gebhart/patrepeval huggingface dataset:
Stress-Based Identification and Classification of Antibacterial Agents: Second-Generation Escherichia coli Reporter Strains and Optimization of Detection (2002)

Escherichia coli strains bearing single-copy fusions between the lacZ reporter gene and the cspA, ibp, or P3rpoH stress promoters offer a simple means to detect sublethal concentrations of antibacterial agents interfering with prokaryotic translation or cell envelope integrity while simultaneously providing information on the mechanism of action of the test compound (A. A. Bianchi and F. Baneyx, Appl. Environ. Microbiol. 65:5023-5027, 1999). Here, we expand the usefulness of this system by (i) demonstrating that a fusion between the SOS-inducible sulA promoter and lacZ is a highly specific probe for the detection of antimicrobial agents that ultimately interfere with DNA replication, (ii) showing that inactivation of the tolC gene allows efficient detection of very low concentrations of model antibiotics (including aminoglycosides) whereas polymyxin B-mediated outer membrane permeabilization facilitates the identification of intermediate concentrations of hydrophobic compounds, and (iii) validating the potential of detector strains and sensitization strategies for high-throughput screening using a reproducible and internally consistent 96-well microplate assay.
SULFURIC ACID INDUSTRY AND MARKET ANALYSIS (2000)

In this paper, the output and consumption of sulfuric acid both at home and abroad are briefly described with the emphasis on the import and export as well as the demand for sulfuric acid and materials for producing it in China. In addition, prediction and analysis on the trends of production and consumption of sulfuric acid in the future are provided, and some constructive comments presented.
Voltage-gated K+ channel beta subunits: expression and distribution of Kv beta 1 and Kv beta 2 in adult rat brain. (1996)

Recent cloning of K(+) channel β subunits revealed that these cytoplasmic polypeptides can dramatically alter the kinetics of current inactivation and promote efficient glycosylation and surface expression of the channel-forming α subunits. Here, we examined the expression, distribution, and association of two of these β subunits, Kvβ1 and Kvβ2, in adult rat brain. In situhybridization using cRNA probes revealed that these β-subunit genes are heterogeneously expressed, with high densities of Kvβ1 mRNA in the striatum, CA1 subfield of the hippocampus, and cerebellar Purkinje cells, and high densities of Kvβ2 mRNA in the cerebral cortex, cerebellum, and brainstem. Immunohistochemical staining using subunit-specific monoclonal and affinity-purified polyclonal antibodies revealed that the Kvβ1 and Kvβ2 polypeptides frequently co-localize and are concentrated in neuronal perikarya, dendrites, and terminal fields, and in the juxtaparanodal region of myelinated axons. Immunoblot and reciprocal co-immunoprecipitation analyses indicated that Kvβ2 is the major β subunit present in rat brain membranes, and that most K(+) channel complexes containing Kvβ1 also contain Kvβ2. Taken together, these data suggest that Kvβ2 is a component of almost all K(+)channel complexes containing Kv1 α subunits, and that individual channels may contain two or more biochemically and functionally distinct β-subunit polypeptides.
Carbene complexes of iron, molybdenum, and ruthenium: a new route to metal–carbene derivatives (1971)

The acyl derivatives M–Ac, where M =(π-C5H5)Fe(CO)P(Hex)3, (π-C5H5)Mo(CO)2P(Hex)3, (π-C5H5)Ru(CO)2(π-C5H5)Ru(CO)PPh3, or (π-C5H5)Ru(CO)P(Hex)3 have been prepared. Treatment of these with acids H+A– A = Cl or BF4, or with trialkyloxonium salts, R3O+BF4–, R = Me or Et, forms salts of the corresponding carbene derivatives, [M = C(OR′)Me]+ A–, R′= H or alkyl. The hydroxy-carbenes react with diazomethane forming the methyl analogues, R′= Me. Treatment of the carbene [(π-C5H5)Fe(CO)(PPh3){C(OEt)Me}]+BF4– with sodium borohydride forms the π-ethoxyethyl derivative (π-C5H5)Fe(CO)(PPh3){CH(OEt)Me}, and with lithium methyl, propane, propene and the acyl derivative, (π-C5H5)Fe(CO)(PPh3)(Ac) are formed.
A More Complex Isoleucine Aptamer with a Cognate Triplet (2005)

