gebhart/patrepeval huggingface dataset:
Prediction of siRNA functionality using generalized string kernel and support vector machine (2005)

Small interfering RNAs (siRNAs) are becoming widely used for sequence-specific gene silencing in mammalian cells, but designing an effective siRNA is still a challenging task. In this study, we developed an algorithm for predicting siRNA functionality by using generalized string kernel (GSK) combined with support vector machine (SVM). With GSK, siRNA sequences were represented as vectors in a multi-dimensional feature space according to the numbers of subsequences in each siRNA, and subsequently classified with SVM into effective or ineffective siRNAs. We applied this algorithm to published siRNAs, and could classify effective and ineffective siRNAs with 90.6%, 86.2% accuracy, respectively.
Conformational studies on neurohypophyseal hormones: the disulfide bridge of oxytocin. (1968)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Improved high‐affinity monoclonal antibody to lododeoxyuridine (1986)

Three monoclonal antibodies (Mabs), IU-1, IU-4, and B-44 were evaluated in enzyme immunoassays (ELISA) and by flow cytometry for their abilities to recognize bromodeoxyuridine (BrdUrd)- and iododeoxyuridine (IdUrd)-substituted DNA's, nucleotides, and nucleosides. IU-4 is a new Mab, derived from mice immunized with 5-iodo-2'-deoxyuridine-5'-monophosphate (IdUMP) conjugated (IdUMP) conjugated through the phosphate group to albumin. This immunogen was selected to resemble IdUMP in DNA. In competition ELISA assays, IU-4 prefers IdUrd to BrdUrd and prefers halogenated nucleotides over the corresponding nucleosides. In both ELISA and flow analysis, IU-4 recognizes IdUrd in DNA at substitution frequencies at least as low as one IdUrd one per 1,000 normal bases. The high affinity of IU-4 for IdUrd-DNA contrasts with IU-1 and B-44, which show a strong binding dependency on the frequency of base substitution and require DNA that is essentially fully substituted with BrdUrd for binding in both flow and ELISA assays. The high affinity of IU-4 for IdUrd in DNA and its independence of IdUrd residue spacing make it a superior reagent for the quantitative labeling of halogenated thymidine analogues in whole cells.
Prediction of Absolute Solvation Free Energies using Molecular Dynamics Free Energy Perturbation and the OPLS Force Field (2010)

The accurate prediction of protein-ligand binding free energies is a primary objective in computer-aided drug design. The solvation free energy of a small molecule provides a surrogate to the desolvation of the ligand in the thermodynamic process of protein-ligand binding. Here, we use explicit solvent molecular dynamics free energy perturbation to predict the absolute solvation free energies of a set of 239 small molecules, spanning diverse chemical functional groups commonly found in drugs and drug-like molecules. We also compare the performance of absolute solvation free energies obtained using the OPLS_2005 force field with two other commonly used small molecule force fields-general AMBER force field (GAFF) with AM1-BCC charges and CHARMm-MSI with CHelpG charges. Using the OPLS_2005 force field, we obtain high correlation with experimental solvation free energies (R(2) = 0.94) and low average unsigned errors for a majority of the functional groups compared to AM1-BCC/GAFF or CHelpG/CHARMm-MSI. However, OPLS_2005 has errors of over 1.3 kcal/mol for certain classes of polar compounds. We show that predictions on these compound classes can be improved by using a semiempirical charge assignment method with an implicit bond charge correction.
Improvement of flux pinning in the Ag-clad Bi-Pb-Sr-Ca-Cu-O wires through the use of a short period melt processing (1992)

