gebhart/patrepeval huggingface dataset:
Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions (2001)

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes motor, sensory, and cognitive deficits. The present study characterized demyelinated lesions in the cerebral cortex of MS patients. One hundred twelve cortical lesions were identified in 110 tissue blocks from 50 MS patients. Three patterns of cortical demyelination were identified: Type I lesions were contiguous with subcortical white matter lesions; Type II lesions were small, confined to the cortex, and often perivascular; Type III lesions extended from the pial surface to cortical layer 3 or 4. Inflammation and neuronal pathology were studied in tissue from 8 and 7 patients, respectively. Compared to white matter lesions, cortical lesions contained 13 times fewer CD3-positive lymphocytes (195 vs 2,596/mm3 of tissue) and 6 times fewer CD68-positive microglia/macrophages (11,948 vs 67,956/mm3 of tissue). Transected neurites (both axons and dendrites) occurred at a density of 4,119/mm3 in active cortical lesions, 1,107/mm3 in chronic active cortical lesions, 25/mm3 in chronic inactive cortical lesions, 8/mm3 in myelinated MS cortex, and 1/mm3 in control cortex. In active and chronic active cortical lesions, activated microglia closely apposed and ensheathed apical dendrites, neurites, and neuronal perikarya. In addition, apoptotic neurons were increased significantly in demyelinated cortex compared to myelinated cortex. These data support the hypothesis that demyelination, axonal transection, dendritic transection, and apoptotic loss of neurons in the cerebral cortex contribute to neurological dysfunction in MS patients.
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2 (2009)

The mammalian target of rapamycin (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals. These signaling functions are distributed between at least two distinct mTOR protein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to the selective inhibitor rapamycin and activated by growth factor stimulation via the canonical phosphoinositide 3-kinase (PI3K)-->Akt-->mTOR pathway. Activated mTORC1 kinase up-regulates protein synthesis by phosphorylating key regulators of mRNA translation. By contrast, mTORC2 is resistant to rapamycin. Genetic studies have suggested that mTORC2 may phosphorylate Akt at S473, one of two phosphorylation sites required for Akt activation; this has been controversial, in part because RNA interference and gene knockouts produce distinct Akt phospho-isoforms. The central role of mTOR in controlling key cellular growth and survival pathways has sparked interest in discovering mTOR inhibitors that bind to the ATP site and therefore target both mTORC2 and mTORC1. We investigated mTOR signaling in cells and animals with two novel and specific mTOR kinase domain inhibitors (TORKinibs). Unlike rapamycin, these TORKinibs (PP242 and PP30) inhibit mTORC2, and we use them to show that pharmacological inhibition of mTOR blocks the phosphorylation of Akt at S473 and prevents its full activation. Furthermore, we show that TORKinibs inhibit proliferation of primary cells more completely than rapamycin. Surprisingly, we find that mTORC2 is not the basis for this enhanced activity, and we show that the TORKinib PP242 is a more effective mTORC1 inhibitor than rapamycin. Importantly, at the molecular level, PP242 inhibits cap-dependent translation under conditions in which rapamycin has no effect. Our findings identify new functional features of mTORC1 that are resistant to rapamycin but are effectively targeted by TORKinibs. These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease.
Characteristics of Humic Substances and Their Removal Behavior in Water Treatment (1988)

The characteristics of naturally occurring aquatic humic substances and their removal behavior in water treatment were investigated in a plant operation and in alum coagulation with conventional laboratory jar-test experiments. Specific characteristics of humic substances affected the performance of alum coagulation in removing both humic substances and turbidity. Up to 50% of the humic substances were removed in both the treatment plant and alum coagulation. High-molecular-weight humic substances were preferentially removed. This preference resulted in substantial decreases in color intensity and trihalomethane formation potential per unit mass of humic substances. The characteristics and removal behavior by alum coagulation of commercial humic acid were significantly different from those of the source-water humic substances.
Crystallization and preliminary X‐ray diffraction study of the green flavoenzyme 5‐Hydroxyvaleryl‐CoA dehydratase/dehydrogenase from Clostridium aminovalericum (1994)

The bifunctional flavoenzyme 5-hydroxyvaleryl-CoA dehydratase/dehydrogenase has been crystallized from solutions containing ammonium sulfate (form I) or polyethylene glycol (form II) as precipitant. In both cases, the crystals grew in the monoclinic space group C2. The unit cell dimensions for form I crystals were determined as a = 162.8 A, b = 71.8 A, c = 83.5 A, beta = 109.1 degrees; corresponding values for form II crystals were a = 161.2 A, b = 71.6 A, c = 82.2 A, beta = 109.3 degrees. In both cases most probably there are two monomers per asymmetric unit. The crystals diffract to about 2 A resolution and are rather stable in the X-ray beam.
Flint Sickle-blades of the Late Protohistoric and Early Historic Periods in Israel (1982)

