gebhart/patrepeval huggingface dataset:
Optical Analog-to-Digital Conversion System Based on Compressive Sampling (2010)

A novel scheme of optical analog-to-digital conversion system is proposed based on compressive sampling and the recent electrical modulated wideband converter. The proposed optical solution is more stable and implementable in practice. Because of the ultranarrow optical pulseswidth, the proposed solution can provide a uniform signal-to-noise attenuate of all frequency bins, compared to its electrical counterpart.
Thermolysis of Free-Radical Initiators:  tert-Butylazocumene and Its 1,3- and 1,4-Bisazo and 1,3,5-Trisazo Analogues (2001)

Four tert-butylazocumenes (4-7) were prepared from the corresponding cyanobenzenes, and their nitrogen evolution kinetics and products were analyzed. In combination with TEMPO, the simplest compound, tert-butylazocumene (4), shows promise as a "one-radical" initiator of styrene polymerization. The ABNO-trapped cumyl radical 29 is a particularly stable trialkylhydroxylamine, whose thermolysis half-life is 2.1 h at 150 degrees C. Taking advantage of this stability, we trapped the cumyl radical centers from 7 to afford tris adduct 32a. While the behavior of the meta bisazoalkane 6 can be mostly predicted from that of 4, the para isomer 5 exhibits both unusual products and kinetics, attributed to the formation of quinodimethane 33 via azo-containing radical 34. In fact, flash vacuum pyrolysis of 5 allowed observation of the (1)H and (13)C NMR spectra of 33, whose persistence even at ambient temperature showed that this quinodimethane is far more stable than the parent 36. Finally, evidence is presented that 7 is an initiator of star polymerization.
Selective inhibition of p38α MAPK improves cardiac function and reduces myocardial apoptosis in rat model of myocardial injury (2006)

p38 MAPK is activated during heart diseases that might associate with myocardial damage and deterioration of cardiac function. In a rat model of myocardial injury, we have investigated cardioprotective effects of the inhibition of p38 MAPK using a novel, orally available p38alpha MAPK inhibitor. Rats were treated with N(omega)-nitro-l-arginine methyl ester (l-NAME, 40 mg.kg(-1).day(-1)) in drinking water plus 1% salt for 14 days and ANG II (0.5 mg.kg(-1).day(-1)) for 3 days. A selective p38alpha MAPK inhibitor, SD-282 (60 mg/kg), was administrated orally, twice a day for 4 days, starting 1 day before ANG II administration. The cardioprotective effects of p38alpha MAPK inhibition were evaluated by improvement of cardiac function, reduction of inflammatory cell infiltration, and cardiomyocyte apoptosis. SD-282 significantly improved cardiac function indicated by increasing stroke volume, cardiac output, ejection fraction, and stroke work and significantly decreasing arterial elastance. SD-282 also significantly reduced macrophage infiltration as judged by reduction of a specific marker, ED-1-positive staining cells (P < 0.05) in the myocardium. Furthermore, cardiomyocyte apoptosis as indicated by caspase-3 immunohistochemical staining was abolished by SD-282, and this effect may contribute to the reduction of myocardial damage evaluated by imaging analysis (P < 0.05 in both cases). Data suggest that p38alpha MAPK may play a critical role in the pathogenesis of cardiac dysfunction. Inhibition of p38alpha MAPK may be used as a novel cardioprotective strategy in attenuation of inflammatory response and deterioration of cardiac function that occurs in acute cardiovascular disease such as myocardial infarction.
Ultrasonic Measurement of Small Displacements and Deformations of Tissue (1982)

A signal processing technique is described for analyzing radio frequency M-mode signals to obtain significantly better depth resolution than previously available. Displacement and deformation waveforms may be measured for displacements less than 0.1 mm and deformations of less than 1 percent. Waveforms of liver dynamics caused by aortic pulsation and vessel diameter variations are presented, and possible tissue characterization applications discussed.
Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Kill Curves versus MIC (2004)

The success of antimicrobial therapy is determined by complex interactions between an administered drug, a host, and an infecting agent. In a clinical situation, the complexity of these interactions is usually reflected by a high variability in the dose-response relationship. Therefore, to minimize the dose-response variability, key characteristics of the drug, the infecting agent and the host have to be taken into account for selecting an appropriate antibiotic and an appropriate dose. Failure to do so may result in either therapeutic failure or emergence of resistant strains.