A significant enhancement of the Jc in magnetic field in the Ag-clad Bi-Pb-Sr-Ca-Cu-O (BPSCCO) wires has been achieved by using a short period melt processing. The weak links have been largely eliminated in the melt-processed tapes which exhibits a 3–10-fold increase in the Jc at 77 K and 1 T over the normally processed tapes. For tapes with a thickness 80 μm 60% of melt-processed samples have the Jc values between 10 000 and 27 000 A/cm2 at 77 K in zero field. The irreversibility lines determined using ac susceptibility measurements under dc fields confirmed the improvement of flux pinning in the melt-processed tapes compared with the normally processed tapes. The improved Jc-H characteristics may be attributed to the desirable microstructures produced from the high Tc phase formation-decomposition-recovery process through the use of a short period melting.
ATM in B-ISDN communication systems and VLSI realization (1995)

The Asynchronous Transfer Mode (ATM) is considered to be a key technology for B-ISDN. This paper discusses VLSI trends and how VLSI's can be applied to realize ATM switching node systems for B-ISDN. Implementing a practical ATM node system will require the development of technologies such as high-throughput ATM switch LSI's with up to 10 Gb/s capacity and SDH termination technology based on optical fiber transmission. An ATM traffic-handling mechanism with Quality of Service (QoS) controls such as ATM layer performance monitoring, virtual channel handling, usage parameter control, and VP shaping requires several hundred thousand logic gates and several megabytes of high-speed static RAM; VLSI's must be introduced if such mechanisms are to be implemented. ATM node system architecture is based on design principles of a building-block-type structure and hierarchical multiplexing. The basic ATM call handling module, the AHM, is composed mainly of a line termination block and a self-routing switch block; we analyzed this module from the viewpoint of the amount of hardware it requires. Finally, future ATM node systems are discussed on the basis of 0.2-/spl mu/m VLSI development trends and hardware requirements such as the need for ultrahigh integration of logic gate with memory, multichip modules, and low power dissipation technology.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
CREB-binding Protein Is a Nuclear Integrator of Nuclear Factor-κB and p53 Signaling (1999)

Transcriptional coactivators may function as nuclear integrators by coordinating diverse signaling events. Here we show that the p65 (RelA) component of nuclear factor-kappaB (NF-kappaB) and p53 mutually repress each other's ability to activate transcription. Additionally, tumor necrosis factor-activated NF-kappaB is inhibited by UV light-induced p53. Both p65 and p53 depend upon the coactivator CREB-binding protein (CBP) for maximal activity. Increased levels of the coactivator relieve p53-mediated repression of NF-kappaB activity and p65-mediated repression of p53-dependent gene expression. Nuclear competition for limiting amounts of CBP provides a novel mechanism for altering the balance between the expression of NF-kappaB-dependent proliferation or survival genes and p53-dependent genes involved in cell cycle arrest and apoptosis.
Multichannel wavelength-switched transmitters and receivers-new concepts for broadband networks and distributed switching systems (1990)

Three component concepts for use in high-density wavelength-division-multiplexed optical systems are described. The applications envisaged for these components include broadband overlay for subscriber access networks and ultrahigh-capacity packet switching for telecommunications or parallel processing computer applications. The components each use a dispersive optical grating and integrated array of optoelectronic transducers to form a component with precisely defined multiple operating wavelength channels. Multichannel laser transmitter and direct detection receiver components suitable for up to about 50 independent channels separated by 1-2 nm in the 1300- to 1600-nm-wavelength range are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Structure and History of Yiddish (1993)

Abstract Yiddish was the proud language of the European Jewish communities and their offspring, which can be found scattered throughout the world. It has been observed that Yiddish is a mixture of various elements, both traditional and modern. There are what is termed stock languages, those that are the original form of the language. Determinants are those that have sprung out of the stock languages at any time in history; and finally, components are those that arise from the fusion of the influences of cultural and current events and the language advances through decades. The position of the Jews in the European region exposed them to different traditions and influences. These, with emerging forms of modern writing, have led to the alteration of the literature at various levels.
Vaccinia Topoisomerase Mutants Illuminate Conformational Changes during Closure of the Protein Clamp and Assembly of a Functional Active Site (2001)

