gebhart/patrepeval huggingface dataset:
The synthesis of 2‐chloromethylpyridine from 2‐picoline‐<i>N</i>‐oxide (1981)

Abstract Phosphoryl chloride reacts with 2‐picoline‐ N ‐oxide in the presence of triethylamine to give 2‐chloromethylpyridine in 90% conversion with 98% selectivity. Diethylchlorophosphate, ethyl chloroformate, chloroacetyl chloride and phosgene also react with 2‐picoline‐ N ‐oxide to give 2‐chloromethylpyridine in moderate yields. Other potential chlorinating agents, titanium tetrachloride, zinc chloride, magnesium chloride and sulfuryl chloride, did not convert 2‐picoline N ‐oxide into 2‐chloromethylpyridine.
Abstract 3301: Guanidinium antisense oligonucleotides for cancer therapy. (2013)

Abstract Molecular targeted therapies are being tested in several clinical settings to target cancer. Most of the drugs being tested are small molecule inhibitors or antibodies that are specific to target proteins. Several of which have reduced target specificity or the tumor develops resistance to the drugs. This results in poor clinical outcomes. An approach that is highly specific and yet malleable enough to circumvent resistance mechanisms would be highly appealing. We have developed an antisense approach that can specifically bind to the mRNA of target proteins preventing translation and resulting in lower protein levels. In addition, unlike conventional antisense approaches, our antisense oligonucleotide carries a pseudo-peptide backbone with positively charged guanidinium residues rendering these resistant to nucleases and proteases. The oligomer binds nucleic acids with high sequence specificity and the hybridized complex is highly stable. As a proof of principle, we developed a 16 base antisense oligomer targeting the epidermal growth factor receptor (EGFR). EGFR is upregulated in several cancers and correlates with a poor prognosis. We tested the guanidinium-peptide nucleic acid (GPNA) EGFR antisense oligomer in tumors of the head and neck, lung and bladder. We carried out in vitro and in vivo studies including uptake and antitumor efficacy. Our data demonstrate that EGFR levels and cell survival are significantly reduced upon EGFRAS GPNA administration but not a scrambled control. Further, the EGFRAS GPNA effectively reduced levels of a constitutively active mutant EGFR (EGFRvIII). In vivo, EGFRAS GPNA had antitumor effects comparable to EGFR inhibitors that are under clinical testing namely erlotinib and cetuximab. Our data demonstrate that GPNA oligomers are an effective therapeutic approach against several tumor types. Citation Format: Sufi M. Thomas, Danith Ly. Guanidinium antisense oligonucleotides for cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3301. doi:10.1158/1538-7445.AM2013-3301
Discovery and Development of Hepatitis C Virus NS5A Replication Complex Inhibitors (2014)

Lead inhibitors that target the function of the hepatitis C virus (HCV) nonstructural 5A (NS5A) protein have been identified by phenotypic screening campaigns using HCV subgenomic replicons. The demonstration of antiviral activity in HCV-infected subjects by the HCV NS5A replication complex inhibitor (RCI) daclatasvir (1) spawned considerable interest in this mechanistic approach. In this Perspective, we summarize the medicinal chemistry studies that led to the discovery of 1 and other chemotypes for which resistance maps to the NS5A protein and provide synopses of the profiles of many of the compounds currently in clinical trials. We also summarize what is currently known about the NS5A protein and the studies using NS5A RCIs and labeled analogues that are helping to illuminate aspects of both protein function and inhibitor interaction. We conclude with a synopsis of the results of notable clinical trials with HCV NS5A RCIs.
Low-complexity space-time codes for high and low-priority streams (2009)

We examine the design of space-time codes that allow simple encoding and decoding of high and low-priority streams of data. A desirable multi-stream space-time code has the property that accurate soft bit information can be computed easily for one stream without having to decode the remaining streams. This allows, for example, a high-priority stream to be decoded optimally with complexity that is not adversely affected by the presence of a low-priority stream. Conditions that allow simple decoding are provided, and these conditions are demonstrated with some examples. We look specifically at two-stream codes, and compare performance with standard single-antenna hierarchical two-stream methods.
Interleaver design for MIMO-OFDM based wireless LAN (2006)

