gebhart/patrepeval huggingface dataset:
Stereochemical studies. LIV. A biogenetic-type asymmetric synthesis of optically active galanthamine from L-tyrosine. (1978)

A biogenetic-type asymmetric synthesis of optically active galanthamine ((+)-4 and (-)-4) is described. Norbelladine derivative (10), having C2 symmetry in the aromatic moiety of C6-C1-N part, was prepared from L-tyrosine, and was converted to narwedinetype enone (11) by oxidation and highly specific asymmetric cyclization. Phosphorylation of phenolic hydroxyl group followed by sodium borohydride reduction afforded 14 having galanthamine skeleton. N-Methylation followed by removal of the methoxycarbonyl and phosphate moieties afforded (+)-galanthamine ((+)-4). Formal total synthesis of (-)-galanthamine ((-)-4) from L-tyrosine via enantiomeric interconversion of narwedine derivative (12) is also described.
Chemiosmotic H<sup>+</sup> cycling across the plasma membrane of the thermoacidophilic archaebacterium <i>Sulfolobus acidocaldarius</i> (1988)

Transitory H + ejection from Sulfolobus acidocaldarius cells induced by oxygen pulses, and anaerobic H + backflow were investigated. Aerobic proton extrusion is inhibited by protonophores, by nigericin and by inhibitors of respiratory electron transport; it is stimulated by DCCD. In contrast, DCCD inhibits the rate of anaerobic H + backflow. Aerobic proton extrusion is significantly enhanced by K + /valinomycin. Apparent H + /O ratios of 2.5–3 are measured. Proton extrusion generates large pH gradients (3–4 units) representing the major contribution to the total proton motive force across the plasma membrane of this thermoacidophilic archaebacterium.
MALDI Imaging of Lipid Biochemistry in Tissues by Mass Spectrometry (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewMALDI Imaging of Lipid Biochemistry in Tissues by Mass SpectrometryKarin A. Zemski Berry†, Joseph A. Hankin†, Robert M. Barkley†, Jeffrey M. Spraggins‡, Richard M. Caprioli‡, and Robert C. Murphy*†View Author Information† Department of Pharmacology, University of Colorado Denver, Mail Stop 8303, 12801 East 17th Avenue, Aurora, Colorado 80045, USA‡ Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, 9160 MRB 3, 465 21st Avenue South, Nashville, Tennessee 37232, USATel.: 303-724-3352. Fax: 303-724-3357. E-mail: [email protected]Cite this: Chem. Rev. 2011, 111, 10, 6491–6512Publication Date (Web):September 26, 2011Publication History Received25 July 2011Published online26 September 2011Published inissue 12 October 2011https://pubs.acs.org/doi/10.1021/cr200280phttps://doi.org/10.1021/cr200280preview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views8303Altmetric-Citations298LEARN 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:Central nervous system,Ions,Lipids,Mass spectrometry,Rodent models Get e-Alerts
Formulation and Compaction of Microspheres (1994)

The factors affecting the tabletability of formulations containing uncoated and/or coated microspheres were discussed by presenting a case study. The size and shape, as well as surface properties of microspherical particles, the type and amount of coating agent, selection of the external additives, and the rate and magnitude of the pressure applied were found to be the most critical factors to be considered in order to obtain and maintain the desired drug release properties of the microspheres. It was found that microcrystalline cellulose was needed in order to produce satisfactory beads in terms of size, shape and surface characteristics. The microsphere formulations, which were found to be highly sensitive to lubrication, were more compressible than their powder forms, but produced much weaker tablets. When coated with Surelease, increasing the amount of coating on the pellets reduced the tensile strength of their compacts. Compaction of the microspheres at high velocities resulted in a decrease in the tensile strength values and an increase in the volumetric strain recovery values. Dissoultion studies revealed that, regardless of the amount of coating applied, the coated microspheres lost their sustained release properties during compaction.
A Multi-Loop Slew-Rate-Enhanced NMOS LDO Handling 1-A-Load-Current Step With Fast Transient for 5G Applications (2020)

