gebhart/patrepeval huggingface dataset:
Expression of functional Raphanus sativus antifungal protein in yeast (1994)

Rs-AFP2 is a 51 amino acid cysteine-rich peptide isolated from radish (Raphanus sativus) seeds that exhibits potent inhibitory activity against filamentous fungi. A cDNA clone encoding the Rs-AFP2 preprotein was modified by recombinant DNA methods to allow expression in the yeast Saccharomyces cerevisiae. This peptide was expressed in yeast as a fusion protein carrying at its N-terminus the prepro-sequences derived from the precursor of the yeast pheromone mating factor alpha 1. These sequences allow secretion of the biologically active peptide in a correctly processed form. Deletion of the mating factor alpha 1 pro-peptide drastically reduced the expression level of the peptide.
Contributions of glutenin and puroindoline genes to grain quality traits in southern Australian wheat breeding programs (2006)

Glutenin genes were known to influence maximum dough resistance (Rmax), dough extensibility (extensibility), and dough development time, whereas puroindoline genes were known to influence grain hardness, flour water absorption (water absorption), and milling yield. These are important determinants of grain quality of wheat in Australia. This study was conducted to investigate the combined effect of these genes on Rmax, extensibility, dough development time, water absorption, and milling yield in a large dataset assembled from the breeding programs based at Horsham, Victoria; Roseworthy, South Australia; and Wagga Wagga, New South Wales; for at least 10 seasons. The effect of the glutenin genes on Rmax, extensibility, and dough development time was confirmed, as was the effect of the puroindoline genes on water absorption and milling yield. In addition, puroindoline genes were shown to significantly affect extensibility and dough development time. The Pina-D1a/Pinb-D1b genotype increased extensibility, dough development time, and milling yield relative to the Pina-D1b/Pinb-D1a genotype. Both of these genotypes are present in cultivars classified as hard-grained in southern Australia. Therefore, the allelic composition of both glutenin and puroindoline genes is required to predict the grain quality of hard wheat in southern Australian breeding programs. The glutenin and puroindoline genes in combination accounted for more than 50% of the genotypic variance for these traits, except for milling yield, but a substantial proportion of the genotypic variation could not be attributed to these genes, indicating that other genes affecting the traits were present in the populations of these wheat-breeding programs.
ChemInform Abstract: Synthesis, Structure—Activity Relationships, and Pharmacological Profile of 9‐Amino‐4‐oxo‐1‐phenyl‐3,4,6,7‐tetrahydro[1,4]diazepino [6,7,1‐hi]indoles: Discovery of Potent, Selective Phosphodiesterase Type 4 Inhibitors. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Acyclic and Cyclic Ureas (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Calreticulin modulates cell adhesiveness via regulation of vinculin expression. (1996)

Calreticulin is an ubiquitous and highly conserved high capacity Ca(2+)-binding protein that plays a major role in Ca2+ storage within the lumen of the ER. Here, using L fibroblast cell lines expressing different levels of calreticulin, we show that calreticulin plays a role in the control of cell adhesiveness via regulation of expression of vinculin, a cytoskeletal protein essential for cell-substratum and cell-cell attachments. Both vinculin protein and mRNA levels are increased in cells overexpressing calreticulin and are downregulated in cells expressing reduced level of calreticulin. Abundance of actin, talin, alpha 5 and beta 1 integrins, pp125 focal adhesion kinase, and alpha-catenin is not affected by the differential calreticulin expression. Overexpression of calreticulin increases both cell-substratum and cell-cell adhesiveness of L fibroblasts that, most surprisingly, establish vinculin-rich cell-cell junctions. Upregulation of calreticulin also affects adhesion-dependent phenomena such as cell motility (which decreases) and cell spreading (which increases). Downregulation of calreticulin brings about inverse effects. Cell adhesiveness is Ca2+ regulated. The level of calreticulin expression, however, has no effect on either the resting cytoplasmic Ca2+ concentration or the magnitude of FGF-induced Ca2+ transients. Calreticulin, however, participates in Ca2+ homeostasis as its level of expression affects cell viability at low concentrations of extracellular Ca2+. Consequently, we infer that it is not the Ca2+ storage function of calreticulin that affects cell adhesiveness. Neither endogenous calreticulin nor overexpressed green fluorescent protein-calreticulin construct can be detected outside of the ER. Since all of the adhesion-related effects of differential calreticulin expression can be explained by its regulation of vinculin expression, we conclude that it is the ER-resident calreticulin that affects cellular adhesiveness.
Motoneuronal output and gradation of effort in attempts to contract acutely paralysed leg muscles in man. (1993)