Tremendous interest in multimedia applications such as wireless video streaming drives the need for high throughput WLAN communications. In this paper, we study the interleaver design for MIMO-OFDM based high throughput WLAN transmission which enjoys higher spatial diversity and frequency diversity. New design metrics are proposed as the design guideline to maximize the diversity, which can avoid exhaustive search for interleaver parameters. Different interleaver schemes are proposed which provide tradeoff between implementation complexity and performance. Extensive simulation results show that our design metrics are effective and robust to different channel models and the new interleaver design can achieve 1.5 - 2 dB system performance improvement compared to legacy interleaver
Real‐time detection and localization of microseismic events (2010)

An automated algorithm has been developed to detect and locate micro‐earthquakes in real‐time which successfully combines model‐ and data‐driven approaches and is applicable to any receiver configuration. The model‐driven approach is used for robust event detection. It additionally provides model arrival times, which serve as good initial estimates of P‐ and S‐wave onset times. Such estimates are subsequently used to accurately measure true arrival times and extract the associated polarization information required for a data‐driven localization method. Accurate hypocenter locations are therefore obtained through a sequential resolution of the constrained inverse problem, addressing the potential convergence issues of a gradient search. In addition to the global processing flow, the method uses a new set of tools for picking arrival times and polarization angles.
Dynamic Data Stability in SRAM Cells and Its Implications on Data Stability Tests (2006)

The paper discusses the concept of dynamic data stability in the SRAM cells. It is shown that the criteria for the absolute static data stability in an SRAM cell is a sub-set of its dynamic data stability. Hence, test methods that are based on dynamic stress of the cell have limited success in discovering the defective cells. Hammer test, for example, fails to discover the faults in an SRAM cell when it is data stable in the dynamic sense but not statically data stable. It will be shown that a long cell access time can detect such faults as it reduces the effect of the dynamic data stability. This method can be combined with stressed cell methods to achieve higher accuracy. Simulation results in a 130nm CMOS technology confirm the method with a good success
Procalcitonin and its Component Peptides in Systemic Inflammation: Immunochemical Characterization (1997)

These studies indicate that ProCT and its component peptides circulate in normal persons. The serum of patients with SIRS/sepsis contains greatly increased levels of ProCT, nProCT and often, CT:CCP-I. However, in this condition, post-translational processing is incomplete, resulting in mature CT levels that are normal or minimally elevated. In contrast, patients with neuroendocrine cancer have considerably high mature CT levels. Interestingly, although serum CGRP levels often are high in neuroendocrine cancer, they are low in SIRS/sepsis. The marked hyperprocalcitonemia of SIRS/sepsis is probably a consequence of the pro-inflammatory cytokine cascade, and appears to be secreted in a constitutive fashion; the cell(s) of origin of this remarkable hypersecretion is unknown. There is a very marked positive correlation between serum levels of ProCT and nProCT, and the lower level of sensitivity for nProCT may make its measurement a more useful marker for early or mild SIRS/sepsis.
Antimicrobial peptides derived from growth factors (2007)

Growth factors, comprising diverse protein and peptide families, are involved in a multitude of developmental processes, including embryogenesis, angiogenesis, and wound healing. Here we show that peptides derived from HB-EGF, amphiregulin, hepatocyte growth factor, PDGF-A and PDGF-B, as well as various FGFs are antimicrobial, demonstrating a previously unknown activity of growth factor-derived peptides. The peptides killed the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis, as well as the fungus Candida albicans. Several peptides were also active against the Gram-positive S. aureus. Electron microscopy analysis of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. Furthermore, HB-EGF was antibacterial per se, and its epitope GKRKKKGKGLGKKRDPCLRKYK retained its activity in presence of physiological salt and plasma. No discernible hemolysis was noted for the growth factor-derived peptides. Besides providing novel templates for design of peptide-based antimicrobials, our findings demonstrate a previously undisclosed link between the family of growth factors and antimicrobial peptides, both of which are induced during tissue remodelling and repair.
Hydrothermal Synthesis of Lithium Manganese Oxide with .ALPHA.-NaFeO2 Structure. (2001)