Compact low dropout (LDO) with high current handling capability and superior transient response is gaining increasing attention for the battery-powered 5G mobile applications. In this article, a new multiple-loop design technique for fast-transient response LDO regulator design has been proposed and successfully implemented in a 0.13-μm SOI CMOS process for portable smartphone and tablet PC applications. Its supply current capacity is more than 1 A, and its output voltage is from 1.2 to 1.8 V. The proposed LDO features a 10-mV undershoot and overshoot with 1-A/100-ns load current on a 1-μF output capacitor. This superior transient performance is achieved by embodying a novel frequency compensation scheme without penalty of dc loop gain drop in large load current conditions. The dc loop gain is 60 dB and constant regardless of the fact that the load current varies from 0 to 1 A. This contributes to a small load regulation and line regulation of 0.6 μV/A and 0.23 mV/V, respectively. The LDO consumes 35-μA quiescent current in the mission mode and 5 μA in the standby mode. The LDO silicon size is 325 μm × 106 μm.
Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation (2004)

We previously demonstrated that the aspartate protease cathepsin D is activated by ceramide derived from acid sphingomyelinase. Increased expression of cathepsin D in the skin has been reported in wound healing, psoriasis and skin tumors. We explored specific functions of cathepsin D during epidermal differentiation. Protein expression and enzymatic activity of cathepsin D increased in differentiated keratinocytes in both stratified organotypic cultures and in mouse skin during epidermal barrier repair. Treatment of cultured keratinocytes with exogenous cathepsin D increased the activity of transglutaminase 1, known to cross-link the cornified envelope proteins involucrin and loricrin during epidermal differentiation. Inhibition of cathepsin D by pepstatin A suppressed the activity of transglutaminase 1. Cathepsin D-deficient mice revealed reduced transglutaminase 1 activity and reduced protein levels of the cornified envelope proteins involucrin and loricrin. Also, amount and distribution of cornified envelope proteins involucrin, loricrin, filaggrin, and of the keratins K1 and K5 were significantly altered in cathepsin D-deficient mice. Stratum corneum morphology in cathepsin D-deficient mice was impaired, with increased numbers of corneocyte layers and faint staining of the cornified envelope only, which is similar to the human skin disease lamellar ichthyosis. Our findings suggest a functional link between cathepsin D activation, transglutaminase 1 activity and protein expression of cornified envelope proteins during epidermal differentiation.
Long-Lived Mutagenic Radicals Induced in Mammalian Cells by Ionizing Radiation are Mainly Localized to Proteins (2003)

We have provided evidence that long-lived radicals, produced by ionizing radiation, are highly mutagenic and transforming in mammalian cells. Long-lived radicals are scavenged effectively by vitamin C or by epigallocatechin-3-O-gallate (EGCG). Long-lived radicals are not involved in lethality or in the induction of chromosome aberrations. We now report the results of experiments that define the relative amounts of long-lived radicals in DNA and proteins and identify the major protein radicals as sulfinyl radicals (R-CH2-S-O*). To make these assignments, yields of long-lived radicals in gamma-irradiated salmon sperm DNA and albumin were compared by ESR. ESR spectra of long-lived radicals produced in irradiated Syrian hamster embryo (SHE) cells were analyzed precisely and compared with ESR parameters obtained by density functional theory calculations. Long-lived radicals yields of 99.8% were produced in proteins. We also identified a new type of long-lived radical as H-added phenylalanine radicals. While our evidence does not rule out the possibility of important biological consequences of the low-level long-lived radicals created by radiation, it implicates radicals in proteins as playing a key role in genetic effects of ionizing radiation. We suggest that these novel radicals, wherever they reside, need to be considered in explanations of biological sequela of radiation.
Controllable preparation of microscale tubes with multiphase co-laminar flow in a double co-axial microdevice (2009)

