel APOBEC-1 target no. 1) that is extensively edited at multiple sites in these livers. The aberrant editing alters encoded amino acids, creates stop codons, and results in markedly reduced levels of the NAT1 protein in transgenic mouse livers. NAT1 is expressed ubiquitously and is extraordinarily conserved among species. It has homology to the carboxy-terminal portion of the eukaryotic translation initiation factor (eIF) 4G that binds eIF4A and eIF4E to form eIF4F. NAT1 binds eIF4A but not eIF4E and inhibits both cap-dependent and cap-independent translation. NAT1 is likely to be a fundamental translational repressor, and its aberrant editing could contribute to the potent oncogenesis induced by overexpression of APOBEC-1.
Wall conditioning experiments on TFTR using impurity pellet injection (1993)

This work describes experiments intended to optimize the limiter conditioning for TFTR supershots. It is shown that deposition of thin layers of lithium on the limiters by impurity pellet injection changes the plasma-wall interaction and improves supershot performance. Series of up to ten Ohmic plasmas each with two lithium pellets were useful in preconditioning the limiter. Generally, plasma performance increased with the amount of lithium deposited up to the maximal amount which could be deposited. Experiments were performed with different materials being deposited (carbon, boron and lithium) and with different methods of deposition.
Cancer vaccines and immunotherapy. (2002)

It is now clear that many human tumour antigens can be recognised by the immune system. These tumour antigens can be classified into several groups including cancer-testis, differentiation, tissue specific, over-expressed, and viral-associated antigens. In many cases, there is a known molecular basis of carcinogenesis which provides the explanation for the differentiated expression of these antigens in tumours compared with normal cells. Improved understanding of the biology of the immune response, particularly of immune recognition and activation of T-cells, allow better design of vaccines. Pre-clinical comparative studies allow evaluation of optimal vaccine strategies which can then be delivered to the clinic. Currently, a range of cancer vaccines are being tested including those using tumour cells, proteins, peptides, viral vectors, DNA or dendritic cells. Ultimately, this research should give rise to an entirely new modality of cancer treatments.
'Santa Bárbara' and "La casa de Bernarda Alba" (1970)

A characteristic feature of Lorca's poetry and drama is his frequent use of popular material: lullabies and children's songs, popular rhymes and superstitions, ballads and cante jondo. Sometimes th...
Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. (1987)

Gram-negative septicemia elicits multiple abnormalities of the coagulation system. Although products of coagulation can lead to clot formation, thereby potentiating organ damage, recent work has shown that low concentrations of thrombin can protect animals from the shock state. Because these amounts of thrombin also lead to formation in vivo of the anticoagulant enzyme, activated protein C, we examined the role of protein C in modulation of Escherichia coli shock in baboons. First, we infused activated protein C and lethal concentrations of E. coli organisms, which prevented the coagulopathic, hepatotoxic, and lethal effects of E. coli. Second, using an antibody to protein C we blocked protein C activation in vivo to determine if this influenced the response to lethal and sublethal concentrations of E. coli organisms. Under these conditions the response to lethal concentrations of E. coli organisms was made more severe and the response to sublethal concentrations of E. coli was made lethal. The coagulopathic, hepatotoxic, and lethal responses in this latter case were prevented by infusion of exogenous protein C.
4H-SiC Epitaxial Growth on SiC Substrates with Various Off-Angles (2005)

Chemical vapor deposition of 4H-SiC on (0001) substrates with various off-angles from 1o to 45o has been investigated. On large-off-angled (15o-45o) substrates, very smooth surface morphology is obtained in the wide range of C/Si ratio. The micropipe dissociation during epitaxial growth is observed on 4o-45o off-angled substrates with a low C/Si ratio. The incorporation of nitrogen was dramatically suppressed by increasing C/Si ratio irrespective of substrate’s off-angle.
Using a knowledge graph and query click logs for unsupervised learning of relation detection (2013)

In this paper, we introduce a novel statistical language understanding paradigm inspired by the emerging semantic web: Instead of building models for the target application, we propose relying on the semantic space already defined and populated in the knowledge graph for the target domain. As a first step towards this direction, we present unsupervised methods for training relation detection models exploiting the semantic knowledge graphs of the semantic web. The detected relations are used to mine natural language queries against a back-end knowledge base. For each relation, we leverage the complete set of entities that are connected to each other in the graph with the specific relation, and search these entity pairs on the web. We use the snippets that the search engine returns to create natural language examples that can be used as the training data for each relation. We further refine the annotations of these examples using the knowledge graph itself and iterate using a bootstrap approach. Furthermore, we explot the URLs returned for these pairs by the search engine to mine additional examples from the search engine query click logs. In our experiments, we show that, we can achieve relation detection models that perform about 60% macro F-measure on the relations that are in the knowledge graph without any manual labeling, resulting in a comparable performance with supervised training.
Autoinducer production and quorum-sensing dependent phenotypes of Pseudomonas aeruginosa vary according to isolation site during colonization of intubated patients (2007)

Our findings demonstrate that autoinducers are produced during the colonization of intubated patients by P. aeruginosa. The microenvironment, in which P. aeruginosa grows, may select for bacteria with different capacities to produce autoinducers and certain QS-dependent phenotypes. QS-inhibition might therefore affect differently isolates growing inside the biofilm covering intubation devices and those resident in the lungs.
Potent, Selective, and Orally Bioavailable Inhibitors of VPS34 Provide Chemical Tools to Modulate Autophagy in Vivo (2015)

Autophagy is a dynamic process that regulates lysosomal-dependent degradation of cellular components. Until recently the study of autophagy has been hampered by the lack of reliable pharmacological tools, but selective inhibitors are now available to modulate the PI 3-kinase VPS34, which is required for autophagy. Here we describe the discovery of potent and selective VPS34 inhibitors, their pharmacokinetic (PK) properties, and ability to inhibit autophagy in cellular and mouse models.