We present a mutational analysis of vaccinia topoisomerase that highlights the contributions of five residues in the catalytic domain (Phe-88 and Phe-101 in helix alpha1, Ser-204 in alpha5, and Lys-220 and Asn-228 in alpha6) to the DNA binding and transesterification steps. When augmented by structural information from exemplary type IB topoisomerases and tyrosine recombinases in different functional states, the results suggest how closure of the protein clamp around duplex DNA and assembly of a functional active site might be orchestrated by internal conformational changes in the catalytic domain. Lys-220 is a constituent of the active site, and a positive charge at this position is required for optimal DNA cleavage. Ser-204 and Asn-228 appear not to be directly involved in reaction chemistry at the scissile phosphodiester. We propose that (i) Asn-228 recruits the Tyr-274 nucleophile to the active site by forming a hydrogen bond to the main chain of the tyrosine-containing alpha8 helix and that (ii) contacts between Ser-204 and the DNA backbone upstream of the cleavage site trigger a separate conformational change required for active site assembly. Mutations of Phe-88 and Phe-101 affect DNA binding, most likely at the clamp closure step, which we posit to entail a distortion of helix alpha1.
Subclass approach for mutational spectrum analysis. (1995)

Analysis and comparison of mutational spectra represents a burning question in molecular biology. We report an algorithm based upon the SEM subclass approach (SEM--stochastique, estimations, maximizations). Any real mutational spectrum is regarded as a mixture of standard binomial distributions. The separation procedure is run by rounds. Each iteration includes simulation, maximization and estimation. The algorithm has been checked on random spectra with the preset parameters and on real mutational spectra. As has been shown, any real mutational spectrum can be represented as a mixture of two and more binomial distributions, of which one contains hotspots of mutation.
A 10 Gb/s 4-ary ASK lightwave system (1997)

Simulation and experimental results are presented for an externally-modulated 10 Gb/s 4-ary ASK lightwave system employing optical amplifiers. Transmission results over standard singlemode fiber are presented for distances up to 225 km.
Matrix-Assisted Laser Desorption Ion Trap Mass Spectrometry:  Efficient Trapping and Ejection of Ions (1996)

The present paper explores the coupling of a matrix-assisted laser desorption/ionization (MALDI) ion source with an ion trap mass analyzer, with particular emphasis on the development of methods for improving the efficiency of ion trapping and ejection. A technique is described for directly measuring, for the first time, the trapping efficiency of peptide ions produced in a remote external MALDI ion source. The technique was used to devise an improved scheme for trapping, which yielded efficiencies as high as 39%. An improved understanding of the resonant ejection process led us to a new resonant ejection parameter set that increased the ejection efficiency by 1 order of magnitude over more conventionally used parameter sets and allowed for marked improvements in the mass resolution of ions with m/z > 2500. The presently described improvements in the efficiencies of ion trapping and ejection together with improved methods for isolating and fragmenting ions (Qin, J.; Chait, B.T.Anal. Chem., following article in this tissue) lay the foundation for highly sensitive MALDI ion trap mass spectrometry of proteins (Qin, J.; et al. Anal. Chem. 1996, 68, 1784-1791).
Innate Immunity and the Failing Heart (2015)

Elevated levels of inflammatory mediators have been identified in patients with heart failure, including heart failure with reduced and preserved ejection fraction, as well as acute decompensated heart failure. Moreover, experimental studies have shown repeatedly that activation of inflammation in the heart provokes left ventricular remodeling and left ventricular dysfunction. Nonetheless, phase III clinical trials that have attempted to antagonize inflammatory mediators have been negative with respect to the primary end points of the trials, and in some patients, resulted in worsening heart failure or death. The following review will discuss how recent developments in the field of innate immunity have advanced our understanding of the role of inflammation in the pathogenesis of heart failure and will discuss the negative outcomes of the existing clinical trials in light of this new information.
A Pentaerythritol-Based Molecular Scaffold for Solid-Phase Combinatorial Chemistry (2001)

A convergent synthesis has been developed for the preparation of solid-phase bound construct 1, consisting of an orthogonally protected trifunctional core structure that is attached to TentaGel via a photocleavable linker. [structure: see text]
A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. (1997)