1. The study was designed to determine the degree to which normal subjects can control motoneurones innervating a leg muscle when acutely deprived of muscle afferent feedback. Microneurographic recordings were made from eighteen motor fascicles in the common peroneal nerve, of which thirteen innervated tibialis anterior and five toe dorsiflexor muscles. The nerve was then blocked completely at a distal site near the fibular head with local anaesthetic. A sequence of tests was performed with each fascicle to determine the degree to which the subject could control the motoneuronal drive to the paralysed muscle. 2. During a complete distal block of the common peroneal nerve, motoneurones innervating tibialis anterior were frequently activated during weak attempted contraction of the synergist toe extensors and vice versa. 3. When subjects attempted contractions of the paralysed muscles at a constant effort, pressure applied to the dorsum of the foot caused relatively small changes in the level of neural output, producing a small increase in motoneuronal drive to tibialis anterior, but no consistent change in the drive to toe extensor fascicles. 4. Subjects were able to increase the motoneuronal drive to the paralysed tibialis anterior in five steps of effort each lasting 10 s. The level of motor output increased linearly with step number, but declined as the step was maintained, more so when auditory feedback was withdrawn. 5. There was hysteresis in the relationship between motoneuronal output and force (measured on the contralateral side) during attempts to make slowly increasing then decreasing ramps of effort on both sides over 20-120 s. Motor drive to the paralysed muscle increased disproportionately rapidly compared with contralateral force when subjects attempted bilaterally symmetrical increasing efforts. 6. Subjects attempted to activate the paralysed muscle group maximally for 20-30 s with auditory feedback of the neurogram and verbal encouragement. There was a small statistically significant reduction in the motoneuronal output 5-10 s into the 30 s effort but, with further encouragement, it recovered towards the end of the effort. 7. When compared directly in the same recording sequences, attempts to make rapid brief maximal efforts (2-3 s duration) produced the same motoneuronal output as attempts to make sustained efforts. 8. Similar results occurred when the motoneuronal output to tibialis anterior was recorded during a selective distal block of tibialis anterior sparing toe dorsiflexors.(ABSTRACT TRUNCATED AT 400 WORDS)
Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer (2012)

Endometrial cancer is the most common gynecological malignancy, with more than 280,000 cases occurring annually worldwide. Although previous studies have identified important common somatic mutations in endometrial cancer, they have primarily focused on a small set of known cancer genes and have thus provided a limited view of the molecular basis underlying this disease. Here we have developed an integrated systems-biology approach to identifying novel cancer genes contributing to endometrial tumorigenesis. We first performed whole-exome sequencing on 13 endometrial cancers and matched normal samples, systematically identifying somatic alterations with high precision and sensitivity. We then combined bioinformatics prioritization with high-throughput screening (including both shRNA-mediated knockdown and expression of wild-type and mutant constructs) in a highly sensitive cell viability assay. Our results revealed 12 potential driver cancer genes including 10 tumor-suppressor candidates (ARID1A, INHBA, KMO, TTLL5, GRM8, IGFBP3, AKTIP, PHKA2, TRPS1, and WNT11) and two oncogene candidates (ERBB3 and RPS6KC1). The results in the "sensor" cell line were recapitulated by siRNA-mediated knockdown in endometrial cancer cell lines. Focusing on ARID1A, we integrated mutation profiles with functional proteomics in 222 endometrial cancer samples, demonstrating that ARID1A mutations frequently co-occur with mutations in the phosphatidylinositol 3-kinase (PI3K) pathway and are associated with PI3K pathway activation. siRNA knockdown in endometrial cancer cell lines increased AKT phosphorylation supporting ARID1A as a novel regulator of PI3K pathway activity. Our study presents the first unbiased view of somatic coding mutations in endometrial cancer and provides functional evidence for diverse driver genes and mutations in this disease.
Chemistry and Chemical Reactivity (1987)

