gebhart/patrepeval huggingface dataset:
Organization of proximal signal initiation at the TCR:CD3 complex (2009)

The series of events leading to T-cell activation following antigen recognition has been extensively investigated. Although the exact mechanisms of ligand binding and transmission of this extracellular interaction into a productive intracellular signaling sequence remains incomplete, it has been known for many years that the immunoreceptor tyrosine activation motifs (ITAMs) of the T-cell receptor (TCR):CD3 complex are required for initiation of this signaling cascade because of the recruitment and activation of multiple protein tyrosine kinases, signaling intermediates, and adapter molecules. It however remains unclear why the TCR:CD3 complex requires 10 ITAMs, while many other ITAM-containing immune receptors, such as Fc receptors (FcRs) and the B cell receptor (BCR), contain far fewer ITAMs. We have recently demonstrated that various parameters of T cell development and activation are influenced by the number, as well as location and type, of ITAMs within the TCR:CD3 complex and hence propose that the TCR is capable of 'scalable signaling' that facilitates the initiation and orchestration of diverse T-cell functions. While many of the underlying mechanisms remain hypothetical, this review intends to amalgamate what we have learned from conventional biochemical analyses regarding initiation and diversification of T-cell signaling, with more recent evidence from molecular and fluorescent microscopic analyses, to propose a broader purpose for the TCR:CD3 ITAMs. Rather than simply signal initiation, individual ITAMs may also be responsible for the differential recruitment of signaling and regulatory molecules which ultimately affects T-cell development, activation and differentiation.
Transducer design for a portable ultrasound enhanced transdermal drug-delivery system (2002)

For application in a portable transdermal drug-delivery system, novel transducers have been designed to enhance insulin transmission across skin using ultrasound. Previous research has shown transdermal delivery of insulin across skin using commercial sonicators operating at 20 kHz with intensities ranging from 12.5 to 225 mW/cm2. The goal of this research was to design and construct a small, lightweight transducer or array that could operate with a similar frequency and intensity range as a commercial sonicator used in previous transdermal ultrasound insulin experiments, but without the weight and mass of a sonicator probe. To obtain this intensity range, a cymbal transducer design was chosen because of its light, compact structure and low resonance frequency in water. To increase the spatial ultrasound field for drug delivery across skin, two arrays, each comprising of four cymbal transducers, were constructed. The first array, designated the standard array, used four cymbals transducer elements in parallel. A second array (named the stack array) used four cymbal transducers that used stacked piezoelectric discs to drive the titanium flextensional caps. Under similar driving conditions, the standard array produced intensities comparable to those achieved using a commercial sonicator.
Demonstrating the C‐terminal boundary of the HIV 1 fusion conformation in a dynamic ongoing fusion process and implication for fusion inhibition (2007)

The core complex is a structure involved in the fusion mechanism of many viruses, as well as in intracellular vesicle fusion. A powerful approach for studying the dynamic stages of HIV-1-cell fusion utilizes DP178, a core complex inhibitory peptide derived from the known sequence of the virus. Strikingly, we show that fatty acids can replace the entire C-terminal region of DP178, known to play a crucial role in the activity of the peptide. The inhibitory activity correlated with the length of the fatty acid, with the direction of fatty acid attachment (N- or C-terminus) and, as envisioned by a new triple staining assay, with the concentration of the peptides on cells. Our findings indicate, for the first time, the C-terminal boundary of the endogenous core structure in situ and establish that the C-terminal region of DP178 functions mainly as an anchor to the cell membrane. Apart from the mechanistic implications, such short lipopeptides provide new, promising fusion inhibitors. Because the fusion mechanism of HIV-1 is shared by other pathogen-enveloped viruses and by intracellular vesicle fusion, our results might influence the research and therapeutic efforts in these systems as well.
Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90 (1996)

The role of the abundant stress protein Hsp90 in protecting cells against stress-induced damage is not well understood. The recent discovery that a class of ansamycin antibiotics bind specifically to Hsp90 allowed us to address this problem from a new angle. We find that mammalian Hsp90, in cooperation with Hsp70, p60, and other factors, mediates the ATP-dependent refolding of heat-denatured proteins, such as firefly luciferase. Failure to refold results in proteolysis. The ansamycins inhibit refolding, both in vivo and in a cell extract, by preventing normal dissociation of Hsp90 from luciferase, causing its enhanced degradation. This mechanism also explains the ansamycin-induced proteolysis of several protooncogenic protein kinases, such as Raf-1, which interact with Hsp90. We propose that Hsp90 is part of a quality control system that facilitates protein refolding or degradation during recovery from stress. This function is used by a limited set of signal transduction molecules for their folding and regulation under nonstress conditions. The ansamycins shift the mode of Hsp90 from refolding to degradation, and this effect is probably amplified for specific Hsp90 substrates.
Extensible file system (ELFS) (1994)