Hydrothermal synthesis of lithium manganese oxide with α-NaFeO2 structure has been studied. A LixMnO2⋅nH2O, (Li-birnessite), with rhombohedral symmetry was used as a starting material. When the molar ratio of Mn/Al was smaller than 0.9/0.1, spinel type lithium manganese oxides were obtained. On the other hand, when the molar ratio of Mn/Al was larger than 0.85/0.15, metastable lithium manganese oxides with α-NaFeO2 structure formed at 80°C, and the capacity fade of the Li-ion cell with cathodes made of these oxides was very small in comparison with that of cathodes made of layered Li-manganese oxides, as previously reported.
Optimization of broadband quantum cascade lasers for continuous wave operation (2003)

We have optimized the design of the broadband quantum cascade laser for cw operation. The improved design leads to a gain ripple of only about 4 cm−1 over more than a 0.5-μm spectral range. Simultaneous cw emission at several wavelengths spanning the range between 6.7 and 7.4 μm has been achieved in a temperature interval from 20 to 77 K.
Reduction of Campylobacter jejuni colonization of chicks by cecum-colonizing bacteria producing anti-C. jejuni metabolites (1992)

Cecum-colonizing bacteria were isolated from Campylobacter jejuni-free White Leghorn (Gallus domesticus) laying hens and screened for the ability to produce anti-C. jejuni metabolites. Nine isolates were obtained that possessed this characteristic. The peroral administration of the nine isolates as a mixture (ca. 10(9) per chick) to 1-day-old chicks was followed 1 week later by peroral inoculation of Campylobacter jejuni (ca. 10(9) per chick) to determine if the cecal isolates could protect chicks from colonization by campylobacters. The nine-strain mixture of cecal bacteria provided from 41 to 85% protection from C. jejuni colonization. The protective bacteria were reduced to a mixture of three strains on the basis of their ability to utilize mucin as a sole substrate for growth. These strains included Klebsiella pneumoniae 23, Citrobacter diversus 22, and Escherichia coli (O13:H-) 25. Four feeding trials with this three-strain mixture provided from 43 to 100% (average, 78%) protection from C. jejuni colonization. The dominant cecal bacterium of chicks treated with the three-strain mixture was consistently E. coli O13:H-. Similarly, three trials with only E. coli 25 used as the protective bacterium resulted in 49 to 72% (average, 59%) protection from C. jejuni colonization, with E. coli O13:H- being the dominant cecal bacterium in all cases. Although not completely effective, E. coli 25 substantially reduced the incidence of C. jejuni colonization of chicks. For all trials, fewer C. jejuni were present in the ceca of colonized chicks receiving the protective bacteria before exposure to C. jejuni than in chicks receiving only C. jejuni.(ABSTRACT TRUNCATED AT 250 WORDS)
Special acoustical role of pinna simplifying spatial target localization by the brown long-eared bat <i>Plecotus auritus</i> (2020)

Echolocating bats locate a target by sonar. The performance of this system is related to the shape of the binaural conformation in bats. From numerical predictions, it was found that in a central frequency band, the orientation of a strong sidelobe is shifted nearly linearly in the vertical direction. Inspired by this, the authors built an accurate wide-scope elevation estimation system by constructing a pair of erect artificial pinnae and realized simultaneous elevation and azimuth estimation by constructing a pair of orthogonal pinnae. By demonstrating the simplicity of spatial target echolocation, the authors showed that only two independent single-output neural networks were needed for either elevation or azimuth estimation. This method could be applied to imitate any other mammal species with similar pinna directivity patterns to facilitate and improve an artificial echolocation system.
General Description of the Most Important Medicinal Higher Basidiomycetes Mushrooms. 1. (1999)

This article contains detailed general mycological information on a number of universally recognized and medicinally valuable higher Basidiomycetes mushrooms: Auricularia auricula-judae (L. :Fr.) Wettst., Tremella fuciformis Berk., T. mesenterica Retz.: Fr., Ganoderma lucidum (Curt.: Fr.) P. Karst., Pleurotus ostreatus (Jacq.: Fr.) Kumm., P. pulmonarius (Fr.: Fr.) Quel. (=P. sajorcaju), and Lentinus edodes (Berk.) Sing. Their biological and ethnomycological properties, taxonomy, morphology, anatomy, description, cultural characteristics, distribution, critical notes, and some medicinal properties are presented. Selected literature is cited on all seven species.
Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice (2019)

