gebhart/patrepeval huggingface dataset:
Structure-Based, Rational Design of T Cell Receptors (2013)

Adoptive cell transfer using engineered T cells is emerging as a promising treatment for metastatic melanoma. Such an approach allows one to introduce T cell receptor (TCR) modifications that, while maintaining the specificity for the targeted antigen, can enhance the binding and kinetic parameters for the interaction with peptides (p) bound to major histocompatibility complexes (MHC). Using the well-characterized 2C TCR/SIYR/H-2K(b) structure as a model system, we demonstrated that a binding free energy decomposition based on the MM-GBSA approach provides a detailed and reliable description of the TCR/pMHC interactions at the structural and thermodynamic levels. Starting from this result, we developed a new structure-based approach, to rationally design new TCR sequences, and applied it to the BC1 TCR targeting the HLA-A2 restricted NY-ESO-1157-165 cancer-testis epitope. Fifty-four percent of the designed sequence replacements exhibited improved pMHC binding as compared to the native TCR, with up to 150-fold increase in affinity, while preserving specificity. Genetically engineered CD8(+) T cells expressing these modified TCRs showed an improved functional activity compared to those expressing BC1 TCR. We measured maximum levels of activities for TCRs within the upper limit of natural affinity, K D = ∼1 - 5 μM. Beyond the affinity threshold at K D < 1 μM we observed an attenuation in cellular function, in line with the "half-life" model of T cell activation. Our computer-aided protein-engineering approach requires the 3D-structure of the TCR-pMHC complex of interest, which can be obtained from X-ray crystallography. We have also developed a homology modeling-based approach, TCRep 3D, to obtain accurate structural models of any TCR-pMHC complexes when experimental data is not available. Since the accuracy of the models depends on the prediction of the TCR orientation over pMHC, we have complemented the approach with a simplified rigid method to predict this orientation and successfully assessed it using all non-redundant TCR-pMHC crystal structures available. These methods potentially extend the use of our TCR engineering method to entire TCR repertoires for which no X-ray structure is available. We have also performed a steered molecular dynamics study of the unbinding of the TCR-pMHC complex to get a better understanding of how TCRs interact with pMHCs. This entire rational TCR design pipeline is now being used to produce rationally optimized TCRs for adoptive cell therapies of stage IV melanoma.
Mediators of induced pluripotency and their role in cancer cells – current scientific knowledge and future perspectives (2012)

The discovery that overexpression of the transcription factors Oct4, Sox2, Klf4 and c-Myc reprograms differentiated cells into "induced pluripotent stem cells" (iPSCs) has extended our understanding of mechanisms required to maintain stem cell pluripotency and to drive differentiation. Subsequently, additional factors have been discovered that are able to induce a pluripotent state. Recently several groups have succeeded in reprogramming cancer cells to iPSC-like induced pluripotent cancer cells by use of the method established for the generation of iPSCs. This discovery highlighted several striking similarities between pluripotent stem cells and cancer cells, in turn implying that tumorigenesis and reprogramming are partly promoted by overlapping mechanisms. Thus, research on reprogramming might help unravel the mechanisms of carcinogenesis, and vice versa. This review gives an overview of the common features of pluripotent stem cells and cancer cells and summarizes the present state of knowledge in the field of cancer cell reprogramming.
Interaction site of Escherichia coli cyclic AMP receptor protein on DNA of galactose operon promoters. (1979)

Cyclic AMP (cAMP) and its receptor protein (CRP) have a dual role in the regulation of the two promoters that control the galactose (gal) operon of Escherichia coli. One promoter, P1, requires cAMP-CRP for activity; the other, P2, is inhibited by these factors. We have examined the interactions site of cAMP-CRP on gal DNA by using two types of protection experiments, involving DNase digestion and methylation by dimethyl sulfate. Our results indicate that cAMP-CRP binds to gal DNA in a segment located between 50 and 24 base pairs preceding the P1 start point for transcription. Although the location of the cAMP-CRP interaction site is clearly different in gal and lac DNA, comparison of the DNA sequences suggests a similar recognition sequence. The location of the cAMP . CRP-binding site in gal further suggests that protein-protein interactions between RNA polymerase and cAMP . CRP play an important role in transcription initiation at the gal and possibly other cAMP-dependent promoters.
WFST Enabled Solutions to ASR Problems: Beyond HMM Decoding (2011)