Scientific applications often manipulate very large sets of persistent data. Over the past decade, advances in disk storage device performance have consistently been outpaced by advances in the performance of the rest of the computer system. As a result, many scientific applications have become I/O-bound, i.e. their run-times are dominated by the time spent performing I/O operations. Consequently, the performance of I/O operations has become critical for high performance in these applications. The ELFS approach is designed to address the issue of high performance I/O by treating files as typed objects. Typed file objects can exploit knowledge about the file structure and type of data. Typed file objects can selectively apply techniques such as prefetching, parallel asynchronous file access, and caching to improve performance. Also, by typing objects, the interface to the user can be improved in two ways. First, the interface can be made easier to use by presenting file operations in a more natural manner to the user. Second, the interface can allow the user to provide an “oracle” about access patterns, that can allow the file object to improve performance. By combining these concepts with the object-oriented paradigm, the goal of the ELFS methodology is to create flexible, extensible file classes that are easy to use while achieving high performance. In this paper we present the ELFS approach and our experiences with the design and implementation of two file classes: a two dimensional dense matrix file class and a multidimensional range searching file class.
End-to-End Deep Learning for Steering Autonomous Vehicles Considering Temporal Dependencies (2017)

Steering a car through traffic is a complex task that is difficult to cast into algorithms. Therefore, researchers turn to training artificial neural networks from front-facing camera data stream along with the associated steering angles. Nevertheless, most existing solutions consider only the visual camera frames as input, thus ignoring the temporal relationship between frames. In this work, we propose a Convolutional Long Short-Term Memory Recurrent Neural Network (C-LSTM), that is end-to-end trainable, to learn both visual and dynamic temporal dependencies of driving. Additionally, We introduce posing the steering angle regression problem as classification while imposing a spatial relationship between the output layer neurons. Such method is based on learning a sinusoidal function that encodes steering angles. To train and validate our proposed methods, we used the publicly available Comma.ai dataset. Our solution improved steering root mean square error by 35% over recent methods, and led to a more stable steering by 87%.
Fluorescent lifetimes of molecules on silver-island films (1982)

The fluorescence of molecules on silver-island films exhibits nonexponential decay and is several orders of magnitude more rapid than on a silica surface, while the total emission intensity is slightly increased. This behavior results from the electromagnetic coupling between the fluorescing molecules and the plasmon resonances of the silver islands. We obtain good agreement with a model that uses the same theory for the electromagnetic coupling as has been used to account for surface-enhanced Raman scattering.
Controlling ammonia losses during manure composting with the addition of phosphogypsum and simple superphosphate (1995)

With the purpose of evaluating the effectiveness of phosphogypsum and simple superphosphate in controlling ammonia losses by volatilization during the process of manure composting, an experiment was carried out in closed flasks of 1.6 liter, in which different rates (50, 100, 150 and 200 kg.t-1) of phosphogypsum and simple superphosphate were mixed with a substrate composed of equal amounts (on weight basis) of fresh chicken manure and cattle manure. Ammonia lost by volatilization was determined after 7, 14, 21, 28 and 35 days by trapping the gas in sulfuric acid solution placed in a small glass vial which, in turn, was maintained inside the volatilization flask The remaining acid after the exposure to ammonia was determined by titration with 0.025N NaOH. The amount of ammonia lost by volatilization from the samples decreased with the addition of both products, but for all rates applied, phosphogypsum was more efficient than simple superphosphate. The reduction in volatilization increased with the rate of application of both additives. There was an evidence that the reduction of ammonia loss was due to the presence of gypsum in the additives.
Isolation of a mutant from Salmonella typhimurium producing acyl‐deficient lipopolysaccharides (1988)

The present paper describes the isolation and characterization of a mutant (mutant Ts7) of Salmonella typhimurium that is conditionally defective in the incorporation of dodecanoic and tetradecanoic acid into lipopolysaccharide precursor structures. Enrichment of mutant Ts7 was achieved by free-flow electrophoresis and was based on a previous observation that at least some Salmonella mutants conditionally blocked in the synthesis of the 3-deoxy-D-manno-octulosonic acid (dOc1A)-lipid-A region exhibit higher electrophoretic mobilities than cells with intact dOc1A-lipid-A regions. Under nonpermissive conditions (42 degrees C) mutant Ts7 accumulates at least two incomplete dOc1A-lipid-A structures. One is made up of glucosamine, phosphate, dOc1A, and 3-hydroxytetradecanoic acid in a molar ratio 1.0:1.3:1.0:2.2 and is devoid of dodecanoic and tetradecanoic acid. The other structure has the same basic structure but contains hexadecanoic acid.
Actin-Sequestering Ability of Thymosin β4, Thymosin β4Fragments, and Thymosin β4-Like Peptides as Assessed by the DNase I Inhibition Assay (1993)