To date, dose and drug selection is mostly based on a static in vitro parameter, the MIC and on the drug′s serum concentration as a pharmacokinetic parameter. In practice, however, a pharmacodynamic effect in vivo is rather the result of a dynamic exposure of the infective agent to the unbound antibiotic drug fraction at the relevant effect site. Thus, static conditions in an in vitro setting hardly reflect a dynamic situation in a target organ under in vivo conditions. Furthermore, serum concentrations do not reflect the unbound concentrations at the target site.

In recent years substantial efforts were devoted to systematically elucidate the dynamic relationship between pharmacokinetic and pharmacodynamic variables. The main concept of this pharmacokinetic-pharmacodynamic approach is to use the concentration-effect relationship of the drug of interest in dosage adjustment and product development in a logical way and minimize trial-and-error approaches (29, 80). This approach can potentially result in substantial savings of time and expenses and may help to avoid unnecessary and, hence, unethical clinical studies (97). Thus, dosages and dosing intervals of antimicrobial agents should be designed with reference to dynamic pharmacokinetic and pharmacodynamic parameters. Accordingly, several efficacy indices or surrogate markers that take into account both pharmacokinetic and pharmacodynamic information have been defined and used by different authors to describe the antibacterial activity of various classes of antimicrobial agents (100, 106, 59).

Currently there are two main trends for antibiotic pharmacokinetic-pharmacodynamic models; those based on the MIC and those based on a kill-curve approach, both of which will be described in detail in the following.
Meeting of the apical and basolateral endocytic pathways of the Madin-Darby canine kidney cell in late endosomes. (1989)

Electron microscopic approaches have been used to study the endocytic pathways from the apical and basolateral surface domains of the polarized epithelial cell, MDCK strain I, grown on polycarbonate filters. The cells were incubated at 37 degrees C in the presence of two distinguishable markers administered separately to the apical or the basolateral domain. Initially each marker was visualized within distinct apical or basolateral peripheral endosomes. However, after 15 min at 37 degrees C, both markers were observed within common perinuclear structures. The compartment in which meeting first occurred was shown to be a late endosome (prelysosome) that labeled extensively with antibodies against the cation-independent mannose-6-phosphate receptor (MPR) on cryosections. With increasing incubation times, markers passed from these MPR-positive structures into a common set of MPR-negative lysosomes that were mainly located in the apical half of the cell. A detailed quantitative analysis of the endocytic pathways was carried out using stereological techniques in conjunction with horseradish peroxidase and acid phosphatase cytochemistry. This enabled us to estimate the absolute volumes and membrane surface areas of the endocytic organelles involved in apical and basolateral endocytosis.
Hepatitis C virus core protein regulates NANOG expression via the stat3 pathway (2014)

HCV Core plays a role in the development of hepatocellular carcinoma. Aberrant expression of NANOG has been observed in many types of human malignancies. However, relationship between Core and NANOG has not been clarified. In this study, we found that Core is capable of up-regulating NANOG expression. Core-induced NANOG expression was accompanied by enforced expression of phosphorylated stat3 protein and was attenuated by inhibition of stat3 phosphorylation. ChIP showed that phosphorylated stat3 directly binds to the NANOG promoter. Core-induced NANOG expression resulted in enhanced cell growth and cell cycle progression. Knockdown of NANOG blocked the cell cycle at the G0/G1 phases and inhibited the cyclin D1 expression. Our findings provide a new insight into the mechanism of hepatocarcinogenesis by HCV infection.
Gene algD coding for GDPmannose dehydrogenase is transcriptionally activated in mucoid Pseudomonas aeruginosa (1987)