Although the analysis of lithic implements in the proto historic and early historic periods in the Levant has usually been relegated to appendices of monographs or to footnotes in reports, the study of these implements can make a genuine contribution to the archaeology of these periods. The typology of flint sickle blades presented below is intended to establish the basic chronology of sickle types, and hopefully to eliminate some of the confusion in the literature regarding the lifespan of various types. As with ceramics, different lithic types correspond to different regions and periods, and their changing attributes (similar, for example, to the development of ledge handles in ceramics) are also of significance.
Repression of bovine papillomavirus type 1 transcription by the E1 replication protein (1993)

Bovine papillomavirus type 1 (BPV-1) is the prototype virus for the study of papillomavirus gene regulation. The functions of the BPV-1 E2 proteins in transcriptional regulation have been well characterized. The BPV-1 E1 protein is required for viral DNA replication and can bind to the origin of replication alone or in a complex with the E2 transactivator protein. In this study, we demonstrated that the BPV-1 E1 protein is also involved in transcriptional regulation. The E1 protein significantly repressed E2-transactivated transcription from the major early promoter P89. This activity is consistent with the elevated level of P89 transcription observed in BPV-1 E1 open reading frame mutants. Transcriptional repression by E1 correlated with the ability of an E1-E2 protein complex to bind the replication origin but was not dependent on viral DNA replication. These studies identify a new mechanism involved in the regulation of papillomavirus transcription which has implications regarding expression of the viral transforming functions.
Electrophilic Displacement Reactions. IX. Effects of Substituents on Rates of Reactions between Hydrogen Peroxide and Benzeneboronic Acid1-3 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrophilic Displacement Reactions. IX. Effects of Substituents on Rates of Reactions between Hydrogen Peroxide and Benzeneboronic Acid1-3Henry G. Kuivila and Albert G. ArmourCite this: J. Am. Chem. Soc. 1957, 79, 21, 5659–5662Publication Date (Print):November 1, 1957Publication History Published online1 May 2002Published inissue 1 November 1957https://pubs.acs.org/doi/10.1021/ja01578a020https://doi.org/10.1021/ja01578a020research-articleACS PublicationsRequest reuse permissionsArticle Views1837Altmetric-Citations142LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Low-temperature synthesis, structure, and bioactivity of gel-derived glasses in the binary CaO-SiO2 system (2000)

Glasses in the binary system CaO-SiO2 for which the molar fraction of CaO is 0 < or = x < or = 0.50, were prepared by means of a sol-gel route starting from tetraethylorthosilicate and calcium nitrate. The textural features of the monoliths obtained were characterized using N2 gas adsorption, helium ultrapycnometry, and mercury porosimetry. In vitro bioactivity tests were performed in simulated body fluid (SBF). The ionic concentration of the SBF after glass immersion was analyzed using inductively coupled plasma atomic emission spectroscopy. The surfaces of the specimens were characterized using X-ray diffraction and scanning electron microscopy coupled with energy dispersive X-ray analysis before and after in vitro testing. The textural characterization revealed that the glasses were mesoporous with cylindrical pores with average diameters ranging from 25 to 663 A depending on the molar fraction of CaO. The in vitro studies showed that all binary CaO-SiO2 gel-glass compositions produced were bioactive. These results indicate that the binary gel-derived CaO-SiO2 system exhibits a level of bioactivity over a similar molar range of SiO2 content as the previously studied ternary CaO-P2O5-SiO2 system.
A Multichannel MMSE-Based Framework for Speech Source Separation and Noise Reduction (2013)

We propose a new framework for joint multichannel speech source separation and acoustic noise reduction. In this framework, we start by formulating the minimum-mean-square error (MMSE)-based solution in the context of multiple simultaneous speakers and background noise, and outline the importance of the estimation of the activities of the speakers. The latter is accurately achieved by introducing a latent variable that takes N+1 possible discrete states for a mixture of N speech signals plus additive noise. Each state characterizes the dominance of one of the N+1 signals. We determine the posterior probability of this latent variable, and show how it plays a twofold role in the MMSE-based speech enhancement. First, it allows the extraction of the second order statistics of the noise and each of the speech signals from the noisy data. These statistics are needed to formulate the multichannel Wiener-based filters (including the minimum variance distortionless response). Second, it weighs the outputs of these linear filters to shape the spectral contents of the signals' estimates following the associated target speakers' activities. We use the spatial and spectral cues contained in the multichannel recordings of the sound mixtures to compute the posterior probability of this latent variable. The spatial cue is acquired by using the normalized observation vector whose distribution is well approximated by a Gaussian-mixture-like model, while the spectral cue can be captured by using a pre-trained Gaussian mixture model for the log-spectra of speech. The parameters of the investigated models and the speakers' activities (posterior probabilities of the different states of the latent variable) are estimated via expectation maximization. Experimental results including comparisons with the well-known independent component analysis and masking are provided to demonstrate the efficiency of the proposed framework.
A locally conformal finite-difference time-domain (FDTD) algorithm for modeling three-dimensional perfectly conducting objects (1997)