This article describes a simple method for the fabrication of microscale polymer tubes. A double co-axial microchannel device was designed and fabricated. Liquid/liquid/liquid multiphase co-laminar flows were realized in a microchannel by choosing working systems. Three kinds of polymeric solutions were selected as the middle phase while a polyethyleneglycol aqueous solution was used as the inner and outer phases in the microfluidic process. The outer and inner phases acted as extractants of the polymer solvent. A stable double core-annular flow was formed by optimizing the composition of the outer and inner phases, and highly uniform tubes were successfully fabricated by the solvent extraction method. Both the outer diameter of the tubes and the wall thickness could be adjusted from 300 microm to 900 microm and from 40 microm to 150 microm by varying the flux of the fluids and the rolling velocity of the collection roller. In addition, titanium dioxide (TiO2) nanoparticles were successfully encapsulated into the polymer tubes with this technique. This technology has the potential to generate hollow fiber membranes for applications in separation and reaction processes.
A Soluble Mannose Receptor Immunoadhesin Enhances Phagocytosis of <i>Pneumocystis carinii</i> by Human Polymorphonuclear Leukocytes <i>In Vitro</i> (2000)

Pneumocystis carinii is an opportunistic pathogen that causes pneumonia in immunocompromised hosts. In the normal host, P. carinii is susceptible to an array of first line host defense mechanisms that are operative in the lung. Alveolar macrophages play a central role in the clearance of inhaled organisms. The macrophage mannose receptor (MR) appears to be sufficient for P. carinii phagocytosis. In individuals infected with the human immunodeficiency virus, MR expression on alveolar macrophages and P. carinii phagocytosis are decreased, however, Fc-receptor mediated phagocytosis remains intact. In this study, we demonstrate that a recombinant soluble MR immunoadhesin, consisting of the essential carbohydrate binding MR ectodomain and the Fc-region of human immunoglobulin (Ig)G1, binds P. carinii and leads to an 8.2-fold increased uptake of P. carinii by phagocytic cells. Our results suggest that the soluble MR immunoadhesin may have therapeutic potential in the treatment of P. carinii infections.
Activation of c-Jun NH2-terminal kinase and subsequent CPP32/Yama during topoisomerase inhibitor beta-lapachone-induced apoptosis through an oxidation-dependent pathway. (1999)

Beta-lapachone (beta-Lap) has been found to inhibit DNA topoisomerases (Topos) by a mechanism distinct from that of other commonly known Topo inhibitors. Here, we demonstrated a pronounced elevation of H2O2 and O2- in human leukemia HL-60 cells treated with beta-Lap. Treatment with other Topo poisons, such as camptothecin (CPT), Vbeta-16, and GL331, did not have the same effect. On the other hand, antioxidant vitamin C (Vit C) treatment effectively antagonized beta-Lap-induced apoptosis. This suggested that a reactive oxygen species (ROS)-related pathway was involved in beta-Lap-induced apoptosis program. We also found that c-Jun NH2-terminal kinase (JNK) but not p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 was persistently activated in apoptosis induced by beta-Lap. Overexpression of a dominant-negative mutant mitogen-activated protein kinase kinase kinase 1 (MEKK1-DN) or treatment with JNK-specific antisense oligonucleotide or Vit C all prevented beta-Lap-induced JNK activation and the subsequent apoptosis. Only the expression of MEKK1-DN, not Vit C treatment, blocked the JNK activity induced by CPT, Vbeta-16, or GL331. These results confirm again that ROS acts as a mediator for JNK activation during beta-Lap-induced apoptosis. Furthermore, we found that beta-Lap can stimulate CPP32/Yama activity, which was, however, markedly inhibited by the MEKK1-DN expression or Vit C treatment. Again, CPT-induced CPP32/Yama activation can be abolished by MEKK1-DN but not by Vit C treatment. Taken together, these results indicate that beta-Lap but not other Topo inhibitors triggers apoptosis signaling, i.e., JNK and subsequent CPP32/Yama activation are mediated by the generation of ROS.
Mechano-electrical feedback in ventricular myocardium (1996)

