gebhart/patrepeval huggingface dataset:
Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies PotentPlasmodium falciparumDihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential (2011)

Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmacokinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.
Quantitative Trait Locus Mapping and Candidate Gene Analysis for Plant Architecture Traits Using Whole Genome Re-Sequencing in Rice (2014)

Plant breeders have focused on improving plant architecture as an effective means to increase crop yield. Here, we identify the main-effect quantitative trait loci (QTLs) for plant shape-related traits in rice (Oryza sativa) and find candidate genes by applying whole genome re-sequencing of two parental cultivars using next-generation sequencing. To identify QTLs influencing plant shape, we analyzed six traits: plant height, tiller number, panicle diameter, panicle length, flag leaf length, and flag leaf width. We performed QTL analysis with 178 F7 recombinant in-bred lines (RILs) from a cross of japonica rice line 'SNUSG1' and indica rice line 'Milyang23'. Using 131 molecular markers, including 28 insertion/deletion markers, we identified 11 main- and 16 minor-effect QTLs for the six traits with a threshold LOD value > 2.8. Our sequence analysis identified fifty-four candidate genes for the main-effect QTLs. By further comparison of coding sequences and meta-expression profiles between japonica and indica rice varieties, we finally chose 15 strong candidate genes for the 11 main-effect QTLs. Our study shows that the whole-genome sequence data substantially enhanced the efficiency of polymorphic marker development for QTL fine-mapping and the identification of possible candidate genes. This yields useful genetic resources for breeding high-yielding rice cultivars with improved plant architecture.
Metal hydride reductions of unsymmetrical cyclic anhydrides. The importance of the antiperiplanar effect on the regioselectivity of these reactions (1982)

A quantum mechanical study by the SCF abinitio method of the interaction of H − with methylsuccinic and 2,2-dimethylsuccinic anhydrides (naked and in the presence of a cation) suggests that nonperpendicular rearside attack cannot be the factor responsible for the regioselectivity of hydride transfer to the more sterically hindered carbonyl group. In this model, the nucleophilic attack at the less hindered carbonyl group is calculated to be of lower energy (with or without cation). Deformation of the planar succinic anhydride ring to the quasi-chair conformation is energetically favoured as it allows the nucleophile to attack both carbonyl functions antiperiplanar to a quasi axial C—H or C—C bond. The attack antiperiplanar to the C—CH 3 bond is lower in energy than the attack antiperiplanar to the C—H bond suggesting that the reduction will occur at the sterically more hindered carbonyl group which is in agreement with the experimental findings.
Controlling cell interactions by micropatterning in co-cultures: Hepatocytes and 3T3 fibroblasts (1997)

The repair or replacement of damaged tissues using in vitro strategies has focused on manipulation of the cell environment by modulation of cell-extracellular matrix interactions, cell-cell interactions, or soluble stimuli. Many of these environmental influences are easily controlled using macroscopic techniques; however, in co-culture systems with two or more cell types, cell-cell interactions have been difficult to manipulate precisely using similar methods. Although microfabrication has been widely utilized for the spatial control of cells in culture, these methods have never been adapted to the simultaneous co-cultivation of more than one cell type. We have developed a versatile technique for micropatterning of two different cell types based on existing strategies for surface modification with aminosilanes linked to biomolecules and the manipulation of serum content of cell culture media. This co-culture technique allowed manipulation of the initial cellular microenvironment without variation of cell number. Specifically, we were able to control the level of homotypic interaction in cultures of a single cell type and the degree of heterotypic contact in co-cultures over a wide range. This methodology has potential applications in tissue engineering, implant biology, and developmental biology, both in the arena of basic science and optimization of function for technological applications.
The effect of transforming growth factor-β2-specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma (1993)