The simplest RNA that can meet a column affinity selection for isoleucine was previously defined using selection amplification with decreasing numbers of randomized nucleotides. This simplest UAUU motif was a small asymmetric internal loop. Conserved positions of the loop include isoleucine codon and anticodon triplets (Lozupone C., Changayil, S., Majerfeld, I., and Yarus, M. (2003) RNA (N. Y.) 9, 1315-1322). Using new primer sequences, we now select a somewhat more complex isoleucine binding RNA, requiring 4.7 more bits of information to describe. The newly selected structure is a terminal or hairpin loop of 20 nucleotides, 15 being invariant. An information profile shows that the new binding site contains five short functional loop regions joined by less significant single nucleotide positions. Among the important nucleotides is a conserved isoleucine anticodon, supporting the escaped triplet theory, which posits a stereochemical genetic code originating in RNA amino acid binding sites.
Two dimensional magnetic manipulation of microdroplets on a chip (2005)

In this paper we describe the two-dimensional (2D) magnetic manipulation of aqueous droplets suspended in silicone oil over the chip surface. The magnetic actuation is based on the force imposed on superparamagnetic microparticles inside the droplets. These can be displaced, merged, mixed and separated by changing the topology of the magnetic field created by a multilayer set of coils. The magnetic manipulation forces are generated on our chip without the use of external moving magnets. Our results demonstrate the potential of the proposed system in droplet-based biomedical analysis methods on a chip.
Purification, priming, and catalytic acylation of carrier protein domains in the polyketide synthase and nonribosomal peptidyl synthetase modules of the HMWP1 subunit of yersiniabactin synthetase (2000)

The 207-kDa polyketide synthase (PKS) module (residues 1-1895) and the 143-kDa nonribosomal peptidyl synthetase (NRPS) module (1896-3163) of the 350-kDa HMWP1 subunit of yersiniabactin synthetase have been expressed in and purified from Escherichia coli in soluble forms to characterize the acyl carrier protein (ACP) domain of the PKS module and the homologous peptidyl carrier protein (PCP(3)) domain of the NRPS module. The apo-ACP and PCP domains could be selectively posttranslationally primed by the E. coli ACPS and EntD phosphopantetheinyl transferases (PPTases), respectively, whereas the Bacillus subtilis PPTase Sfp primed both carrier protein domains in vitro or during in vivo coexpression. The holo-NRPS module but not the holo-PKS module was then selectively aminoacylated with cysteine by the adenylation domain embedded in the HMWP2 subunit of yersiniabactin synthetase, acting in trans. When the acyltransferase (AT) domain of HMWP1 was analyzed for its ability to malonylate the holo carrier protein domains, in cis acylation was first detected. Then, in trans malonylation of the excised holo-ACP or holo-PCP(3)-TE fragments by HMWP1 showed both were malonylated with a 3:1 catalytic efficiency ratio, showing a promiscuity to the AT domain.
Serum and cerebrospinal fluid enzymes in subarachnoid haemorrhage (1989)

Serum levels of creatine kinase (CK) and its isoenzyme CK-MB, lactate dehydrogenase (LDH), hydroxybutyric dehydrogenase (HBDH), glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were studied in 50 patients with subarachnoid haemorrhage. In 18 cases the cerebrospinal fluid (CSF) was also examined for total concentration of CK and CK-MB. The results were correlated with the degree of neurological deterioration, the angiographic spasm and prognosis. Concurrent increase of CK-MB, LDH and HBDH serum levels indicates a poor prognosis, whereas increase of GOT and GPT does not have clinical significance. High CK-MB levels in CSF were associated with the worst clinical evolution. However, increase of serum enzymes coincided in most cases with the appearance of the spasm. Monitoring of CK-MB, LDH and HBDH serum levels can be useful for following the evolution of the spasm and in predicting the outcome for patients with subarachnoid haemorrhage.
Myoediting: Toward Prevention of Muscular Dystrophy by Therapeutic Genome Editing (2018)