A novel polymorphism in the extracellular domain 2 (EC2) of FcgammaRIIIA affects ligand binding by natural killer (NK) cells and monocytes from genotyped homozygous normal donors independently of receptor expression. The nonconservative T to G substitution at nucleotide 559 predicts a change of phenylalanine (F) to valine (V) at amino acid position 176. Compared with F/F homozygotes, FcgammaRIIIa expressed on NK cells and monocytes in V/V homozygotes bound more IgG1 and IgG3 despite identical levels of receptor expression. In response to a standard aggregated human IgG stimulus, FcgammaRIIIa engagement on NK cells from V/V (high-binding) homozygotes led to a larger rise in [Ca2+]i, a greater level of NK cell activation, and a more rapid induction of activation-induced cell death (by apoptosis). Investigation of an independently phenotyped normal cohort revealed that all donors with a low binding phenotype are F/F homozygotes, while all phenotypic high binding donors have at least one V allele. Initial analysis of 200 patients with SLE indicates a strong association of the low binding phenotype with disease, especially in patients with nephritis who have an underrepresentation of the homozygous high binding phenotype. Thus, the FcgammaRIIIa polymorphism at residue 176 appears to impact directly on human biology, an effect which may extend beyond autoimmune disease characterized by immune complexes to host defense mechanisms.
The Role of Cytokines in Schwann Cell Damage, Protection, and Repair (1997)

Cytokines, proteins that are secreted by many cells, including inflammatory and glial cells, mediate interactions between cells, generally through paracrine and autocrine networks. Their effects are highly pleiotropic, with overlap of some activities. The pathogenesis of Guillain-Barré syndrome (GBS), especially the classic inflammatory demyelinating polyneuropathy form, seems to involve lymphocytes and macrophages, which are rich sources of cytokines. Macrophages likely have a role in the pathogenesis of the primarily axonal, less inflammatory forms of GBS. Cytokines appear to be involved in damage to Schwann cells, myelin, and axons, although the exact roles of the different cytokines is uncertain. There is increasing evidence that cytokines, including some proinflammatory cytokines that ordinarily cause damage, may also protect the cells of the peripheral nervous system and aid in its repair. The evolution of inflammatory and demyelinating disorders, including the degree of recovery, is probably dependent on the interactions of the different cytokines.
Real time processing enables fast 3D imaging at single photon level (2008)

3D LIDAR imaging is a key enabling technology for automatic navigation of future spacecraft, including landing, rendezvous and docking and rover navigation. Landing is typically the most demanding task because of the range of operation, speed of movement, field of view (FOV) and the spatial resolution required. When these parameters are combined with limited mass and power budget, required for interplanetary operations, the technological challenge becomes significant and innovative solutions must be found. Single Photon Avalanche Photodiodes (SPADs) can reduce the laser power by orders of magnitude, array detector format can speed up the data acquisition while some limited scanning may extend the FOV without pressure on the mechanics. In the same time, SPADs have long dead times that complicate their use for rangefinding. Optimization and balance between the instrument subsystems are required. We discuss how the implementation of real-time control as an integral part of the LIDAR allows the use of SPAD array detectors in conditions of high dynamics. The result is a projected performance of more than 1 million 3D pixels/s at a distance of several kilometers within a small mass/power package. The work is related to ESA technology development for future planetary landing missions.
Abstract: Runlength Compression Techniques for FPGA Configurations 1 (1999)

The time it takes to reconfigure FPGAs can be a significant overhead for reconfigurable computing. In this paper we develop new compression algorithms for FPGA configurations that can significantly reduce this overhead. By using runlength and other compression techniques, files can be compressed by a factor of 3.6 times. Bus transfer mechanisms and decompression hardware are also discussed. This results in a single compression methodology which achieves higher compression ratios than existing algorithms in an off-line version, as well as a somewhat lower quality compression approach which is suitable for on-line use in dynamic circuit generation and other mapping-time critical situations. Target Architecture
Persistent, Tolerant or Subacute Infection in Borna Disease Virus-infected Rats (1983)