During the last decade, weighted finite-state transducers (WFSTs) have become popular in speech recognition. While their main field of application remains hidden Markov model (HMM) decoding, the WFST framework is now also seen as a brick in solutions to many other central problems in automatic speech recognition (ASR). These solutions are less known, and this work aims at giving an overview of the applications of WFSTs in large-vocabulary continuous speech recognition (LVCSR) besides HMM decoding: discriminative acoustic model training, Bayes risk decoding, and system combination. The application of the WFST framework has a big practical impact: we show how the framework helps to structure problems, to develop generic solutions, and to delegate complex computations to WFST toolkits. In this paper, we review the literature, discuss existing approaches, and provide new insights into WFST enabled solutions. We also present a novel, purely WFST-based algorithm for computing the exact Bayes risk hypothesis from a lattice with the Levenshtein distance as loss function. We present the problems and their solutions in a unified framework and discuss the advantages and limits of using WFSTs. We do not provide new experimental results, but refer to the existing literature. Our work helps to identify where and how the transducer framework can contribute to a compact and generic solution to LVCSR problems.
Molecular Markers and Selection for Complex Traits in Plants: Learning from the Last 20 Years (2008)

In the mid‐1980s, the development of abundant molecular markers, appropriate statistical procedures, and user‐friendly computer software that implemented these statistical procedures permitted the detection of molecular markers associated with quantitative trait loci (QTL) for complex traits. Marker‐assisted selection was then proposed as a means of exploiting markers linked to QTL to develop improved cultivars. But while thousands of marker‐trait associations have been reported for many traits in different plant species, far fewer examples of successfully exploiting mapped QTL have been reported in the literature. Key lessons learned from applying markers in plant breeding include the following: (i) the purpose of detecting QTL should be clearly defined before embarking on QTL mapping; (ii) procedures for marker‐based selection depend on the number of QTL; (iii) estimates of QTL effects for complex traits are often inconsistent; and (iv) gain per unit cost and time rather than gain per cycle should be considered. Future applications for complex traits will likely focus on predictive methodologies for marker‐based selection before phenotyping and for marker‐based selection without QTL mapping. These applications will take advantage of cheaper costs of genotyping than of phenotyping.
Dangling-wire avoidance routing for crossbar switch structured ASIC design style (2010)

In the routing architecture of a structured ASIC, crossbar is one of the most area efficient switch blocks. Nevertheless, dangling-wire occurs when there is a routing bend in crossbar switch. The dangling-wire incurs longer wire length as well as higher interconnection capacitance. In this paper, we are motivated to tackle dangling-wire routing issues for structured ASIC. We first propose a compact graph model for crossbar switch routing. With our graph model, switch connectivity relations can be removed to keep the 2-D structured ASIC routing graph efficient and to speed up run-time of our routing algorithm. Furthermore, we leverage state-of-the-art techniques into our routing framework, which contains deferred pin assignment, Steiner point re-assignment, and anchor pair insertion, to minimize dangling-wires taking both total wire length and routing congestion into account. The experimental results demonstrate that our proposed routing framework greatly reduces 21% dangling-wires, 34% channel width, and 13% total wire length as compared with VPR using crossbar switch.
Genetic manipulation of fungal strains for the improvement of heterologous genes expression (a mini-review) (2011)