A novel conformal finite-difference time-domain (CFDTD) technique for locally distorted contours that accurately model curved metallic objects is presented in this paper. This approach is easy to implement and is numerically stable. Several examples are presented to demonstrate that the new method yields results that are far more accurate than those generated by the conventional staircasing approach. Example geometries include cylindrical and spherical cavities, and a circular microstrip patch antenna. Accuracy of the scheme is demonstrated by comparing the results derived from analytical and Method of Moments (MoM) techniques.
Hexon Gene Switch Strategy for the Generation of Chimeric Recombinant Adenovirus (2002)

The usefulness of adenovirus as a vehicle for transgene delivery is limited greatly by the induction of neutralizing anti-adenoviral immunity following the initial administration, thereby resulting in shorter-term and reduced levels of transgene expression. In this paper, we outline a strategy for the generation of recombinant Ad5-based adenovectors that have undergone a complete hexon exchange in an effort to circumvent pre-existing anti-vector humoral immunity. Eighteen different chimeric adenoviral vectors (from subgroups A, B, C, D, and E) have been constructed using a combination of direct cloning and bacterial homologous recombination methods. However, only chimeric Ad5-based constructs in which the hexons from Ad1, Ad2, Ad6, and Ad12 are incorporated in place of the Ad5 hexon were successfully rescued into viruses. Despite several attempts, the remaining fourteen chimeric adenovectors were not rescuable. In vivo rodent studies using transgenes for human immunodeficiency virus type 1 (HIV-1) gag and secreted human alkaline phosphatase (SEAP) suggest that the Ad5/Ad6-gag chimera (wherein Ad5 hexon was replaced with that of Ad6) is able to evade neutralizing antibodies generated against Ad5 vector efficiently. However, it appears that cross-reactive cytotoxic T lymphocytes (CTL) may also play a role in controlling in vivo infectivity of Ad5/Ad6-gag chimera. The Ad5/Ad12 chimera was found to be extremely ineffective in the i.m. delivery and expression of HIV-1 gag in mice compared to the Ad5/Ad6 construct. Implications of these results will be discussed.
Self Recognition in the Ig Superfamily (2000)

The homophilic binding of extracellular domains of membrane-bound immunoglobulin superfamily (IgSF) molecules is often required for intercellular adhesion and signaling. Carcinoembryonic antigen (CEA), a member of the IgSF, is a widely used tumor marker that functions <i>in vitro</i> as a homotypic intercellular adhesion molecule. CEA has also been shown to contribute to tumorigenicity by inhibiting cellular differentiation, an effect that requires the homophilic binding of its extracellular domains. It was of interest, therefore, to identify small subdomain sequences in CEA that could serve as a focus in the design of peptides that disrupt CEA-mediated intercellular adhesion. Three subdomains in the N-terminal domain of CEA, identified by site-directed deletions and point mutations, were shown to be required for intercellular adhesion. Cyclized peptides representing two of these subdomains, <sup>42</sup>NRQII and<sup>80</sup>QNDTG, were found to be effective in blocking CEA-mediated cellular aggregation when added to CEA-expressing transfectants in suspension. Intermolecular binding involving each of these subdomains is therefore essential for intercellular adhesion and cannot be compensated for by known binding contributions of other regions in the CEA molecule. In further support of this assumption, the binding epitope of an anti-CEA monoclonal antibody (monoclonal antibody A20) known to block CEA-mediated adhesion, was shown to bridge two of the three required subdomains: <sup>42</sup>NRQII and<sup>30</sup>GYSWYK.
Chronic dietary anticholinesterase poisoning. (1983)

Five patients presented with chronic gastrointestinal symptoms and nonspecific neurologic complaints, accompanied by reductions in whole blood cholinesterase activity. After the elimination from their diet of fresh fruits and vegetables, the patients became asymptomatic and their blood cholinesterase activity returned to normal levels. The source of this previously unreported type of poisoning is discussed.
Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin. (1990)