This in vitro study was aimed at restitution of transforming growth factor (TGF)-beta 2-mediated suppression of T-lymphocyte activation within malignant gliomas. In early-passage tumor cell cultures of two glioblastomas (HTZ-153 and HTZ-209) and one malignant astrocytoma classified as World Health Organization Grade III (HTZ-243), autologous peripheral blood mononuclear cells were activated by interleukin-1 alpha and interleukin-2 in vitro (lymphokine-activated killer cells) and tested for cytotoxic and proliferative activity. In expression studies (Western blot and Northern hybridization) of all three tumors, TGF-beta could be detected at the protein and messenger ribonucleic acid (mRNA) levels. A polyclonal anti-TGF-beta neutralizing antibody did not enhance lymphocyte proliferation upon stimulation with tumor targets (3H-thymidine incorporation) and slightly stimulated lymphocyte cytotoxicity against autologous target cells. Preincubation of target cells for 12 hours with TGF-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides (S-ODN's) did, however, enhance lymphocyte proliferation up to 2.5-fold and autologous tumor cytotoxicity up to 60%, compared to controls not treated with S-ODN's. Incubation of tumor cells with TGF-beta 2-specific S-ODN's resulted in decreased TGF-beta-specific immunoreactivity in cultured glioma cells, in reduced TGF-beta 2 protein concentration (Western blot), and in a change in the expression pattern of TGF-beta 2 mRNA's. These observations may have implications for in vivo and in vitro activation of a cellular immune response against autologous malignant glioma cells.
Immunization Strategies To Block the Herpes Simplex Virus Type 1 Immunoglobulin G Fc Receptor (2004)

Herpes simplex virus type 1 (HSV-1) glycoprotein gE functions as an immunoglobulin G (IgG) Fc receptor (FcgammaR) that promotes immune evasion. When an IgG antibody binds by the F(ab')(2) domain to an HSV antigen, the Fc domain of some of the same antibody molecules binds to the FcgammaR, which blocks Fc-mediated functions. gE is a type 1 membrane glycoprotein with a large ectodomain that is expressed on the virion envelope and infected-cell surface. Our goal was to determine if immunizing with gE protein fragments could produce antibodies that bind by the F(ab')(2) domain to gE and block the FcgammaR, as measured by competitively inhibiting nonimmune human IgG binding to the FcgammaR. Three gE peptides were constructed in baculovirus spanning almost the entire ectodomain and used to immunize mice and rabbits. Two fragments were highly effective at producing antibodies that bind by the F(ab')(2) domain and block the FcgammaR. The most potent of these two antibodies was far more effective at blocking the FcgammaR than antibodies that are only capable of binding by the Fc domains to the FcgammaR, including anti-gC, anti-gD, and nonimmune IgG. These results suggest that immunizing with gE fragments has potential for preventing immune evasion by blocking activities mediated by the HSV-1 FcgammaR.
Other Kinases Can Substitute for Jak2 in Signal Transduction by Interferon-γ (1996)

Each cytokine which utilizes the Jak-Stat signal transduction pathway activates a distinct combination of members of the Jak and Stat families. Thus, either the Jaks, the Stats, or both could contribute to the specificity of ligand action. With the use of chimeric receptors involving the interferon gamma receptor (IFN-gammaR) complex as a model system, we demonstrate that Jak2 activation is not an absolute requirement for IFN-gamma signaling. Other members of the Jak family can functionally substitute for Jak2. IFN-gamma can signal through the activation of Jak family members other than Jak2 as measured by Statlalpha homodimerization and major histocompatibility complex class I antigen expression. This indicates that Jaks are interchangeable and indiscriminative in the Jak-Stat signal transduction pathway. The necessity for the activation of one particular kinase during signaling can be overcome by recruiting another kinase to the receptor complex. The results may suggest that the Jaks do not contribute to the specificity of signal transduction in the Jak-Stat pathway to the same degree as Stats.
A new vector quantization clustering algorithm (1989)