Fungi are eukaryotic microorganisms that influence our everyday lives in areas as diverse as agriculture, medicine and basic science. With the advent of molecular biology, it has been attempted to improve the expression level of heterologous genes, which encode favorable traits in fungal strains. The expression of heterologous genes can be limited in transcription, post-transcription, translation and post-translation levels. Several genetic strategies have been developed to reduce the expression constrains and to enhance genes functionality. Among these strategies can be pointed to the introduction of multicopies of the desired gene, change of AT-rich sequences, gene fusion with a well-expressed gene, the use of strong promoters and signal sequences, optimization of codon usage, the construction and use of protease-deficient and chaperones/foldases-overproduced  strains and the use of native or artificial intron-containing genes. These strategies have often resulted in the expected increase in the expression of heterologus genes.  With the isolation of a large number of genes encoding desired traits and the availability of a large collection of wild isolates, the improvement of strains with a better functional performance would be possible.   Key words: Strain improvement, gene, heterologous, intron, promoter, codon.
Quantum Phase Transition in Organic Charge-Transfer Complexes (2003)

A phase transition in an organic charge-transfer complex, which originates from the neutral-ionic valence instability, can be tuned toward zero kelvin with use of external pressure or chemical modification as a control parameter. The phase diagram and observed dielectric behaviors are typical of quantum paraelectricity, yet this zero-kelvin transition point namely, the quantum critical point, accompanies large quantum fluctuation of the molecular charge, as demonstrated by the molecular vibrational mode spectra. The result indicates that the pi-electron transfer between donor and acceptor molecules is coupled with the zero-point lattice dynamics around the quantum critical point.
Real-Time Monitoring of Millimeter-Tall Vertically Aligned Single-Walled Carbon Nanotube Growth on Combinatorial Catalyst Library (2010)

The rapid growth dynamics of millimeter-tall, vertically aligned single-walled carbon nanotubes (VA-SWCNTs) was studied using a simple real-time monitoring method. By using combinatorial catalyst libraries, VA-SWCNT growth curves under various catalyst conditions were obtained in a single chemical vapor deposition (CVD) run. VA-SWCNTs grew at constant or gradually decreasing rates for several minutes and then abruptly ceased growth. This unusual behavior of the growth occurred under wide ranges of catalyst and CVD conditions.
Detection of Circulating Parasite Antigen in Murine Fascioliasis by Two-Site Enzyme-Linked Immunosorbent Assays (1989)

A 2-site enzyme immunoassay was developed for the detection of Fasciola hepatica antigen in the serum of fascioliasis infected mice. The assay utilizes high titer rabbit immunoglobulins to parasite excretory/secretory antigens (FhES) as capture antibody, and also as detection antibody when linked to horseradish peroxidase (HRP) or to biotin for reaction with avidin-peroxidase. The assays were compared with a conventional (antibody detection) ELISA to determine diagnostic utility. Using mean rates of detection of fascioliasis, the HRP-based antigen capture assay diagnosed the infection at 1 week postinfection and showed that circulating antigen levels are maximal 3 weeks after infection. The earliest mean diagnosis for the antibody detection and the biotin-based antigen capture ELISAs were 2 and 3 weeks postinfection, respectively. The addition of known quantities of FhES antigens to normal mouse serum gave estimates of lower limits of detectability for the HRP- and biotin-based assays of 25 ng and 0.25 ng, respectively. Routine use of the biotin-avidin system in the antigen capture test resulted in high background activity making this method insensitive.
Effects of fructose on hepatic glucose metabolism (2003)

Fructose is a potent acute regulator of liver glucose uptake and glycogen synthesis. Inclusion of catalytic quantities of fructose in a carbohydrate meal improves glucose tolerance. This improvement is primarily mediated by the activation of hepatic glucokinase and consequent facilitation of liver glucose uptake. The improvement in glucose tolerance is most evident in insulin resistant settings (e.g. Type 2 diabetes and infection). The beneficial effect of fructose on hepatic glucose disposal, however, does not persist if fructose is given continuously such as in total parenteral nutrition.
Transcriptional Regulation of the Mouse Gene Encoding the α-4 Subunit of the GABAA Receptor (2004)