One hundred and two benign, mature ovarian teratomas and two immature, malignant teratomas were karyotyped and scored for centromeric heteromorphisms as part of an ongoing project to determine the chromosomal karyotype and the genetic origin of ovarian teratomas and to assess their utility for gene-centromere mapping. Karyotypic analysis of the benign cases revealed 95 46,XX teratomas and 7 chromosomally abnormal teratomas (47,XXX, 47,XX,+8 [two cases], 47,XX,+15, 48,XX,+7,+12 91,XXXX,-13 [mosaic], 47,XX,-15,+21,+mar). Our study reports on the first cases of tetraploidy and structural rearrangement in benign ovarian teratomas. The two immature cases had modal chromosome numbers of 78 and 49. Centromeric heteromorphisms that were heterozygous in the host were homozygous in 65.2% (n = 58) of the benign teratomas and heterozygous in the remaining 34.8% (n = 31). Chromosome 13 heteromorphisms were the most informative, with 72.7% heterozygosity in hosts. The cytogenetic data indicate that 65% of teratomas are derived from a single germ cell after meiosis I and failure of meiosis II (type II) or endoreduplication of a mature ovum (type III); 35% arise by failure of meiosis I (type I) or mitotic division of premeiotic germ cells (type IV).
p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene. (1991)

Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.
Preclinical Development of AS04 (2009)

Recent knowledge on vaccine-induced immunity led to the development of vaccine Adjuvant Systems specially designed and adapted to vaccine needs. AS04 is such a tailored Adjuvant System developed by GlaxoSmithKline Biologicals. This chapter focuses on the methods that were used during the preclinical evaluation of AS04. AS04 consists of the combination of aluminum salts and 3(')-O-deacylated monophosphoryl lipid A (MPL), a detoxified lipid A derivative with retained immunostimulatory capa- city. MPL also induces considerably less pro-inflammatory cytokines, as compared to the parent LPS molecule. Preclinical evaluation of AS04 allowed the determination of the optimal size of MPL particles. The added value of MPL in AS04-based formulations was evidenced by higher vaccine-elicited antibody responses, as well as the induction of higher levels of memory B cells, as compared to aluminum alone formulations. Preclinical evaluation demonstrated the relevance of using AS04 in situations where high and long-lasting antibody levels are needed. This represents the basis for the successful application of AS04 in vaccines against hepatitis B virus and human papillomavirus.
Look who's talking: communication and quorum sensing in the bacterial world (2007)

For many years bacteria were considered primarily as autonomous unicellular organisms with little capacity for collective behaviour. However, we now appreciate that bacterial cells are in fact, highly communicative. The generic term 'quorum sensing' has been adopted to describe the bacterial cell-to-cell communication mechanisms which co-ordinate gene expression usually, but not always, when the population has reached a high cell density. Quorum sensing depends on the synthesis of small molecules (often referred to as pheromones or autoinducers) that diffuse in and out of bacterial cells. As the bacterial population density increases, so does the synthesis of quorum sensing signal molecules, and consequently, their concentration in the external environment rises. Once a critical threshold concentration has been reached, a target sensor kinase or response regulator is activated (or repressed) so facilitating the expression of quorum sensing-dependent genes. Quorum sensing enables a bacterial population to mount a co-operative response that improves access to nutrients or specific environmental niches, promotes collective defence against other competitor prokaryotes or eukaryotic defence mechanisms and facilitates survival through differentiation into morphological forms better able to combat environmental threats. Quorum sensing also crosses the prokaryotic-eukaryotic boundary since quorum sensing-dependent signalling can be exploited or inactivated by both plants and mammals.
Role of Quinones in Toxicology (2000)

Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael acceptors, and cellular damage can occur through alkylation of crucial cellular proteins and/or DNA. Alternatively, quinones are highly redox active molecules which can redox cycle with their semiquinone radicals, leading to formation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can cause severe oxidative stress within cells through the formation of oxidized cellular macromolecules, including lipids, proteins, and DNA. Formation of oxidatively damaged bases such as 8-oxodeoxyguanosine has been associated with aging and carcinogenesis. Furthermore, ROS can activate a number of signaling pathways, including protein kinase C and RAS. This review explores the varied cytotoxic effects of quinones using specific examples, including quinones produced from benzene, polycyclic aromatic hydrocarbons, estrogens, and catecholamines. The evidence strongly suggests that the numerous mechanisms of quinone toxicity (i.e., alkylation vs oxidative stress) can be correlated with the known pathology of the parent compound(s).