Thymosin beta 4 containing 43 amino-acid residues belongs to a family of highly homologous peptides present at high concentrations in various species, cells, and tissues. Safer et al. [J. Biol. Chem. 266, 4029-4032 (1991)] have shown that thymosin beta 4 is an actin-sequestering peptide. Because DNase I is inhibited by G-actin and not by F-actin we employed this enzymatic assay to determine the actin sequestering properties of 4 other thymosin beta 4-like peptides and fragments of thymosin beta 4 generated by enzymatic digestions. Thymosin beta 4 sequesters G-actin at a 1 to 1 ratio an thereby inhibits its polymerisation to F-actin in high salt solution. The oxidation of the single methionine residue at position 6 does not abolish its actin-sequestering properties. However neither thymosin beta 4 24-43 nor thymosin beta 4 13-43 inhibit the polymerisation of G-actin. We conclude from this that some structural features in the amino-acid sequence of thymosin beta 4 before position 13 are obligatory for its biological function. Oxidized thymosin beta 4 (beta 4-sulfoxide) as well as four other thymosin beta 4-like peptides were shown to be actin-sequestering peptides like thymosin beta 4.
The feature selection problem: traditional methods and a new algorithm (1992)

For real-world concept learning problems, feature selection is important to speed up learning and to improve concept quality. We review and analyze past approaches to feature selection and note their strengths and weaknesses. We then introduce and theoretically examine a new algorithm Rellef which selects relevant features using a statistical method. Relief does not depend on heuristics, is accurate even if features interact, and is noise-tolerant. It requires only linear time in the number of given features and the number of training instances, regardless of the target concept complexity. The algorithm also has certain limitations such as nonoptimal feature set size. Ways to overcome the limitations are suggested. We also report the test results of comparison between Relief and other feature selection algorithms. The empirical results support the theoretical analysis, suggesting a practical approach to feature selection for real-world problems.
Towards artificial ribonucleases: the sequence-specific cleavage of RNA in a duplex (1996)

Lanthanide complexes covalently attached to oligonucleotides have been shown to cleave RNA in a sequence-specific manner. Efficient cleavage, however, is at present limited to single-stranded RNA regions, as RNA in a duplex is considerably more resistant to strand scission. To overcome this limitation, we have designed and synthesised artificial nucleases comprising lanthanide complexes covalently linked to oligodeoxyribonucleotides which cleave a partially complementary RNA at a bulged site, in the duplex region. Strand scission occurs at or near the bulge. Cleavage of the RNA target by the metal complex can be addressed via the major or the minor groove. In an example of a competitive situation, where the cleavage moiety has access to both a bulge and a single-strand region, transesterification at the bulge is favoured. Such artificial ribonucleases may find application as antisense agents and as tools in molecular biology. In addition, the results may have importance for the design of artificial ribonucleases which are able to act with catalytic turnover.
Percutaneous mitral valve dilatation with the multi-track system (1999)

We developed the Multi-Track System for percutaneous mitral valvotomy and described the preliminary results in 1995. Here we report the first 100 consecutive cases after the original publication. Two separate balloon catheters are positioned on a single guidewire. The first catheter, with only a distal guidewire lumen, is introduced into the vein and then advanced into the mitral orifice. Subsequently, a rapid exchange balloon catheter running on the same guidewire is inserted and lined up with the first catheter so the two are positioned side by side. Both balloons are then inflated simultaneously. Age of the patients was 31 +/- 12.8 years and weight 50 +/- 14 kg. Valve area increased 0.75 +/- 0.22 cm(2) to 2.00 +/- 0.32 cm(2)and mean left atrial pressure dropped from 27 +/- 8 to 11 +/- 5 mm Hg. One patient had significant mitral insufficiency after dilatation, which did not require surgery. The Multi-Track System is a valid alternative to the existing procedures for the treatment of mitral stenosis and uses simpler and less costly catheters. Cathet. Cardiovasc. Intervent. 48:178-183, 1999.
Synthetic peptide F2A4-K-NS mimics fibroblast growth factor-2 in vitro and is angiogenic in vivo (2006)

