gebhart/patrepeval huggingface dataset:
Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents (2013)

Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date.
Herpes Simplex and 'The Herpes Complex': Diverse Observations and A Unifying Hypothesis (1984)

(Delivered at the 99th Ordinary Meeting of the Society for General Microbiology at Reading on 4 January 1984)* THE ELEPHANT, OR THE FORCE OF HABIT A tail behind, a trunk in front, Complete the usual elephant. A tail in front, a trunk behind, Is what you very seldom find. If you for specimens should hunt With trunks behind and tails in front, That hunt would occupy you long; The force of habit is so strong. (A. E. Housman, from A. E. H. by Laurence Housman; Jonathan Cape)
Differential activation of the human trigeminal nuclear complex by noxious and non‐noxious orofacial stimulation (2009)

There is good evidence from animal studies for segregation in the processing of non-nociceptive and nociceptive information within the trigeminal brainstem sensory nuclear complex. However, it remains unknown whether a similar segregation occurs in humans, and a recent tract tracing study suggests that this segregation may not exist. We used functional magnetic resonance imaging (fMRI) to define and compare activity patterns of the trigeminal brainstem nuclear complex during non-noxious and noxious cutaneous and non-noxious and noxious muscle orofacial stimulation in humans. We found that during cutaneous pain, signal intensity increased within the entire rostrocaudal extent of the spinal trigeminal nucleus (SpV), encompassing the ipsilateral oralis (SpVo), interpolaris (SpVi) and caudalis (SpVc) subdivisions. In contrast, muscle pain did not activate SpVi, but instead activated a discrete region of the ipsilateral SpVo and SpVc. Further, muscle noxious stimulation activated a region of the ipsilateral lateral pons in the region of the trigeminal principal sensory nucleus (Vp). Innocuous orofacial stimulation (lip brushing) also evoked a significant increase in signal intensity in the ipsilateral Vp; however, non-noxious muscle stimulation showed no increase in signal in this area. The data reveal that orofacial cutaneous and muscle nociceptive information and innocuous cutaneous stimulation are differentially represented within the trigeminal nuclear complex. It is well established that cutaneous and muscle noxious stimuli evoke different perceptual, behavioural and cardiovascular changes. We speculate that the differential activation evoked by cutaneous and muscle noxious stimuli within the trigeminal sensory complex may contribute to the neural basis for these differences.
Development of an Efficient Process for the Preparation of Sch 39166:  Aziridinium Chemistry on Scale (2004)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDevelopment of an Efficient Process for the Preparation of Sch 39166: Aziridinium Chemistry on ScaleDinesh Gala, Vilas H. Dahanukar, Jeffery M. Eckert, Brian S. Lucas, Doris P. Schumacher, Ilia A. Zavialov, Patrik Buholzer, Peter Kubisch, Ingrid Mergelsberg, and Dominik SchererView Author Information Schering-Plough Research Institute, Department of Synthetic Chemistry, 1011 Morris Avenue, Union, New Jersey 07083, U.S.A. Chemical Development Department, Werthenstein Chemie AG, 6105 Schachen, Switzerland Cite this: Org. Proc. Res. Dev. 2004, 8, 5, 754–768Publication Date (Web):August 3, 2004Publication History Received16 January 2004Published online3 August 2004Published inissue 1 September 2004https://pubs.acs.org/doi/10.1021/op0402026https://doi.org/10.1021/op0402026review-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views1670Altmetric-Citations22LEARN 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 SUBJECTS:Chemical reactions,Impurities,Mixtures,Reagents,Salts Get e-Alerts
Potassium Salts Inhibit Growth of the Cyanobacteria Microcystis spp. in Pond Water and Defined Media: Implications for Control of Microcystin-Producing Aquatic Blooms (1997)

Ten metals were assayed in 21 Indian ponds which comprised three groups: (i) eutrophic alkaline ponds containing <2.5 mM potassium and thick growths of Microcystis aeruginosa or Microcystis flos-aquae during most of the year, (ii) equally eutrophic alkaline ponds containing >2.8 mM potassium and no detectable Microcystis growth, and (iii) oligo- or mesotrophic ponds with various potassium and hydrogen ion concentrations and no persistent Microcystis blooms. The effects of potassium on Microcystis growth were examined in filter-sterilized pond water and in defined culture media. A 50% reduction in the 10-day yield of cultured M. aeruginosa was observed in DP medium and pond water supplemented with 1 and 3 mM KCl, respectively. In contrast, the addition of 2 to 30 mM NaCl did not suppress the growth of M. aeruginosa in either DP medium or pond water. Both 5 mM KCl and 20 mM KHCO(inf3) in J medium strongly inhibited the growth of M. flos-aquae C3-9, whereas 5 to 30 mM NaCl had no effect and 20 mM NaHCO(inf3) was stimulatory. For pond water cultured with a mixture of M. aeruginosa and the duckweed Wolffia arrhiza, M. aeruginosa dominated in unsupplemented water and W. arrhiza dominated in water supplemented with 4.8 mM KCl. Implications for the ecology and control of Microcystis blooms are discussed.
TDP1 and PARP1 Deficiency Are Cytotoxic to Rhabdomyosarcoma Cells (2013)