Quality writing, seamless technology integration, and a rich ancillary package are hallmarks of John C. Kotz and Paul M. Treichel, Jr.'s CHEMISTRY AND CHEMICAL REACTIVITY. Now thoroughly revised and enhanced, the fifth edition of this best-selling text will bring students to a new level of understanding and appreciation for chemistry's vital role in their lives. By emphasizing the close interrelationship of the macroscopic, symbolic, and particulate levels of chemistry, Kotz and Treichel provide an important organizing principle that carries throughout the book. The text's significantly revised art program reveals these three levels in engaging detail. This new art program is fully integrated with CHEMISTRY AND CHEMICAL REACTIVITY'S unparalleled CD-ROM, GENERAL CHEMISTRY INTERACTIVE, VERSION 3.0. With hundreds of guided simulations, animations, and video clips, as well as new Intelligent Tutors that guide students step-by-step through problems, GENERAL CHEMISTRY INTERACTIVE is the benchmark learning tool by which all others are measured-and it is included with every new copy of the text.
Early Outpatient Treatment With Remdesivir in Patients at High Risk for Severe COVID-19: A Prospective Cohort Study (2022)

Early outpatient treatment with remdesivir significantly reduces hospitalization or death by 84% in high-risk, majority immunosuppressed patients with Omicron variant COVID-19.
Size of the Streptococcus mutans GS-5 chromosome as determined by pulsed-field gel electrophoresis (1990)

Rare cutting restriction endonucleases were used to cut the Streptococcus mutans chromosome into large fragments. Restriction enzymes utilizing recognition sites containing 6-, 7-, or 8-base-pair sequences with only G and C nucleotides produced few fragments, most of which were greater than 100 kilobase pairs in size. Addition of the fragments from digests of SmaI, NotI, ApaI, RsrII, and EagI yielded a molecular size for the S. mutans GS-5 genome of 2,819 +/- 60 kilobase pairs.
A bispecific antibody agonist of the IL-2 heterodimeric receptor preferentially promotes in vivo expansion of CD8 and NK cells (2021)

The use of recombinant interleukin-2 (IL-2) as a therapeutic protein has been limited by significant toxicities despite its demonstrated ability to induce durable tumor-regression in cancer patients. The adverse events and limited efficacy of IL-2 treatment are due to the preferential binding of IL-2 to cells that express the high-affinity, trimeric receptor, IL-2Rαβγ such as endothelial cells and T-regulatory cells, respectively. Here, we describe a novel bispecific heavy-chain only antibody which binds to and activates signaling through the heterodimeric IL-2Rβγ receptor complex that is expressed on resting T-cells and NK cells. By avoiding binding to IL-2Rα, this molecule circumvents the preferential T-reg activation of native IL-2, while maintaining the robust stimulatory effects on T-cells and NK-cells in vitro. In vivo studies in both mice and cynomolgus monkeys confirm the molecule's in vivo biological activity, extended pharmacodynamics due to the Fc portion of the molecule, and enhanced safety profile. Together, these results demonstrate that the bispecific antibody is a safe and effective IL-2R agonist that harnesses the benefits of the IL-2 signaling pathway as a potential anti-cancer therapy.
Protein-protein Interaction: Network Alignment (2006)

In the last few years the amount of available data on protein-protein interaction (PPI) networks have increased rapidly, spanning different species such as yeast, bacteria, fly, worm and Human. The rapid growth is shown in Figure 1. Besides the availability of the data, other incentives to analyze several PPI networks at once are validation of our conclusions over several networks and prediction of unknown protein function and interactions. The scribe is organized as follows: In section 2 we describe the network alignment and network querying problems. In section 3 we describe network pairwise alignment, and its usage in finding conserved protein paths and complexes in PPI networks. The comparative analysis approach, which allows us for detecting similar functionality by looking at multiple highly conserved interactions between similar proteins from different species, is presented in section 4 using QPath, an efficient algorithm for path queries, based on dynamic programming. In section 5 we show PPI networks can be used to predict functional orthologous genes. In section 6 we describe a model that extends the pairwise alignment model to a multiple alignments. Finally, section 7 contains a brief summary.
In Vivo Selection of Respiratory Syncytial Viruses Resistant to Palivizumab (2005)