Muscular dystrophies represent a large group of genetic disorders that significantly impair quality of life and often progress to premature death. There is no effective treatment for these debilitating diseases. Most therapies, developed to date, focus on alleviating the symptoms or targeting the secondary effects, while the underlying gene mutation is still present in the human genome. The discovery and application of programmable nucleases for site-specific DNA double-stranded breaks provides a powerful tool for precise genome engineering. In particular, the CRISPR/Cas system has revolutionized the genome editing field and is providing a new path for disease treatment by targeting the disease-causing genetic mutations. In this review, we provide a historical overview of genome-editing technologies, summarize the most recent advances, and discuss potential strategies and challenges for permanently correcting genetic mutations that cause muscular dystrophies.
Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre‐clinical AD, amnestic mild cognitive impairment and late‐stage AD (2015)

The clinical symptoms of Alzheimer disease (AD) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis. The current study investigated the status of the PI3K/Akt/mTOR pathway in post-mortem tissue from the inferior parietal lobule (IPL) at three different stages of AD: late AD, amnestic mild cognitive impairment (MCI) and pre-clinical AD (PCAD). Our findings suggest that the alteration of mTOR signaling and autophagy occurs at early stages of AD. We found a significant increase in Aβ (1-42) levels, associated with reduction in autophagy (Beclin-1 and LC-3) observed in PCAD, MCI, and AD subjects. Related to the autophagy impairment, we found a hyperactivation of PI3K/Akt/mTOR pathway in IPL of MCI and AD subjects, but not in PCAD, along with a significant decrease in phosphatase and tensin homolog. An increase in two mTOR downstream targets, p70S6K and 4EBP1, occurred in AD and MCI subjects. Both AD and MCI subjects showed increased, insulin receptor substrate 1, a candidate biomarker of brain insulin resistance, and GSK-3β, a kinase targeting tau phosphorylation. Nevertheless, tau phosphorylation was increased in the clinical groups. The results hint at a link between Aβ and the PI3K/Akt/mTOR axis and provide further insights into the relationship between AD pathology and insulin resistance. In addition, we speculate that the alteration of mTOR signaling in the IPL of AD and MCI subjects, but not in PCAD, is due to the lack of substantial increase in oxidative stress. The figure represents the three different stages of Alzheimer Disease: Preclinical Alzheimer Disease (PCAD), Mild cognitive impairment (MCI) and late stage of Alzheimer Disease. The progression of the disease is associated with a reduction in autophagy (Beclin-1 and LC-3) observed in Inferior parietal lobe of PCAD, MCI, and AD subjects (light red). Related to the autophagy impairment, the graph shows the impairment of PI3K/Akt/mTOR in MCI and AD subjects (dark red).
Profiling the NIH Small Molecule Repository for Compounds That Generate H 2 O 2 by Redox Cycling in Reducing Environments (2010)

We have screened the Library of Pharmacologically Active Compounds (LOPAC) and the National Institutes of Health (NIH) Small Molecule Repository (SMR) libraries in a horseradish peroxidase-phenol red (HRP-PR) H2O2 detection assay to identify redox cycling compounds (RCCs) capable of generating H2O2 in buffers containing dithiothreitol (DTT). Two RCCs were identified in the LOPAC set, the ortho-naphthoquinone beta-lapachone and the para-naphthoquinone NSC 95397. Thirty-seven (0.02%) concentration-dependent RCCs were identified from 195,826 compounds in the NIH SMR library; 3 singleton structures, 9 ortho-quinones, 2 para-quinones, 4 pyrimidotriazinediones, 15 arylsulfonamides, 2 nitrothiophene-2-carboxylates, and 2 tolyl hydrazides. Sixty percent of the ortho-quinones and 80% of the pyrimidotriazinediones in the library were confirmed as RCCs. In contrast, only 3.9% of the para-quinones were confirmed as RCCs. Fifteen of the 251 arylsulfonamides in the library were confirmed as RCCs, and since we screened 17,868 compounds with a sulfonamide functional group we conclude that the redox cycling activity of the arylsulfonamide RCCs is due to peripheral reactive enone, aromatic, or heterocyclic functions. Cross-target queries of the University of Pittsburgh Drug Discovery Institute (UPDDI) and PubChem databases revealed that the RCCs exhibited promiscuous bioactivity profiles and have populated both screening databases with significantly higher numbers of active flags than non-RCCs. RCCs were promiscuously active against protein targets known to be susceptible to oxidation, but were also active in cell growth inhibition assays, and against other targets thought to be insensitive to oxidation. Profiling compound libraries or the hits from screening campaigns in the HRP-PR H(2)O(2) detection assay significantly reduce the timelines and resources required to identify and eliminate promiscuous nuisance RCCs from the candidates for lead optimization.
Extreme CD8 T Cell Requirements for Anti-Malarial Liver-Stage Immunity following Immunization with Radiation Attenuated Sporozoites (2010)