Selective targeting of TDP1 and/or PARP-1 in rhabdomyosarcoma induces cytotoxicity and sensitizes to DNA damaging agents.
Facial Skeletal Augmentation Using Hydroxyapatite Cement (1993)

This study investigates the use of a new calcium phosphate cement, which sets to solid, microporous hydroxyapatite, for facial bone augmentation. In six dogs, the supraorbital ridges were augmented bilaterally with this hydroxyapatite cement. On one side, the hydroxyapatite cement was placed directly onto the bone within a subperiosteal pocket. On the opposite side, the cement was contained within a collagen membrane tubule and then inserted into a subperiosteal pocket. The use of collagen tubules facilitated easy, precise placement of the cement. All implants maintained their original augmented height throughout the duration of the study. They were well tolerated without extrusion or migration, and there was no significant sustained inflammatory response. Histologic studies, performed at 3, 6, and 9 months revealed that when the cement was placed directly onto bone, progressive replacement of the implant by bone (osseointegration of the hydroxyapatite with the underlying bone) without a loss of volume was observed. In contrast, when the cement-collagen tubule combination was inserted, primarily a fibrous union was noted. Despite such fibrous union, the hydroxyapatite-collagen implant solidly bonded to the underlying bone, and no implant resorption was observed. Hydroxyapatite cement can be used successfully for the experimental augmentation of the craniofacial skeleton and may be applicable for such uses in humans.
An intermolecular base triple as the basis of ligand specificity and affinity in the guanine- and adenine-sensing riboswitch RNAs (2005)

Riboswitches are highly structured RNA elements that control the expression of many bacterial genes by binding directly to small metabolite molecules with high specificity and affinity. In Bacillus subtilis, two classes of riboswitches have been described that discriminate between guanine and adenine despite an extremely high degree of homology both in their primary and secondary structure. We have identified intermolecular base triples between both purine ligands and their respective riboswitch RNAs by NMR spectroscopy. Here, specificity is mediated by the formation of a Watson-Crick base pair between the guanine ligand and a C residue or the adenine ligand and a U residue of the cognate riboswitch RNA, respectively. In addition, a second base-pairing interaction common to both riboswitch purine complexes involves a uridine residue of the RNA and the N3/N9 edge of the purine ligands. This base pairing is mediated by a previously undescribed hydrogen-bonding scheme that contributes to the affinity of the RNA-ligand interaction. The observed intermolecular hydrogen bonds between the purine ligands and the RNA rationalize the previously observed change in specificity upon a C to U mutation in the core of the purine riboswitch RNAs and the differences in the binding affinities for a number of purine analogs.
Nitrite Reductase Gene Enrichment Improves Assimilation of NO2 in Arabidopsis (2001)

Transgenic plants of Arabidopsis bearing the spinach (Spinacia oleracea) nitrite reductase (NiR, EC 1.7.7.1) gene that catalyzes the six-electron reduction of nitrite to ammonium in the second step of the nitrate assimilation pathway were produced by use of the cauliflower mosaic virus 35S promoter and nopaline synthase terminator. Integration of the gene was confirmed by a genomic polymerase chain reaction (PCR) and Southern-blot analysis; its expression by a reverse transcriptase-PCR and two-dimensional polyacrylamide gel electrophoresis western-blot analysis; total (spinach + Arabidopsis) NiR mRNA content by a competitive reverse transcriptase-PCR; localization of NiR activity (NiRA) in the chloroplast by fractionation analysis; and NO(2) assimilation by analysis of the reduced nitrogen derived from NO(2) (NO(2)-RN). Twelve independent transgenic plant lines were characterized in depth. Three positive correlations were found for NiR gene expression; between the total NiR mRNA and total NiR protein contents (r = 0.74), between the total NiR protein and NiRA (r = 0.71), and between NiRA and NO(2)-RN (r = 0.65). Of these twelve lines, four had significantly higher NiRA than the wild-type control (P < 0.01), and three had significantly higher NO(2)-RN (P < 0.01). Each of the latter three had one to two copies of spinach NiR cDNA per haploid genome. The NiR flux control coefficient for NO(2) assimilation was estimated to be about 0.4. A similar value was obtained for an NiR antisense tobacco (Nicotiana tabacum cv Xanthi XHFD8). The flux control coefficients of nitrate reductase and glutamine synthetase were much smaller than this value. Together, these findings indicate that NiR is a controlling enzyme in NO(2) assimilation by plants.
A Randomized, Prospective, Double‐Blind Study on the Efficacy of Dead Sea Salt Nasal Irrigations (2006)