Palivizumab (PZ) is the only monoclonal antibody currently available for use in humans against an infectious disease. PZ is administered prophylactically for respiratory syncytial virus (RSV) infections. RSV selected in cell culture for growth in the presence of PZ develops F gene mutations and can be resistant to PZ prophylaxis in cotton rats. Here, we evaluated the potential for PZ-resistant RSV mutants to arise in vivo. Cotton rats were immunosuppressed with cyclophosphamide, administered PZ, and inoculated intranasally with RSV. Lungs were harvested 12 weeks after RSV infection, reverse transcription-PCR-amplified F gene fragments were cloned into plasmids, and the nucleotide sequences of the cloned cDNAs were determined. Three of the five animals had mixed populations of lung virus, and over 50% of the clones from the three animals revealed F gene mutations associated with resistance to PZ. A virus completely resistant to PZ neutralization was recovered from the lung homogenate of a rat that had received PZ. Thus, prolonged pulmonary replication of RSV in the presence of PZ was followed by the appearance of viruses resistant to PZ. The potential for the development of resistance is a consideration as the antibody is used prophylactically against RSV and as passively administered antibodies are under development for other infections, including emerging viruses and agents of biodefense.
DNA as therapeutics; an update (2009)

Human gene therapy is the introduction of new genetic material into the cells of an individual with the intention of producing a therapeutic benefit for the patient. Deoxyribonucleic acid and ribonucleic acid are used in gene therapy. Over time and with proper oversight, human gene therapy might become an effective weapon in modern medicine's arsenal to help fight diseases such as cancer, acquired immunodeficiency syndrome, diabetes, high blood pressure, coronary heart disease, peripheral vascular disease, neurodegenerative diseases, cystic fibrosis, hemophilia and other genetic disorders. Gene therapy trials in humans are of two types, somatic and germ line gene therapy. There are many ethical, social, and commercial issues raised by the prospects of treating patients whose consent is impossible to obtain. This review summarizes deoxyribonucleic acid-based therapeutics and gene transfer technologies for the diseases that are known to be genetic in origin. Deoxyribonucleic acid-based therapeutics includes plasmids, oligonucleotides for antisense and antigene applications, deoxyribonucleic acid aptamers and deoxyribonucleic acidzymes. This review also includes current status of gene therapy and recent developments in gene therapy research.
P3‐275: Abeta‐oligomer selective antibody A‐887755 exhibits a favorable profile for Alzheimer's disease immunotherapy compared to Abeta‐peptide unselective antibodies (2009)

Although Amyloid-beta (Abeta) fibrils within Abeta plaques are a hallmark of Alzheimer's disease (AD) during the past decade a paradigm shift occurred accounting Abeta-oligomers as the crucial neuropathogenic culprit of AD. In addition, Abeta-monomer was shown to be produced and metabolized in high amounts and associated with physiological brain function (Bateman et al. 2006). Here, we show that a synthetic, homogenous Abeta20-42 oligomer preparation (named Abeta20-42 Globulomer, Barghorn et al. 2005) is useful to generate monoclonal antibodies that selectively detect Abeta-oligomers in various synthetic and biological Abeta preparations while discriminating Abeta-monomer or Abeta-fibrils. We propose such Abeta-oligomer selective antibodies, like A-887755, as favorable for passive AD immunotherapy. We tested the capability of the Globulomer-specific antibody A-887755 to prevent Globulomer binding to primary hippocampal neurons in an excess of monomeric Abeta40/42 peptide thus trying to mimic the in vivo situation of passive AD immunotherapy. Under cell culture conditions Abeta20-42 Globulomers bind in a punctuated manner to dendritic processes of primary hippocampal neurons. Preincubation with Globulomer-specific antibody A-887755 at equimolar concentrations prevents Abeta20-42 Globulomer binding even in the presence of excess Abeta40/42 monomer. In contrast, 18-fold higher concentrations of Abeta-peptide unselective antibodies under otherwise identical conditions do not prevent Abeta20-42 Globulomer binding. Abeta-oligomers are regarded as the major neuropathogenic Abeta-species in AD. Passive immunotherapy with Abeta-peptide unselective antibodies can in principle neutralize Abeta-oligomer-mediated effects, although these antibodies also recognize Abeta-fibrils and Abeta-monomer. We propose that exclusively targeting Abeta-oligomers with Globulomer selective antibodies like A-887755 has major advantages. Firstly, targeting exclusively Abeta-oligomers as the neuropathogenic culprit of AD minimizes potential side effects by not binding to other Abeta-species such as Abeta-monomer, sAPPalpha, and Abeta-fibrils. Secondly, A-887755 is not consumed by binding to non disease related Abeta-peptide species, in particular Abeta-monomer. In summary these characteristics synergistically provide Globulomer specific antibody A-887755 with a highly favourable profile compared to Abeta-peptide unselective antibodies for AD immunotherapy.
Arabidopsis thaliana PAD4 encodes a lipase-like gene that is important for salicylic acid signaling (1999)