In the past, cardiac arrhythmias have been most commonly perceived as a result of eEectricaZ disorders of the heart muscle. As this issue of the journal demonstrates, there is mounting evidence that arrhythmias may also be produced by mechanical perturbations or disorders of the myocardium. Clinical data have long suggested that ventricular arrhythmias occur more frequently in patients who suffer from heart failure, dilated cardiomyopathy, ventricular volume or pressure overload, mitral valve prolapse, or dysynergistic ventricular contraction and relaxation [ 1 111. A potential common mechanism underlying all of these observations may be that dilatation or stretch of the myocardial tissue may lead to electrophysiologic changes which produce or facilitate arrhythmias. The phenomenon that electrophysiological changes may result from regional mechanical stretch or global hemodynamic over-load has been termed “contraction-excitation coupling” [12] or “mechano-electrical feedback” 113,141. In the past, however, this phenomenon has not been sufficiently appreciated within the mainstream of cardiovascular research. One reason may be the paucity of direct cellular data on mechano-electrical feedback. It is extremely difficult to maintain a fragile glass-microelectrode stably within a cell of a vigorously beating heart and even harder to ascertain the effects of simultaneously imposed mechanical perturbations. The body surface ECG, on the other hand, is too insensitive and nonspecific to characterize the electrophysiologic changes that result from mechanical strain and promote stretch-activated arrhythmias. Monophasic action potential (MAP) recording, which accurately depicts the time course of transmembrane action potentials while being less sensitive to motion artifacts than intracellular recordings [ 15,161, has been an important tool in evaluating stretch-induced electrophysiological changes in the intact heart. More recently, significant progress has been made toward identifying and characterizing myocardial stretch-activated channels (SACS) by patch clamp technique [17-201. This review summarizes the current state of knowledge on stretch-induced electrophysiological effects and arrhythmias. Some of these concepts have been expressed in a previous publication [21], and newer observations will be presented and discussed in greater detail in the original papers contained in this focus issue of Cardiovascular Research.
<i>In vitro</i> anti‐leukaemia activity of sphingosine kinase inhibitor (2008)

Compelling evidence indicates the role of sphingosine kinase 1 (SPHK1) deregulation in the processes of carcinogenesis and acquisition of drug resistance, providing the rationale for an effective anti-cancer therapy. However, no highly selective inhibitors of SPHK1 are available for in vitro and in vivo studies, except for the newly discovered 'SK inhibitor' (SKI). The present study showed that, in a panel of myeloid leukaemia cell lines, basal level of SPHK1 correlated with the degree of kinase inhibition by SKI. Exposure to SKI caused variable anti-proliferative, cytotoxic effects in all cell lines. In particular, SKI induced an early, significant inhibition of SPHK1 activity, impaired cell cycle progression and triggered apoptosis in K562 cells. Moreover, SKI acted synergistically with imatinib mesylate (IM) to inhibit cell growth and survival. Finally, the inhibitor affected the clonogenic potential and viability of primary cells from chronic myeloid leukaemia (CML) patients, including one harbouring the IM-insensitive Abl kinase domain mutation T315I. Due to the fact that the phenomenon of resistance to IM remains a major issue in the treatment of patients with CML, the identification of alternative targets and new drugs may be of clinical relevance.
Uncovering spatiotemporal biases in place-based social sensing (2020)

Abstract. Places can be characterized by the ways that people interact with them, such as the times of day certain place types are frequented, or how place combinations contribute to urban structure. Intuitively, schools are most visited during work day mornings and afternoons, and are more likely to be near a recreation center than a nightclub. These temporal and spatial signatures are so specific that they can often be used to categorize a particular place solely by its interaction patterns. Today, numerous commercial datasets and services are used to access required information about places, social interaction, news, and so forth. As these datasets contain information about millions of the same places and the related services support tens of millions of users, one would expect that analysis performed on these datasets, e.g., to extract data signatures, would yield the same or similar results. Interestingly, this is not always the case. This has potentially far reaching consequences for researchers that use these datasets. In this work, we examine temporal and spatial signatures to explore the question of how the data acquiring cultures and interfaces employed by data providers such as Google and Foursquare, influence the final results. We approach this topic in terms of biases exhibited during service usage and data collection.
The xeroderma pigmentosum group C gene leads to selective repair of cyclobutane pyrimidine dimers rather than 6-4 photoproducts (2000)