The pairwise nearest neighbor (PNN) algorithm is presented as an alternative to the Linde-Buzo-Gray (1980, LBG) (generalized Lloyd, 1982) algorithm for vector quantization clustering. The PNN algorithm derives a vector quantization codebook in a diminishingly small fraction of the time previously required, without sacrificing performance. In addition, the time needed to generate a codebook grows only O(N log N) in training set size and is independent of the number of code words desired. Using this method, one can either minimize the number of code words needed subject to a maximum rate. The PNN algorithm can be used with squared error and weighted squared error distortion measure. Simulations on a variety of images encoded at 1/2 b/pixel indicate that PNN codebooks can be developed in roughly 5% of the time required by the LBG algorithm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Different Intravitreal Properties of Three Triamcinolone Formulations and Their Possible Impact on Retina Practice (2013)

Triesence demonstrated a significantly slower dissolution profile and lower free drug level in the vitreous than the other preserved triamcinolone, which may translate into a longer therapeutic duration and lower rate of drug-associated complications.
Experimental Repetitive Quantum Error Correction (2011)

The computational potential of a quantum processor can only be unleashed if errors during a quantum computation can be controlled and corrected for. Quantum error correction works if imperfections of quantum gate operations and measurements are below a certain threshold and corrections can be applied repeatedly. We implement multiple quantum error correction cycles for phase-flip errors on qubits encoded with trapped ions. Errors are corrected by a quantum-feedback algorithm using high-fidelity gate operations and a reset technique for the auxiliary qubits. Up to three consecutive correction cycles are realized, and the behavior of the algorithm for different noise environments is analyzed.
Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method (2010)

This brief perspective article focuses on the most common errors and pitfalls, as well as the do's and don'ts in drug combination studies, in terms of experimental design, data acquisition, data interpretation, and computerized simulation. The Chou-Talalay method for drug combination is based on the median-effect equation, derived from the mass-action law principle, which is the unified theory that provides the common link between single entity and multiple entities, and first order and higher order dynamics. This general equation encompasses the Michaelis-Menten, Hill, Henderson-Hasselbalch, and Scatchard equations in biochemistry and biophysics. The resulting combination index (CI) theorem of Chou-Talalay offers quantitative definition for additive effect (CI = 1), synergism (CI < 1), and antagonism (CI > 1) in drug combinations. This theory also provides algorithms for automated computer simulation for synergism and/or antagonism at any effect and dose level, as shown in the CI plot and isobologram, respectively.
Click and Pick: Identification of Sialoside Analogues for Siglec‐Based Cell Targeting (2012)

Click 'n' chips: Azide and alkyne-bearing sialic acids (purple diamond; see picture) were subjected to high-throughput click chemistry to generate a library of sialic acid analogues. Microarray printing of the library and screening with the siglec family of sialic-acid-binding proteins, led to the identification of high-affinity ligands for siglec-9 and siglec-10.
Expression of the coat protein of potato virus X from a dicistronic mRNA in transgenic potato plants. (1997)

Transgenic potato plants were generated which express a dicistronic mRNA corresponding to the 8 kDa protein and coat protein (CP) genes of potato virus X (PVX). Northern blot analysis of RNA isolated from these plants indicated that both the 8 kDa protein and the CP are translated from this dicistronic mRNA. Expression of both of these proteins in transgenic plants was demonstrated by Western blot analysis, and suggests that translation of CP takes place either by initiation by internal entry of ribosomes or by a termination/reinitiation mechanism. CP was detected in protoplasts electroporated with RNA transcripts of the dicistronic construct in the presence or absence of a stable hairpin structure at the 5' terminus, suggesting that the former model is more likely. Similar results were obtained when a DNA fragment containing the PVX CP leader sequence was placed between two reporter genes in the transient assay system. These results suggest that potexvirus CP expression may take place from the genomic RNA as well as from the subgenomic RNA.
Respiratory Syncytial Viral Infection in Infants with Congenital Heart Disease (1982)