The gamma-aminobutyric acid type A receptors (GABAA-Rs) mediate fast inhibitory synaptic transmission in the brain. The alpha4 subunit of the GABAA-R confers distinct pharmacological properties on the receptor and its expression pattern exhibits plasticity in response to physiological and pharmacological stimuli, including withdrawal from progesterone and alcohol. We have analyzed the promoter region of the mouse GABRA4 gene that encodes the alpha4 subunit and found that the promoter has multiple transcriptional initiation sites and lacks a TATA box. The minimal promoter for GABRA4 spans the region between -444 to -19 bp relative to the coding ATG and shows high activity in cultured mouse cortical neurons. Both Sp3 and Sp4 transcription factors can interact with the two Sp1 binding sites within the minimal promoter and are critical for maximal activity of the promoter in neurons.
Frequency-dependent and frequency-independent nonlinear characteristics of a high-speed laser diode (2003)

It was experimentally demonstrated that a laser diode (LD) can be treated as a memoryless nonlinear device. It was found that for an operating condition with modulation depth below about 60%, the relative time delay (which ranges from zero to several hundred picoseconds) caused by increased modulation depth has a strong effect on the frequency-dependent intermodulation products. In this case, the radiofrequency bandwidth over which the LD can be considered to be effectively memoryless has to be smaller than the inverse of the measured time delay, by two order of magnitude. Increased optical reflections from fiber connectors were observed to cause significant fluctuations of the measured time delay as a function of frequency and thus cause more pronounced frequency-dependent nonlinear behavior. A high speed InGaAsP LD with a threshold current of 15 mA and a 3 dB bandwidth of 6 GHz was used in the experiment.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
The Soluble Guanylyl Cyclase Activator Bay 58-2667 Selectively Limits Cardiomyocyte Hypertrophy (2012)

Our results demonstrate that BAY 58-2667 elicits protective, cardiomyocyte-selective effects in vitro. These actions are associated with sGC activation and are evident in the absence of confounding hemodynamic factors, at low (submicromolar) concentrations. Thus this distinctive sGC ligand may potentially represent an alternative therapeutic approach for limiting myocardial hypertrophy.
Techniques for the translation of MATLAB programs into Fortran 90 (1999)

This article describes the main techiques developed for FALCON's MATLAB-to-Fortran 90 compiler. FALCON is a programming environment for the development of high-performance scientific programs. It combines static and dynamic inference methods to translate MATLAB programs into Fortran 90. The static inference is supported with advanced value propagation techniques and symbolic algorithms for subscript analysis. Experiments show that FALCON's MATLAB translator can generate code that performs more than 1000 times faster than the interpreted version of MATLAB and substantially faster than commercially available MATLAB compilers on one processor of an SGI Power Challenge. Futhermore, in most cases we have tested, the compiler-generated code is as fast as corresponding hand-written programs.
Holographic light deflection (1978)

An operational holographic laser light deflector is described, which is well suited for applications requiring fast constant-speed scanning, high resolution, and moderately large angles of deflection. A particularly unique application of this device as an opaque document scanner is also described.
Micropost array for force mapping of vascular smooth muscle cells (2010)

This paper describes the design, fabrication and characterization of micromachined arrays of 3 dimensional microposts with high aspect ratio and high density made of polydimethylsiloxane (PDMS) flexible material. The arrays are for use to measure quantitatively the cellular traction forces generated by vascular smooth muscle cells (VSMCs) and cells with weaker traction forces (pN-nN range). The fabrication steps were modified to ensure the construction of microposts with diameter and height of 3μm and 30μm, respectively, or aspect ratio up to 10, which has not been reported before. We also report detailed statistical measurements of Young's Modulus and spring constant of PDMS posts using Atomic Force Microscope (AFM) for calibration of each post-geometry used in the cell force measuring experiments. This ensured a higher degree of accuracy of the cell traction force measurements. To demonstrate the sensitivity of the high aspect ratio micropost, VSMCs were cultured on top of micropost array and the traction force maps were generated.
From Somatostatin to Sandostatin®: History and Chemistry (1993)