We present a short-term study providing level I evidence on the superiority of DSS over saline nasal irrigation for treatment of chronic rhinosinusitis.
Pentylenetetrazol (Metrazol) in Mental Deficiency (1957)

<h3>Introduction</h3> Pentylenetetrazol (Metrazol) has been used as a respiratory stimulant for 30 years and as a convulsant for 20 years. The pharmacology and chemistry of the drug was described in 1937 by Giessen,<sup>1</sup>who gave a bibliography of the German literature up to that time. The use of pentylenetetrazol as a convulsant is well documented in the American literature. During the past five years, articles<sup>224</sup>have appeared on its use in senile and arteriosclerotic patients, with somewhat contradictory results; the majority felt that it in some way stimulated the patients, reducing the confusion, and caused a general feeling of well being. The beneficial effects have been attributed to the increased metabolism in the brain. Giessen pointed out that pentylenetetrazol increases the cerebral circulation and the amount of oxygen taken up. On the basis of this supposition, it was decided to try pentylenetetrazol on different groups of retarded children
Synthesis of Glycolipid Clusters with Pentaerythritol Cores and Different Ethyleneoxy-Spaced Mannose Residues as Terminal Carbohydrates (2002)

We describe the synthesis of polyantennary glycolipid clusters with pentaerythritol cores. A known protecting group strategy permits the introduction of different hydrophobic moieties and the selective coupling with ethyleneoxy spacers of different lengths. After glycosidation, substances with one, two or three mannose residues as terminal carbohydrate headgroups were isolated. These polyantennary mannosides can be used as attractive tools for targeting of liposomes towards the macrophage mannose receptor.
Mechanisms of Inhibition of Tumor Angiogenesis and Vascular Tumor Growth by Epigallocatechin-3-Gallate (2004)

These data suggest that the green tea gallate or its derivatives may find use in the prevention and treatment of vascular tumors in a chemoprevention or adjuvant setting.
Role of microRNAs in central nervous system development and pathology (2011)

Gene expression regulation is essential for correct functioning of the cell. Complex processes such as development, apoptosis, cell differentiation, and cell cycling require a fine tuning of gene expression. MicroRNAs (miRNAs) are small RNAs that have been recognized as key components of the gene expression regulatory machinery. By sequence complementarity, miRNAs recognize target mRNAs and inhibit their function through degradation or by repressing their translation. The development of the central nervous system (CNS) requires precise and exquisitely regulated gene expression patterns. It is now widely recognized that miRNAs have the capacity to provide such fine regulation both in time and in space. High-throughput analyses as well as classical molecular biology approaches have allowed the identification of essential miRNAs for CNS development and function. Moreover, recent studies in several model organisms are beginning to show intricate regulatory networks involving miRNAs, transcription factors, and epigenetic regulators during CNS development. Here we review recent findings on the role that miRNAs play in the development of the CNS as well as in neuropathologies such as schizophrenia, Parkinson disease, and Alzheimer's disease, among others.
Localization of receptors for luteinizing hormone-releasing hormone in pancreatic and mammary cancer cells. (1991)

Previous work showed that hamster and human pancreatic tumors but not normal pancreata exhibit low-affinity cell-membrane receptors for luteinizing hormone-releasing hormone (LHRH). Although the regression of experimental pancreatic cancers induced by treatment with LHRH agonists or antagonists could be explained in part by the creation of sex-steroid deficiency, direct effects mediated by LHRH receptors might also play a role. Here, we demonstrate that pancreatic tumor cells do exhibit high-affinity binding sites for LHRH, but only in their nuclei; low-affinity sites are associated with the cell membranes. These binding sites appear to be LHRH receptors since electron microscopic immunohistochemical studies show that an antibody to the LHRH receptor reacted with sites in the nucleus of pancreatic tumor cells. Immunoreactive sites in the nucleus also were found in a restricted set of normal hamster pituitary cells thought to be luteinizing hormone-secreting cells and in MXT mouse mammary tumor cells. Such nuclear receptors may be involved in the transmission of the direct action of LHRH analogues on the tumor cells, resulting in the enhancement of programmed cell death.
Using Sentiment Surveys to Predict GDP Growth and Stock Returns (2009)