A multi-domain synthetic peptide, F2A4-K-NS, mimicked the action of recombinant human FGF-2 (rhFGF-2) in vitro and in an in vivo model of angiogenesis. Like rhFGF-2, F2A4-K-NS was quantitatively shown to bind to FGF receptors in a cell-free receptor binding assay using a chimeric FGFR1 (IIIc)/Fc as monitored by surface plasmon resonance (SPR), and also shown to bind to heparin using biotinylated low-molecular weight heparin in a similar SPR assay. In vitro, F2A4-K-NS triggered signal transduction as monitored by the stimulation of ERK1/2 phosphorylation in human umbilical cord endothelial cells. In cell based assays, it increased cell migration, cell proliferation, and gelatinase secretion; endpoints associated with FGF-2 stimulation. Furthermore, these in vitro effects were mediated with quantities of F2A4-K-NS that were similar to those of rhFGF-2. In vivo, F2A4-K-NS was angiogenic at doses of 40 and 400 ng/implant in a subcutaneous implant assay as determined by morphologic scoring, hemoglobin content, and histology. These results support the hypothesis that F2A4-K-NS is a mimetic of FGF-2 that can substitute for FGF-2 in vitro and in vivo. A synthetic mimetic of FGF-2, such as F2A4-K-NS, could be a useful tool in studying mechanisms of cell activation and potentially in various therapeutic applications.
Cloning and Characterization ofCIS 1b(Cytokine Inducible SH2-Containing Protein lb), an Alternative Splicing Form ofCIS 1Gene (2000)

JAK-STAT pathway is essential in relaying cytokine signals and plays a vital role in cellular responses such as proliferation, differentiation and immunity. Some members of a recently found cytokine-inducible SH2 protein (CIS, =SOCS or SSI) family have proved to have negative effects on modulating JAK-STAT signaling pathway. In the present study, a novel human cDNA (CIS1b) which proved to be a variant of CIS1 gene was isolated by screen human placenta lambda gt11 cDNA library and 5'-rapid amplification of cDNA ends (RACE). Furthermore, the gene structure of CIS1 was determined by comparing the cDNA sequences of CIS1 and CIS1b to the genomic sequence in human chromosome 3p21.3. The expression patterns of CIS1b as well as CIS1 were analysed by Northern blot.
Tetracyclines. 9. Total synthesis of dl-terramycin (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTetracyclines. 9. Total synthesis of dl-terramycinHans Muxfeldt, George Haas, Goetz Hardtmann, Faizulla Kathawala, Jared B. Mooberry, and Edwin VedejsCite this: J. Am. Chem. Soc. 1979, 101, 3, 689–701Publication Date (Print):January 1, 1979Publication History Published online1 May 2002Published inissue 1 January 1979https://pubs.acs.org/doi/10.1021/ja00497a035https://doi.org/10.1021/ja00497a035research-articleACS PublicationsRequest reuse permissionsArticle Views776Altmetric-Citations61LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Membrane phospholipid asymmetry: host response to the externalization of phosphatidylserine (1996)

Membrane phospholipid asymmetry is an important regulator of cellular function and homeostasis. The activities of lipid transporters are contributing factors to the regulation of membrane lipid composition over the lifespan of the cell. Alterations in the activities of these proteins result in the movement of phosphatidylserine to the cell's outer leaflet. This promotes several physiologic responses including initiation of the coagulation cascade and cell recognition by the reticuloendothelial system.
Corneal dystrophies (2009)

The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea. The designation is imprecise but remains in vogue because of its clinical value. Clinically, the corneal dystrophies can be divided into three groups based on the sole or predominant anatomical location of the abnormalities. Some affect primarily the corneal epithelium and its basement membrane or Bowman layer and the superficial corneal stroma (anterior corneal dystrophies), the corneal stroma (stromal corneal dystrophies), or Descemet membrane and the corneal endothelium (posterior corneal dystrophies). Most corneal dystrophies have no systemic manifestations and present with variable shaped corneal opacities in a clear or cloudy cornea and they affect visual acuity to different degrees. Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or X-linked recessive Mendelian mode of inheritance. Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Knowledge about the responsible genetic mutations responsible for these disorders has led to a better understanding of their basic defect and to molecular tests for their precise diagnosis. Genes for other corneal dystrophies have been mapped to specific chromosomal loci, but have not yet been identified. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents. Main differential diagnoses include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic lysosomal storage diseases (mucopolysaccharidoses, lipidoses, mucolipidoses), and several skin diseases (X-linked ichthyosis, keratosis follicularis spinolosa decalvans). The management of the corneal dystrophies varies with the specific disease. Some are treated medically or with methods that excise or ablate the abnormal corneal tissue, such as deep lamellar endothelial keratoplasty (DLEK) and phototherapeutic keratectomy (PTK). Other less debilitating or asymptomatic dystrophies do not warrant treatment. The prognosis varies from minimal effect on the vision to corneal blindness, with marked phenotypic variability.