Occasional reports have suggested that infants with congenital heart disease may have an increased risk of severe illness from respiratory syncytial virus (RSV) infection. We prospectively studied 699 infants hospitalized during the winters of 1976 through 1980, when RSV was prevalent in the community; 229 of these infants had proved RSV infections acquired either before admission or during hospitalization; 27 had both congenital heart disease and RSV infection, and 46 had congenital heart disease without RSV infection. Infected infants with congenital heart disease had significantly more severe illness than those without congenital heart disease, as judged by the requirement for intensive care and assisted ventilation and by the mortality rate (37 per cent vs. 1.5 per cent, P less than 0.01). The infection was acquired nosocomially by 21 per cent of infected infants; the mortality rate from nosocomial infection was also higher in infants with congenital heart disease (44 per cent vs. 5 per cent, P less than 0.01). Pulmonary hypertension was the one condition particularly associated with severe RSV illness. Eight of the 11 infants (73 per cent) with congenital heart disease and pulmonary hypertension died during their RSV illness. The courses in infants with congenital heart disease with and without RSV infection were also compared. Their ages, types of cardiac lesions, and incidence of pulmonary hypertension were similar, but the infants with RSV infection had a higher mortality rate (37 per cent vs. 6.5 per cent, P less than 0.1).
A Collection of mRNA Species That Are Inducible in the RAW 264.7 Mouse Macrophage Cell Line by Gamma Interferon and Other Agents (1992)

To identify genes induced during macrophage activation, a cDNA library was prepared from cultures of the RAW 264.7 mouse macrophage cell line that had been treated with conditioned medium from mitogen-stimulated spleen cells, and the cDNA library was screened by differential plaque hybridization. Eleven cDNA clones, designated CRG-1 through CRG-11, corresponding to mRNA species inducible in RAW 264.7 cells by the spleen cell conditioned medium, were isolated. Inductions were not blocked by cycloheximide. All of the mRNAs were inducible by gamma interferon, and some were also inducible by alpha and beta interferons, by lipopolysaccharide, by phorbol 12-myristate 13-acetate, and by the calcium ionophore A23187. Sequencing of the cDNAs revealed that CRG-1, CRG-3, and CRG-5 are cDNAs of recently identified transcription factors IRF-1, zif/268, and LRF-1 respectively. As previously reported, CRG-2 and CRG-10 (MIG) encode new members of the platelet factor 4 family of cytokines. CRG-6 corresponds to a new member of a family of interferon-inducible genes clustered on mouse chromosome 1, CRG-9 corresponds to a prostaglandin synthase homolog, CRG-8 corresponds to beta 2-microglobulin, and CRG-4 corresponds to metallothionein II. CRG-11 contains sequences of a truncated L1Md repetitive element as well as nonrepetitive sequences. The nonrepetitive sequence of CRG-11 as well as the sequences of CRG-7 are not closely related to published sequences. The CRG genes and proteins are of interest because of their involvement in macrophage activation, because of their roles as mediators of the effects of gamma interferon and other pleiotropic agents, and because of their usefulness as tools for studying the signal pathways through which gamma interferon and other inducers exert their effects on gene and protein expression.
<title>The Light Beam Profiler--Past, Present, And Future</title> (1981)

Some of you attended the workshop on &quot;Replication Technology&quot; which was sponsored by M.I.T. in January, 1979. On that occasion, I reviewed the early work which led up to the recent, renewed interest in photo-sculpture. I was pleasantly surprised at the favorable response to that presentation and for today&apos;s seminar I thought I would take a similar approach to a closely related subject. My topic is somewhat narrower, but I hope it will be interesting and instructive to trace the origins of a simple but rather elegant technique for 3-D sensing--light beam profiling--and examine the current status and future pros-pects for this relatively inexpensive, but quite versatile technology.
Protecting sensitive web content from client-side vulnerabilities with CRYPTONS (2013)

Web browsers isolate web origins, but do not provide direct abstractions to isolate sensitive data and control computation over it within the same origin. As a result, guaranteeing security of sensitive web content requires trusting all code in the browser and client-side applications to be vulnerability-free. In this paper, we propose a new abstraction, called Crypton, which supports intra-origin control over sensitive data throughout its life cycle. To securely enforce the semantics of Cryptons, we develop a standalone component called Crypton-Kernel, which extensively leverages the functionality of existing web browsers without relying on their large TCB. Our evaluation demonstrates that the Crypton abstraction supported by the Crypton-Kernel is widely applicable to popular real-world applications with millions of users, including webmail, chat, blog applications, and Alexa Top 50 websites, with low performance overhead.
STEREOSELECTIVE INHIBITION OF CHOLESTEROL ESTERASE BY ENANTIOMERIC PHOSPHONATES (1997)