This study sheds new light on the question of whether or not sentiment surveys, and the expectations derived from them, are relevant to forecasting economic growth and stock returns, and whether they contain information that is orthogonal to macroeconomic and financial data.I examine 16 sentiment surveys of distinct respondent universes and employ the technique of principal components analysis to extract the common signals from the surveys.I show that the ability of different population groups to anticipate correctly economic growth and excess stock returns is not identical, implying that not all sentiment is the same, although there exist some common components.I demonstrate that sentiment surveys have significant predictive power for both GDP growth and excess stock returns, and that the results are robust to the inclusion of information pertaining to the macroeconomic environment and momentum.Furthermore, the findings reject the conventional wisdom that the effect of sentiment is apparent exclusively in small-capitalization stocks.
Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction (2003)

In a population of stable asthmatics short acting beta-agonists, mast cell stabilisers, or anticholinergics will provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects. On average, SABAs resulted in more effective attenuation than mast cell stabilisers, while mast cell stabilisers were more effective than anti-cholinergic agents. Combining SABA and mast cell stabilisers may be appropriate in selected cases. The variability in the individual degree of response to these drugs in multi arm trials suggests clinicians and patients work together to identify the most effective prophylactic therapy.
The processing of hexagonally sampled two-dimensional signals (1979)

Two-dimensional signals are normally processed as rectangularly sampled arrays; i.e., they are periodically sampled in each of two orthogonal independent variables. Another form of periodic sampling, hexagonal sampling, offers substantial savings in machine storage and arithmetic computations for many signal processing operations. In this paper, methods for the processing of two-dimensional signals which have been sampled as two-dimensional hexagonal arrays are presented. Included are methods for signal representation, linear system implementation, frequency response calculation, DFT calculation, filter design, and filter implementation. These algorithms bear strong resemblances to the corresponding results for rectangular arrays; however, there are also many important differences. Some comparisons between the two methods for representing planar data will also be presented.
Palladium-Catalyzed Oxidative Rearrangement of Tertiary Allylic Alcohols to Enones with Oxygen in Aqueous Solvent (2014)

A one-pot procedure for Pd(TFA)2-catalyzed 1,3-isomerization of tertiary allylic alcohols to secondary allylic alcohols followed by a Pd(TFA)2/neocuproine-catalyzed oxidative reaction to β-disubstituted-α,β-unsaturated kenones was developed.
BORON IN PLANT STRUCTURE AND FUNCTION (1998)

New and exciting developments in boron research in the past few years greatly contributed to better understanding of the role of boron in plants. Purification and identification of the first boron-polyol transport molecules resolved much of the controversy about boron phloem mobility. Isolation and characterization of the boron-polysaccharide complex from cell walls provided the first direct evidence for boron crosslinking of pectin polymers. Inhibition and recovery of proton release upon boron withdrawal and restitution in plant culture medium demonstrated boron involvement in membrane processes. Rapid boron-induced changes in membrane function could be attributed to boron-complexing membrane constituents. Boron may affect metabolic pathways by binding apoplastic proteins to cis-hydroxyl groups of cell walls and membranes, and by interfering with manganese-dependent enzymatic reactions. In addition, boron has been implicated in counteracting toxic effects of aluminum on root growth of dicotyledonous plants. Molecular investigations of boron nutrition have been initiated by the discovery of a novel mutant of Arabidopsis thaliana with an altered requirement for boron.
Effects of elevated CO<sub>2</sub> applied to potato roots on the anatomy and ultrastructure of leaves (2011)

The root system of potato (Solanum tuberosum L. cv. Favorita) plants was treated with different O2 and CO2 concentrations for 35 d in aeroponic culture. Under 21 or 5 % O2 in the root zones, the thickness of leaves and palisade parenchyma significantly increased at 3 600 μmol(CO2) mol-1 in the root zone, compared with CO2 concentration 380 μmol mol-1 or low CO2 concentration (100 μmol mol-1). In addition, smaller cells of palisade tissue, more intercellular air spaces and partially two layers of palisade cells were observed in the leaves with root-zone CO2 enrichment. Furthermore, there was a significant increase in the size of chloroplasts and starch grains, and the number of starch grains per chloroplast due to elevated CO2 only under 21 % O2. In addition, a significant decline in the thickness of grana and the number of lamellas, but no significant differences in the number of grana per chloroplast were observed under elevated CO2 concentration. The accumulation of starch grains in the chloroplast under elevated CO2 concentration could change the arrangement of grana thylakoids and consequently inhibited the absorption of sun radiation and photosynthesis of potato plants.