Takeda G protein-coupled receptor 5 (TGR5) agonists induce systemic release of glucagon-like peptides (GLPs) from intestinal L cells, a potentially therapeutic action against metabolic diseases such as nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), and Type 2 diabetes. Historically, TGR5 agonist use has been hindered by side effects, including inhibition of gallbladder emptying. Here, we characterize RDX8940, a novel, orally administered TGR5 agonist designed to have minimal systemic effects and investigate its activity in mice fed a Western diet, a model of NAFLD and mild insulin resistance. Agonist activity, binding selectivity, toxicity, solubility, and permeability of RDX8940 were characterized in standard in vitro models. RDX8940 pharmacokinetics and effects on GLP secretion, insulin sensitivity, and liver steatosis were assessed in C57BL/6 mice fed normal or Western diet chow and given single or repeated doses of RDX8940 or vehicle, with or without dipeptidyl peptidase-4 (DPP4) inhibitors. Gallbladder effects were assessed in CD-1 mice fed normal chow and given RDX8940 or a systemic TGR5 agonist or vehicle. Our results showed that RDX8940 is minimally systemic, potent, and selective, and induces incretin (GLP-1, GLP-2, and peptide YY) secretion. RDX8940-induced increases in plasma active GLP-1 (aGLP-1) levels were enhanced by repeated dosing and by coadministration of DPP4 inhibitors. RDX8940 increased hepatic exposure to aGLP-1 without requiring coadministration of a DPP4 inhibitor. In mice fed a Western diet, RDX8940 improved liver steatosis and insulin sensitivity. Unlike systemic TGR5 agonists, RDX8940 did not inhibit gallbladder emptying. These results indicate that RDX8940 may have therapeutic potential in patients with NAFLD/NASH. NEW & NOTEWORTHY Takeda G protein-coupled receptor 5 (TGR5) agonists have potential as a treatment for nonalcoholic steatohepatitis and nonalcoholic fatty liver disease (NAFLD) but have until now been associated with undesirable side effects associated with systemic TGR5 agonism, including blockade of gallbladder emptying. We demonstrate that RDX8940, a potent, selective, minimally systemic oral TGR5 agonist, improves liver steatosis and insulin sensitivity in a mouse model of NAFLD and does not inhibit gallbladder emptying in mice.
Identification of type-specific linear epitopes in the glycoproteins gp46 and gp21 of human T-cell leukemia viruses type I and type II using synthetic peptides. (1991)

Synthetic peptides of 20-25 amino acids were employed in enzyme-linked immunosorbent assays to identify linear epitopes in the external glycoprotein gp46 and the transmembrane glycoprotein gp21 of human T-cell leukemia/lymphotropic viruses type I (HTLV-I) and II (HTLV-II). Ten linear epitopes were identified in the HTLV-I glycoproteins, seven in gp46 and three in gp21. Three major linear epitopes were identified in the gp46 of HTLV-II. Peptides representing linear epitopes of gp46 were found to be sensitive and specific for the detection of antibody and permit serological identification and differentiation of HTLV-I and HTLV-II infections.
Neuromorphic Computing – From Materials Research to Systems Architecture Roundtable (2015)

Computation in its many forms is the engine that fuels our modern civilization. Modern computation—based on the von Neumann architecture—has allowed, until now, the development of continuous improvements, as predicted by Moore’s law. However, computation using current architectures and materials will inevitably—within the next 10 years—reach a limit because of fundamental scientific reasons. DOE convened a roundtable of experts in neuromorphic computing systems, materials science, and computer science in Washington on October 29-30, 2015 to address the following basic questions: Can brain-like (“neuromorphic”) computing devices based on new material concepts and systems be developed to dramatically outperform conventional CMOS based technology? If so, what are the basic research challenges for materials sicence and computing? The overarching answer that emerged was: The development of novel functional materials and devices incorporated into unique architectures will allow a revolutionary technological leap toward the implementation of a fully “neuromorphic” computer. To address this challenge, the following issues were considered: The main differences between neuromorphic and conventional computing as related to: signaling models, timing/clock, non-volatile memory, architecture, fault tolerance, integrated memory and compute, noise tolerance, analog vs. digital, and in situ learning New neuromorphic architectures needed to: produce lower energy consumption, potential novel nanostructured materials, and enhanced computation Device and materials properties needed to implement functions such as: hysteresis, stability, and fault tolerance Comparisons of different implementations: spin torque, memristors, resistive switching, phase change, and optical schemes for enhanced breakthroughs in performance, cost, fault tolerance, and/or manufacturability.
The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome (2021)