Transcriptional regulation of alginate biosynthesis by Pseudomonas aeruginosa was studied. A DNA region complementing the alg-5 mutation within the alginate gene cluster was found by RNA-DNA dot blot and Northern hybridization to be transcriptionally activated in mucoid P. aeruginosa. This region was subcloned as a 3.2-kilobase BglII-ClaI DNA fragment on the broad-host-range controlled transcription vector pMMB24, and gene products were analyzed by expression from the tac promoter. A 48-kilodalton polypeptide was detected in extracts of P. aeruginosa and 35S-labeled Escherichia coli maxicells. By using the same expression system, GDPmannose dehydrogenase activity was detected in both P. aeruginosa and E. coli. Thus, gene algD coding for this enzyme was found to be present in the transcriptionally active DNA area. Insertion of the xylE gene within the BglII-ClaI fragment disrupted the induction of the 48-kilodalton polypeptide, GDPmannose dehydrogenase activity, and alg-5 complementing ability. With the algD-xylE transcription fusion, activation of algD gene expression was shown to occur in mucoid P. aeruginosa of different origins. In addition, regulation of the algD promoter activity was demonstrated to be mediated by a diffusible factor.
Inducing Embryonic Stem Cells to Differentiate into Pancreatic β Cells by a Novel Three‐Step Approach with Activin A and All‐ Trans Retinoic Acid (2005)

Experimental induction of embryonic stem cells (ESCs) to become pancreatic beta cells can potentially provide ample resource for cell transplantation therapy of type I diabetes mellitus. Most of the previously reported induction strategies were long and complicated, and some required genetic manipulation. Moreover, it has been indicated that the insulin staining of ESC progeny was insulin uptake from the culture medium. Here we show that a simple three-step experimental approach based on the combination induction by activin A, all-trans retinoic acid, and other mature factors is able to induce murine ESCs to differentiate into insulin-producing cells in 2 weeks, and that insulin release of these induced cells is regulated by the glucose concentration. Our insulin-enhanced green fluorescent green protein reporter system excludes the possibility of insulin uptake. Transplantation of these ESC-derived insulin-positive cells can normalize blood glucose levels and rescue the survival of streptozocin-induced diabetic mice. The findings reported here offer a novel in vitro model to study the differentiation mechanism of pancreatic beta cells and a potential source of insulin-producing cells for transplantation therapy of type I diabetes mellitus.
Discovery of Clinical Candidate 1-{[(2 S ,3 S ,4 S )-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design (2017)

Through fragment-based drug design focused on engaging the active site of IRAK4 and leveraging three-dimensional topology in a ligand-efficient manner, a micromolar hit identified from a screen of a Pfizer fragment library was optimized to afford IRAK4 inhibitors with nanomolar potency in cellular assays. The medicinal chemistry effort featured the judicious placement of lipophilicity, informed by co-crystal structures with IRAK4 and optimization of ADME properties to deliver clinical candidate PF-06650833 (compound 40). This compound displays a 5-unit increase in lipophilic efficiency from the fragment hit, excellent kinase selectivity, and pharmacokinetic properties suitable for oral administration.
Biosynthesis of a Head-to-Tail Cyclized Protein with Improved Biological Activity (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTBiosynthesis of a Head-to-Tail Cyclized Protein with Improved Biological ActivityJulio A. Camarero and Tom W. MuirView Author Information The Laboratory of Synthetic Protein Chemistry The Rockefeller University, 1230 York Ave New York 10021, New York Cite this: J. Am. Chem. Soc. 1999, 121, 23, 5597–5598Publication Date (Web):May 29, 1999Publication History Received22 March 1999Published online29 May 1999Published inissue 1 June 1999https://pubs.acs.org/doi/10.1021/ja990929nhttps://doi.org/10.1021/ja990929nrapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1155Altmetric-Citations127LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Biopolymers,Cyclization,Genetics,Ligation,Peptides and proteins Get e-Alerts
The clinical relevance of pharmacological blood pressure lowering mechanisms. (2004)