The Arabidopsis PAD4 gene previously was found to be required for expression of multiple defense responses including camalexin synthesis and PR-1 gene expression in response to infection by the bacterial pathogen Pseudomonas syringae pv. maculicola. This report describes the isolation of PAD4. The predicted PAD4 protein sequence displays similarity to triacyl glycerol lipases and other esterases. The PAD4 transcript was found to accumulate after P. syringae infection or treatment with salicylic acid (SA). PAD4 transcript levels were very low in infected pad4 mutants. Treatment with SA induced expression of PAD4 mRNA in pad4-1, pad4-3, and pad4-4 plants but not in pad4-2 plants. Induction of PAD4 expression by P. syringae was independent of the regulatory factor NPR1 but induction by SA was NPR1-dependent. Taken together with the previous observation that pad4 mutants have a defect in accumulation of SA upon pathogen infection, these results suggest that PAD4 participates in a positive regulatory loop that increases SA levels, thereby activating SA-dependent defense responses.
Heparin-Binding EGF-Like Growth Factor (HB-EGF) Decreases Oxygen Free Radical Production In Vitro and In Vivo (2002)

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to protect intestinal epithelial cells from anoxia/reoxygenation in vitro, and to protect the intestines from ischemia/reperfusion (I/R) injury in vivo. The goal of the present study was to determine whether the cytoprotective effects of HB-EGF were due, in part, to its ability to decrease reactive oxygen species (ROS) production. Human whole blood, polymorphonuclear leukocytes, and monocytes, as well as rat intestinal epithelial cells, were exposed to stimuli designed to produce an oxidative burst in these cells. Treatment of the cells with HB-EGF led to a significant decrease in oxidative burst production. In vivo, total midgut I/R injury in rats led to increased ROS production, which was markedly decreased by HB-EGF treatment. Histochemically, I/R injury led to increased ROS production, which was significantly decreased with HB-EGF treatment. HB-EGF cytoprotection is due, in part, to its ability to decrease ROS production. Future studies will determine the mechanisms by which HB-EGF exerts these effects.
A study of phase noise in CMOS oscillators (1996)

This paper presents a study of phase noise in two inductorless CMOS oscillators. First-order analysis of a linear oscillatory system leads to a noise shaping function and a new definition of Q. A linear model of CMOS ring oscillators is used to calculate their phase noise, and three phase noise phenomena, namely, additive noise, high-frequency multiplicative noise, and low-frequency multiplicative noise, are identified and formulated. Based on the same concepts, a CMOS relaxation oscillator is also analyzed. Issues and techniques related to simulation of noise in the time domain are described, and two prototypes fabricated in a 0.5-/spl mu/m CMOS technology are used to investigate the accuracy of the theoretical predictions. Compared with the measured results, the calculated phase noise values of a 2-GHz ring oscillator and a 900-MHz relaxation oscillator at 5 MHz offset have an error of approximately 4 dB.