Radiation-attenuated Plasmodium sporozoites (RAS) are the only vaccine shown to induce sterilizing protection against malaria in both humans and rodents. Importantly, these "whole-parasite" vaccines are currently under evaluation in human clinical trials. Studies with inbred mice reveal that RAS-induced CD8 T cells targeting liver-stage parasites are critical for protection. However, the paucity of defined T cell epitopes for these parasites has precluded precise understanding of the specific characteristics of RAS-induced protective CD8 T cell responses. Thus, it is not known whether quantitative or qualitative differences in RAS-induced CD8 T cell responses underlie the relative resistance or susceptibility of immune inbred mice to sporozoite challenge. Moreover, whether extraordinarily large CD8 T cell responses are generated and required for protection following RAS immunization, as has been described for CD8 T cell responses following single-antigen subunit vaccination, remains unknown. Here, we used surrogate T cell activation markers to identify and track whole-parasite, RAS-vaccine-induced effector and memory CD8 T cell responses. Our data show that the differential susceptibility of RAS-immune inbred mouse strains to Plasmodium berghei or P. yoelii sporozoite challenge does not result from host- or parasite-specific decreases in the CD8 T cell response. Moreover, the surrogate activation marker approach allowed us for the first time to evaluate CD8 T cell responses and protective immunity following RAS-immunization in outbred hosts. Importantly, we show that compared to a protective subunit vaccine that elicits a CD8 T cell response to a single epitope, diversifying the targeted antigens through whole-parasite RAS immunization only minimally, if at all, reduced the numerical requirements for memory CD8 T cell-mediated protection. Thus, our studies reveal that extremely high frequencies of RAS-induced memory CD8 T cells are required, but may not suffice, for sterilizing anti-Plasmodial immunity. These data provide new insights into protective CD8 T cell responses elicited by RAS-immunization in genetically diverse hosts, information with relevance to developing attenuated whole-parasite vaccines.
Optimizing platelet inhibition (2008)

The platelet P2Y12 receptor plays a critical role in sustaining ADP-mediated platelet aggregation. Drawbacks of the thienopyridine clopidogrel, a prodrug of an irreversible P2Y12 antagonist, include the need for two-step metabolism to its active form and partial hydrolysis to its inactive metabolite. Both contribute to high variability in the degree of platelet inhibition and the irreversibility of binding complicates both acute and planned invasive treatments when rapid offset of antiplatelet activity is desired. Novel P2Y12 antagonists include the thienopyridine prasugrel and the selective, direct, reversible antagonists cangrelor (iv) and AZD6140 (oral). Prasugrel, also an irreversible antagonist, requires only one-step metabolism to active form and achieves greater inhibition of platelet aggregation (IPA) than clopidogrel. Recently published data indicate that this translates into improved efficacy. Like clopidogrel, prasugrel relies on new platelet generation for offset of effect. The direct reversible antagonists bind directly to the receptor, and the degree of IPA closely follows plasma drug concentrations. In addition to permitting more rapid offset of effect and greater and more consistent IPA than clopidogrel, direct reversible antagonists may exert additional beneficial effects via blockade of P2Y12 in vascular smooth muscle cells. Reversible antagonists also appear to exhibit a wider therapeutic window, showing reduced bleeding time prolongation per given degree of antithrombotic effect in experimental models. Ongoing large-scale Phase 3 clinical trials are examining cangrelor in patients with acute coronary syndromes (ACS) also undergoing percutaneous coronary intervention (PCI) and AZD6140 in ACS patients being treated with medical therapy, PCI, or coronary artery bypass grafting.
Direct Observation of the Local-Field-Enhanced Surface Photochemical Reactions (1983)