We investigated the contribution of the xeroderma pigmentosum group C (XPC) gene to DNA repair. We stably transfected XPC cells (XP4PA-SV-EB) with XPC cDNA and selected a partially corrected (XP4PA-SE1) and a fully corrected (XP4PA-SE2) clone. Cell survival after UVC (254 nm) exposure was low for XP4PA-SV-EB, intermediate for XP4PA-SE1, and normal for XP4PA-SE2 cells. XP4PA-SV-EB cells had undetectable XPC mRNA and protein levels. XP4PA-SE1 cells had 130% of normal mRNA but 25% of normal protein levels, whereas XP4PA-SE2 cells had an 18-fold mRNA overexpression and normal XPC protein levels compared with normal cells. We measured cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) by using specific mAbs and the ELISA technique. XP4PA-SV-EB cells had no detectable removal of CPD or 6-4PP from their global genome by 24 h after 30 J/m(2) UVC exposure. The partially corrected XP4PA-SE1 cells had normal repair of CPD but minimal repair of 6-4PP by 24 h, whereas the fully corrected XP4PA-SE2 cells regained normal CPD and 6-4PP repair capacities. We also exposed pRSVcat plasmid to UVC (to induce CPD and 6-4PP), to UVC + photolyase (to leave only 6-4PP on the plasmid), or to UVB + acetophenone (to induce only CPD). Host cell reactivation of UVB + acetophenone-, but not of UVC + photolyase-treated plasmids was normal in XP4PA-SE1 cells. Thus, increasing XPC gene expression leads to selective repair of CPD in the global genome. Undetectable XPC protein is associated with no repair of CPD or 6-4PP, detectable but subnormal XPC protein levels reconstitute CPD but not 6-4PP repair, and normal XPC protein levels fully reconstitute both CPD and 6-4PP repair.
<i>BRCA1</i>, a Potential Predictive Biomarker in the Treatment of Breast Cancer (2007)

To date, estrogen receptor, progestogen receptor, and HER2/neu represent molecular biomarkers currently used in routine clinical practice to aid treatment decisions. Over the last few years, a large body of preclinical and retrospective clinical data has accumulated that suggests that BRCA1 mutation functions as a novel predictive marker of response to chemotherapy. This article reviews the role of BRCA1 as a predictive marker of chemotherapy response in breast cancer and examines the link between BRCA1 deficiency and the basal-like phenotype. Search strategy. Data for this article were identified through MEDLINE and PubMed searches for published reports using the terms BRCA1, breast cancer, basal-like, chemotherapy, prognosis, and predictive markers. In some cases, due to the restriction of space, readers are referred to review articles to allow further reading. Only articles published in English were included.
Attenuation of Sindbis virus neurovirulence by using defined mutations in nontranslated regions of the genome RNA (1992)

We examined a panel of Sindbis virus mutants containing defined mutations in the 5' nontranslated region of the genome RNA, in the 3' nontranslated region, or in both for their growth in cultured cells and virulence in newborn mice. In cultured cells, these viruses all had defects in RNA synthesis and displayed a wide range of growth rates. The growth properties of the mutants were often very different in mouse cells from those in chicken cells or in mosquito cells. We hypothesize that host factors, presumably proteins, interact with these nontranslated regions to promote viral replication and that the mammalian protein and the chicken or mosquito protein are sufficiently divergent that alterations in the viral RNA sequence can affect the interactions with these different host proteins in different ways. Some of the mutants were temperature sensitive for plaque formation, whereas one mutant was slightly cold sensitive in its growth in chicken cells. Upon inoculation into mice, viruses that grew well in cultured mouse cells retained their virulence, but mice that succumbed usually had extended survival times. One virulent mutant that grew slightly less well in cultured mouse cells than did the parental virus produced eight times as much virus in mouse brain following intracerebral inoculation, suggesting that changes in these regulatory regions may have tissue-specific as well as host-specific effects. Viruses that were severely crippled in their growth in mouse cells in culture were usually, but not always, attenuated in their virulence. In particular, temperature sensitivity was correlated with attenuation. The effect of two mutations was found to be cumulative, and double mutants that contained mutations in both the 5' and 3' nontranslated regions were more attenuated than was either single mutant. Three of four double mutants tested were severely crippled for virus production in cultured cells and were avirulent for mice, even when inoculated intracerebrally.