Neurogenesis impairment is a key determinant of intellectual disability in Down syndrome (DS), a genetic pathology due to triplication of chromosome 21. Since neurogenesis ceases after birth, apart in the hippocampus and olfactory bulb, the only means to tackle the problem of neurogenesis impairment in DS at its root is to intervene during gestation. A few studies in DS mouse models show that this is possible, although the drugs used may raise caveats in terms of safety. We previously found that neonatal treatment with 7,8-dihydroxyflavone (7,8-DHF), a flavonoid present in plants, restores hippocampal neurogenesis in the Ts65Dn model of DS. The goal of the current study was to establish whether prenatal treatment with 7,8-DHF improves/restores overall brain proliferation potency. Pregnant Ts65Dn females received 7,8-DHF from embryonic day 10 until delivery. On postnatal day 2 (P2) the pups were injected with BrdU and were killed after either 2 h or 52-60 days (P52-60). Evaluation of the number of proliferating (BrdU+) cells in various forebrain neurogenic niches of P2 mice showed that in treated Ts65Dn mice proliferation potency was improved or even restored in most of the examined regions, including the hippocampus. Quantification of the surviving BrdU+ cells in the dentate gyrus of P52-60 mice showed no difference between treated and untreated Ts65Dn mice. At P52-60, however, treated Ts65Dn mice exhibited a larger number of granule cells in comparison with their untreated counterparts, although their number did not reach that of euploid mice. Results show that 7,8-DHF has a widespread impact on prenatal proliferation potency in Ts65Dn mice and exerts mild long-term effects. It remains to be established whether treatment extending into the neonatal period can lead to an improvement in brain development that is retained in adulthood.
Kinetic Study of the Homogeneous Atom Transfer Radical Polymerization of Methyl Methacrylate (1997)

The homogeneous controlled/“living” radical polymerization of methyl methacrylate (MMA) using the atom transfer radical polymerization (ATRP) with CuCl/4,4‘-di(5-nonyl)-2,2‘-bipyridine catalytic system and diphenyl ether as the solvent generated well-defined polymers with polydispersities Mw/Mn ≤ 1.2. The evolution of the molecular weights of the polymers follows the ratio of the mass of the consumed monomer to the initial initiator concentration. The rate of polymerization follows first-order kinetics with respect to the decrease of monomer concentration. The polymerization rate reaches a maximum when the ratio of ligand-to-CuICl is one-to-one. ATRP of MMA shows first-order kinetics with respect to both CuICl and the initiator, alkyl or sulfonyl chloride. The rate of polymerization did not obey simple negative first-order kinetics with respect to the concentration of CuIICl, partially due to a persistent radical effect, which resulted in the increase of [CuIICl] in the initial stage of polymerization. Thermodynamic data and activation parameters for the solution ATRP of MMA are reported.
Isolation of Alcohol Oxidase and Two Other Methanol Regulatable Genes from the Yeast <i>Pichia pastoris</i> (1985)

The oxidation of methanol follows a well-defined pathway and is similar for several methylotrophic yeasts. The use of methanol as the sole carbon source for the growth of Pichia pastoris stimulates the expression of a family of genes. Three methanol-responsive genes have been isolated; cDNA copies have been made from mRNAs of these genes, and the protein products from in vitro translations have been examined. The identification of alcohol oxidase as one of the cloned, methanol-regulated genes has been made by enzymatic, immunological, and sequence analyses. Methanol-regulated expression of each of these three isolated genes can be demonstrated to occur at the level of transcription. Finally, DNA subfragments of two of the methanol-responsive genomic clones from P. pastoris have been isolated and tentatively identified as containing the control regions involved in methanol regulation.
Analysis of 8 Sarcomeric Candidate Genes for Feline Hypertrophic Cardiomyopathy Mutations in Cats with Hypertrophic Cardiomyopathy (2009)

Mutations within these cardiac genes do not appear to be the only cause of HCM in these breeds. Evaluation of additional cardiac genes is warranted to identify additional molecular causes of this feline cardiac disease.