Hypertension is a major risk factor for stroke, myocardial infarction, heart failure and kidney failure. Clinical trials demonstrate that lowering blood pressure can substantially reduce cardiovascular risk, and current clinical practice guidelines identify lowering blood pressure as a priority in the treatment of people with hypertension and set clear treatment targets. In addition to lifestyle modifications, which should be pursued in all patients, a large number of antihypertensive drugs and combinations of such drugs are part of the modern treatment armamentarium. Following the publication of the Antihypertensive and Lipid-Lowering Treatment to prevent Heart Attack Trial (ALLHAT), some investigators and clinicians have suggested that thiazide diuretics should be the first drug of choice for the treatment of all hypertensive patients. However, antihypertensive drugs differ greatly in their mechanisms of action, pharmacokinetic properties and side effects. There are also large variations among hypertensive patients with regards to the pathophysiology of their blood pressure elevation, response to individual antihypertensive drugs, comorbidities and propensity to drug-related side effects. Therefore, a uniform formula for the treatment of hypertension is not likely to achieve optimal results. Rather, treatment strategies based on careful, comprehensive and individualized patient assessments should be pursued.
Spectral postfilter design based on LSP transformation (2002)

A new spectral postfilter that has high flexibility of design is proposed. In this method, two LSP (line spectrum pair) transformation blocks compute ARMA filter coefficients for the postfilter. The characteristics of the proposed postfilter can be flexibly designed in the frequency domain, because an effect of LSP transformation can be estimated in the frequency domain. As examples of design, an approximation to a conventional LPC-based postfilter, enhancement in selected frequency bands, and a suitable design for a tandem coding are demonstrated.
Roxithromycin Suppresses Mucin Gene Expression in Epithelial Cells (2004)

Macrolide antibiotics are believed to inhibit mucus secretion but the mechanism of action is unclear. This study was designed to investigate an effect of roxithromycin on MUC2 gene expression in cultured intestinal epithelial cells (HM3-MUC2 cells). A reporter gene assay was used for analysis. Roxithromycin suppressed MUC2 gene transcriptional activity in a dose-dependent manner in HM3-MUC2 cells. Phorbol 12-myristate 13-acetate (PMA), lipoteichoic acid (LTA), lipopolysaccharide (LPS) and leukotriene D4 (LTD4) significantly increased MUC2 luciferase activities in the following order: PMA > LTA > LTD4 > LPS. Roxithromycin also decreased MUC2 gene transcriptional activity induced by PMA in a dose-dependent manner. NF-kappaB activation, but not AP-1 activation, was significantly suppressed by roxithromycin in HM3-MUC2 cells. A suppression of NF-kappaB activation was also observed in NCI-H292 cells. These results suggest that roxithromycin suppresses MUC2 gene expression in epithelial cells and that this suppression is probably via inhibition of NF-kappaB activation.
Mutation Surveyor: An In Silico Tool for Sequencing Analysis (2011)

DNA sequencing is widely used for DNA diagnostics and functional studies of genes of interest. With significantly increased sequencing outputs, manual reading of sequence results can impede an efficient and accurate analysis. Mutation Surveyor is a useful in silico tool developed by SoftGenetics that assists the detection of sequence variations within Sanger sequencing traces. This tool can process up to 400 lanes of data at a time with high accuracy and sensitivity. It can effectively detect SNPs and indels in their homozygous or heterozygous states as well as mosaicism. In this chapter, we describe the general application of Mutation Surveyor for DNA sequencing analysis and its unique features.
Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus (1979)