Abstract Enantiomers of methyl 2-naphthyl hexylphosphonate (MNHP) were prepared via diastereomeric phosphonamidate intermediates. The enantiomers exhibit stereoselective inhibition of purified porcine pancreatic cholesterol esterase; the first-order inhibition rate constant of the (-)-isomer is approximately fourfold higher than the rate constant of the (+)-isomer.
Design and Implementation of Wireless Data Transceiver Terminal Based on GPRS (2012)

Aim to the problem of environmental monitoring in real-time remote data collection, transmission, remote control and analysis, the ZigBee protocol and communication principle is discussed, Through GPRS technology to achieve the remote monitor and information transmit. Based on the Core board S3C2440 to design the circuits; design and complete embedded software WSNIPS and the server software in the VS2005 development. Achieved through MC35i module connection GPRS network and Internet monitoring center for the overall monitoring of the urban environment provides a good platform.
Plant Regeneration from Tissue Cultures of Maize1 (1975)

Abstract Effective utilization of cell and tissue culture methods in Zea mays research requires cultures capable of plant regeneration. These differentiated plants would provide a direct link with conventional genetic and breeding procedures. Maize callus from embryo scutellar tissues was initiated and maintained on MS medium inorganic components, Straus medium vitamins and amino acids, 20 g sucrose and 8 g agar per liter, and 2 mg 2,4‐dichlorophenoxyacetic acid (2,4‐D)/liter. Callus has been maintained subculture every 21 to 28 days and has remained capable of differentiation for 9 months. Regeneration of complete plants was accomplished by subculture of callus to 0.25 mg 2,4‐D/liter for 30 days followed by transfer to 2,4‐D‐free culture medium. At 0.25 mg 2,4‐D/liter numerous curled and wrinkled leaves developed. Approximately 200 complete plants have been differentiated. after transfer to the 2,4‐D‐free medium. Root tip cells from five plants indicated that each had 20 chromosomes. After transplantation to soil, 10 to 15% of the plants survived and grew normally. The optimum embryo age for scutellar callus initiation was 18 days post‐pollination. Hormone combinations such as 1 mg 2,4‐D, 4 mg a‐naphthaleneacetic acid (NAA), and 0.05 mg 6‐(γ,γ‐dimethyl allylamino)‐purine (2iP)/liter may increase the efficiency of scutellar callus initiation.
The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor. (1993)

The human coagulation system continuously generates very small quantities of Factor Xa and thrombin. Current evidence suggests that basal level activation of the hemostatic mechanism occurs via Factor VIIa-dependent activation of Factor X, but direct proof has not been available for the participation of tissue factor in this pathway. To examine this issue, we infused relatively high concentrations of recombinant Factor VIIa (approximately 50 micrograms/kg body wt) into normal chimpanzees and observed significant increases in the plasma levels of Factor IX activation peptide, Factor X activation peptide, and prothrombin activation fragment F1+2. Metabolic turnover studies with radiolabeled Factor IX activation peptide, Factor X activation peptide, and F1+2 indicate that elevated levels of the activation peptides are due to accelerated conversion of the three coagulation system zymogens into serine proteases. The administration of a potent monoclonal antibody to tissue factor, which immediately neutralizes function of the Factor VIIa-tissue factor complex in vitro, abolishes the activation of Factor X and prothrombin mediated by the infused recombinant protein, and also suppresses basal level activation of Factor IX and Factor X. The above results suggest that recombinant Factor VIIa functions as a prohemostatic agent by interacting with endogenous tissue factor sites, but definitive proof will require studies in hemophilic animals using relevant hemostatic endpoints.