The rabbit-adapted Borna disease (BD) virus strain V was passaged by intracerebral infection of 1-day-old Wistar rats. Infectivity titres reached 10(8) infectious units per gram of brain 4 weeks after infection. No clinical signs were evident. The persistent infection could be induced with adapted or field strains of BD virus. Strains were identified by neutralization tests. The virulence of the rabbit-adapted BD virus for the rat increased with rat passages. The 5th passage induced clinical symptoms in animals infected at 1 week of age or older. Between 20% and 50% of diseased rats died. Virus-specific antigen was detectable immunohistologically in neurons of rats infected at all ages. Animals inoculated at 1 or 2 months of age, but not the neonatal rats, showed signs of inflammation in the brain. Infected rats produced specific antibodies. In the older groups (infected at ages of 1 or 2 months), and especially in surviving animals, occasionally, neutralizing antibodies with high titres were found. Transfer of primed spleen cells resulted in subacute disease. These findings demonstrate that neonatal rats can acquire a persistent, tolerant infection and that expression of disease is mediated by immunological factors.
Principles of gene manipulation : an introduction to genetic engineering (1981)

The basic philosophy governing the first edition of this text was to present the principles of gene manipulation, and their associated techniques, in sufficient detail to enable the non-specialist reader to understand them. It was also intended that the scope of this technology, and its potential impact on virtually all areas of biology, would be evident. The second and third editions were enlarged to cope with advances in the field as it had become apparent that, around a core of fundamental techniques concerning the manipulation of DNA in vitro, there was developing an ever-expanding repertoire of transformation techniques, library construction and screening methods, expression systems and host-vector systems. In this, the fourth edition, the authors keep to their basic philosophy in providing an introduction to the subject, identifying and explaining basic principles. Completely updated this edition provides an overview for researchers and students who already have some knowledge of recombinant DNA work.
Validation of a new dielectric device to assess changes of tissue water in skin and subcutaneous fat (2004)

Easily applicable and inexpensive water-specific techniques to evaluate local oedema, swollen tissue problems and fluid retention in humans are not available. In the present investigation a recently constructed non-invasive device for a local measurement of changes in tissue water in human skin and subcutaneous fat (SSF) was validated. The instrument transmits an ultra high-frequency electromagnetic (EM) wave of 300 MHz into a coaxial line and further into an open-ended coaxial probe which is in contact with the skin. Due to the dimensions of the applied probe the penetration of the EM field extends to subcutaneous fat. A major part of the EM energy is absorbed by tissue water while the rest is reflected back into a coaxial line. From the information of the reflected wave an electrical parameter, directly proportional to tissue water content, called a dielectric constant of SSF, was calculated. For system validation, the decrease of water content in SSF measured with the dielectric technique in the volar forearm of seven patients during haemodialysis treatment was compared with the decrease of the circumference of the forearm and the amount of fluid removed. Statistically highly significant correlations were obtained between the decreasing dielectric constant (i.e. water content) of the SSF and the fluid removed during haemodialysis treatment (r = -0.99, p < 0.01) and between the decreasing dielectric constant and the circumference of the arm (r = 0.97, p < 0.05). The sensitivity of the dielectric method was four-fold compared with the circumferential measurement. The repeatability 3.0% was not dependent on the phase of haemodialysis. The new device allows an easy and non-invasive measurement technique to assess changes of tissue water in SSF.
Synthesis of Potential Anticancer Agents. I. 5-Substituted 7-Methyl-s-triazolo [4, 3-α]-and-tetrazolo [1, 5-α]-pyrimidines. (1958)

A number of 5-substituted 7-methyl-s-triazolo [4, 3-α]-and-tetrazolo [1, 5-α] pyrimidines were prepared by nucleophilic displacement of the corresponding chloro compounds (VII and VIII). These compounds are being screened for antimetabolite and anticancer activity.