Abstract The events leading up to the synthesis, pharmacological characterization, development, and marketing of Sandostatin ® (octreotide, SMS 201-995), a potent and long-acting analogue of somatostatin, are briefly reviewed.
Solubility of Potassium Hydroxide and Potassium Phosphate in Supercritical Water (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolubility of Potassium Hydroxide and Potassium Phosphate in Supercritical WaterWilliam T. Wofford and Earnest F. GloynaCite this: J. Chem. Eng. Data 1995, 40, 4, 968–973Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/je00020a052https://doi.org/10.1021/je00020a052research-articleACS PublicationsRequest reuse permissionsArticle Views1176Altmetric-Citations60LEARN 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
Functional interaction of nuclear factors EF-C, HNF-4, and RXR alpha with hepatitis B virus enhancer I (1993)

Hepatitis B virus (HBV) enhancer I contains cis-acting elements that are both sufficient and essential for liver-specific enhancer function. The EF-C binding site was previously shown to be a key element in enhancer I. EF-C binding activity is evident in hepatic and nonhepatic cells. Although the EF-C binding site is required for efficient HBV enhancer I function, the EF-C site does not possess intrinsic enhancer activity when assayed in the absence of flanking elements. We have defined a novel region in HBV enhancer I, termed the GB element, that is adjacent to and functions in conjunction with the EF-C binding site. The GB element and EF-C site confer interdependent liver-specific enhancer activity in the absence of flanking HBV enhancer sequences. The nucleotide sequence of the GB element is similar to sequences of the DNA binding sites for members of the steroid receptor superfamily. Among these proteins, we demonstrate that HNF-4, RXR (retinoid X receptor), and COUP-TF bind to the GB element in vitro. HNF-4 transactivates a promoter linked to a multimerized GB/EF-C domain via the GB element in vivo in a manner that is dependent on the integrity of the adjacent EF-C binding site. RXR alpha also transactivates promoter expression via the GB element in vivo in response to retinoic acid but in a largely EF-C-independent manner. Finally, we show that COUP-TF antagonizes the activity of the GB element in human liver cells.
Mixed Surfactant Bilayers on Monodispersed Ferric Hydro Sols (1988)

Abstract The properties of mixed surfactant bilayers on monodispersed ferric hydro sol were studied by measuring the amount of surfactant adsorbed, particle size, and pyrene fluorescence spectra. The positively charged sols flocculated upon addition of sodium dodecyl sulfate (SDS) or lithium perfluoro-1-octanesulfonate (LiFOS) were redispersed by further addition of poly(oxyethylene) nonyl phenyl ether (NP7.5) due to the formation of a mixed surfactant bilayer on the sols. The mixed surfactant bilayer of SDS–NP7.5 on the sols was more easily formed than LiFOS–NP7.5. Fluorescence fine structure of pyrene gave information on the polarity of the microenvironment in the mixed surfactant layer on the sols.
Analysis, Analysis Practices, and Implications for Modeling and Simulation (2007)

This paper addresses analysis and analysis practices for defense planning and their implications for modeling and simulation (M&S). The analysis in question is accomplished for Quadrennial Reviews and for continuing work on capability assessments, requirements analysis, and program analysis. The paper's purpose is to delineate priorities for the way ahead i.e., for investments and other actions to ensure that future M&S will serve the needs of defense planning analysis. Traditionally, analysis for defense planning has been at the strategic and operational levels, but what these levels now include is unclear, given that the organization of forces is changing, low-level activities can have strategic importance, and sound assessment of capabilities sometimes requires in-depth analysis. Accordingly, the paper takes a broad view of its scope, although not adequately addressing some issues (notably related to systems of systems [SoS], personnel, training, and operations planning) that are usually seen as subjects for other communities. Future work should address the substantial overlaps that increasingly exist across the M&S-using communities.