Patients with systemic lupus erythematosus often possess antibodies against two nuclear antigens called Sm and RNP (ribonucleoprotein). We have established the molecular identity of these antigens by analyzing immune precipitates of nuclear extracts from mouse Ehrlich ascites cells labeled with (32)P and (35)S. Anti-Sm serum selectively precipitates six small nuclear RNA molecules (snRNAs); anti-RNP serum reacts with only two of these; and a third serum, characterized as mostly anti-RNP, precipitates a subset of three snRNA bands. Three of the six RNAs are identified by fingerprint analysis as the previously characterized and highly abundant nucleoplasmic snRNA species U1a (171 nucleotides), U1b, and U2 (196 nucleotides). The other three RNAs (U4, U5, and U6) likewise are uridine rich and contain modified nucleotides, but they are smaller, with lengths of about 145, 120, and 95 residues, respectively. Each of the six snRNAs is complexed with and apparently antigenic by virtue of association with specific proteins. All three sera precipitate an identical complement of seven different polypeptides ranging in molecular weight from 12,000 to 35,000; these proteins are abundant in nuclear extracts, but are neither histones nor the major polypeptides comprising the 30S heterogeneous nuclear RNP particles of mammalian nuclei. Our data argue that each of the six snRNAs exists in a separate small nuclear ribonucleoprotein (snRNP) complex with a total molecular weight of about 175,000. We find that human antisera also precipitate snRNAs from a wide range of vertebrate species and from arthropods. We discuss the antigenic snRNPs in relation to the published literature on snRNAs and nuclear RNPs and consider possible functions of snRNPs in nuclear processes.
Immunohistochemical localization of epithelial glycoprotein EGP-2 and carcinoembryonic antigen in normal colonic mucosa and colorectal tumors. (1999)

Epithelial glycoprotein EGP-2 and carcinoembryonic antigen (CEA) are transmembrane glycoproteins and cell surface markers. Eighty-four colorectal tumors including 23 adenomas (2 mild, 13 moderate, and 8 severe atypia) and 61 adenocarcinomas (33 well- and 28 moderately differentiated) as well as adjacent normal colonic mucosa (51 cases) were studied for the immunolocalization of EGP-2 as detected by the monoclonal antibody VU-1D9, and compared with CEA expression. In the normal colonic mucosa, basolateral VU-1D9 expression in the surface epithelial cells was constantly seen in all 51 cases, while weak apical CEA staining in the surface epithelium was seen in 25% (13/51) of the cases. In 91% (21/23) of the adenomas, regardless of the grade of atypia, VU-1D9 labeled the basolateral membrane of a few surface lining cells leaving atypically proliferating glands negative, while CEA expressed strong apical staining in the surface epithelial cells as well as atypically proliferating glands. The well-differentiated adenocarcinomas showed homogeneous basolateral staining for VU-1D9 and strong apical staining for CEA; the moderately differentiated adenocarcinomas showed membranous as well as cytoplasmic VU-1D9 staining and luminal as well as cytoplasmic CEA staining. The VU-1D9 and CEA localizations and the stage of expression in relation to tumor progression were completely different. Strong CEA expression was seen in the adenomatous stage, while the homogeneous VU-1D9 expression required tumor progression to the carcinomatous stage. VU-1D9 especially when applied in combination with CEA, will be a useful marker for colorectal lesions, and its reactivity patterns in carcinoma can predict the prognosis.
The Use of Dried Blood Spot Sampling in the National Social Life, Health, and Aging Project (2009)

The high cooperation rate and quality of the spots collected suggest that the collection of DBSs in population-based research is a feasible and viable alternative to venous blood draws. The relative ease of sample collection, transport, and storage are significant benefits. Care should be taken, however, when comparing results from analysis of DBS samples with those obtained from serum or plasma samples.
Human Coronavirus HKU1 Spike Protein Uses O -Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme (2015)

Human coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic acid moieties on glycoproteins are critical receptor determinants for the hCoV-HKU1 infection. Interestingly, the virus seems to employ a type of sialic acid different from those employed by other group 2a CoVs. In addition, we determined that the HKU1-HE protein is an O-acetylesterase and acts as a receptor-destroying enzyme (RDE) for hCoV-HKU1. This is the first study to demonstrate that hCoV-HKU1 uses certain types of O-acetylated sialic acid residues on glycoproteins to initiate the infection of host cells and that the HKU1-HE protein possesses sialate-O-acetylesterase RDE activity.