The enhancement of photochemical reactions on surface-supported metallic particles is reported. The result is obtained by uv photodissociation of organometallic molecules adsorbed on the supporting surface. Transmission electron-microscope micrographs of the resulting photodeposited film reveal enhanced deposition on and near the metal particles, and a clear interference pattern resulting from the mixing of the incident and reradiated light. The importance of the particle plasma resonance is described.
Computing Issues for Big Data (2014)

Big data may contain big values, but also brings lots of challenges to the computing theory, architecture, framework, knowledge discovery algorithms, and domain specific tools and applications. Beyond the 4-V or 5-V characters of big datasets, the data processing shows the features like inexact, incremental, and inductive manner. This brings new research opportunities to research community across theory, systems, algorithms, and applications. Is there some new "theory" for the big data? How to handle the data computing algorithms in an operatable manner? This report shares some view on new challenges identified, and covers some of the application scenarios such as micro-blog data analysis and data processing in building next generation search engines.
Antigen-induced Acute and Late-phase Responses in Primates (1992)

We have examined the proinflammatory cell influx as well as the levels of eosinophil and neutrophil-derived granule proteins in BAL fluid obtained from monkeys undergoing acute and late-phase (dual) or single acute bronchoconstriction following antigen inhalation. Prior to antigen inhalation, there was a significantly higher number (and percentage) of eosinophils in BAL fluid from dual responder monkeys as compared with single responders. The late-phase response (LPR) (6 to 8 h postantigen) was associated with a decrease in the number of BAL eosinophils and an increase in the levels of BAL fluid EPO that returned to baseline levels by 24 h postantigen inhalation. In contrast, the number of BAL neutrophils prior to antigen inhalation were low. Concurrent with the LPR, the number of BAL neutrophils and the concentration of EPO in BAL fluid were significantly increased above that occurring in single responders. Chronic treatment (7 days) with dexamethasone significantly reduced the number of BAL eosinophils and the BAL levels of EPO prior to antigen inhalation in dual responder (LPR) monkeys and significantly blocked the dual response and both the associated neutrophil influx into the airways and an increase in BAL fluid EPO during the LPR. We conclude that, in this primate model, eosinophil activation and a large influx of neutrophils into the airways is associated with the occurrence of the antigen-induced late-phase airway obstructive response.
Characterization of Lewis antigens in normal colon and gastrointestinal adenocarcinomas. (1985)

The Lewis a antigen (Lea)- and Lewis b antigen (Leb)-active glycolipids and glycoproteins in normal colon mucosa, colon carcinoma tumors, and gastrointestinal tumor cell lines were studied by using monoclonal antibodies against Lewis determinants in solid-phase radioimmunoassay, chromatogram binding assay, and immunoprecipitation/PAGE. Lea-5 was a major component of the purified non-acid glycolipid fraction from normal colon mucosas from four patients examined and Lea-7 was a minor component in three of these four cases. Lea in colon carcinoma of the same patients was expressed as Lea-5 in all four cases and as both Lea-5 and Lea-7 in one of the four cases. All normal colon mucosa samples expressed Lea but not Leb. Leb-6 was expressed in all tumors obtained from the same patients as normal colon mucosa (Leb negative) samples and in the gastrointestinal tumor cell lines. These findings indicate that Leb is a colon adenocarcinoma-associated antigen and that Lea and Leb are coexpressed in tumor tissue. Evidence is presented for the coexistence of Lea and Leb carbohydrate determinants in both glycolipid and glycoprotein forms in the same cells.
DEEP BRAIN STIMULATION FOR OBSESSIVE-COMPULSIVE DISORDER (2007)

High-frequency stimulation via a lead placed in the anterior limb of the internal capsule induced widespread hemodynamic changes at both the cortical and subcortical levels including areas typically associated with the pathogenesis of obsessive-compulsive disorder.