gebhart/patrepeval huggingface dataset:
Purified cytochrome b561 catalyzes transmembrane electron transfer for dopamine beta-hydroxylase and peptidyl glycine alpha-amidating monooxygenase activities in reconstituted systems. (1987)

Cytochrome b561 from bovine adrenal medulla chromaffin granules has been purified by fast protein liquid chromatography chromatofocusing. The purified cytochrome was reconstituted into ascorbate-loaded phosphatidylcholine vesicles. With this reconstituted system transmembrane electron transfer for extravesicular soluble dopamine beta-hydroxylase activity was demonstrated. In accordance with the model proposed by Njus et al. (Njus, D., Knoth, J., Cook, C., and Kelley, P. M. (1983) J. Biol. Chem. 258, 27-30), catalytic amounts of a redox mediator were necessary to achieve electron transfer between cytochrome and soluble dopamine beta-hydroxylase. Our observations also showed that when membranous dopamine beta-hydroxylase was reconstituted on cytochrome containing vesicles, electron transfer occurred only in the presence of a redox mediator. Since cytochrome b561 has been found in secretory vesicles associated with peptidyl glycine alpha-amidating monooxygenase, electron transfer to this enzyme was also examined. Analogous to the results obtained for dopamine beta-hydroxylase, transmembrane electron transfer to peptidyl glycine alpha-amidating monooxygenase appears to require a redox mediator between cytochrome and this monooxygenase. These observations indicate that purified cytochrome b561 is capable of providing a transmembrane supply of electrons for both monooxygenases. Since no direct protein to protein electron transfer occurs, the results support the hypothesis that the ascorbate/semidehydroascorbate redox pair serves as a mediator for these enzymes in vivo.
Halogen Atoms in the Modern Medicinal Chemistry: Hints for the Drug Design (2010)

A significant number of drugs and drug candidates in clinical development are halogenated structures. For a long time, insertion of halogen atoms on hit or lead compounds was predominantly performed to exploit their steric effects, through the ability of these bulk atoms to occupy the binding site of molecular targets. However, halogens in drug - target complexes influence several processes rather than steric aspects alone. For example, the formation of halogen bonds in ligand-target complexes is now recognized as a kind of intermolecular interaction that favorably contributes to the stability of ligand-target complexes. This paper is aimed at introducing the fascinating versatility of halogen atoms. It starts summarizing the prevalence of halogenated drugs and their structural and pharmacological features. Next, we discuss the identification and prediction of halogen bonds in protein-ligand complexes, and how these bonds should be exploited. Interesting results of halogen insertions during the processes of hit-to-lead or lead-to-drug conversions are also detailed. Polyhalogenated anesthetics and protein kinase inhibitors that bear halogens are analyzed as cases studies. Thereby, this review serves as one guide for the virtual screening of libraries containing halogenated compounds and may be a source of inspiration for the medicinal chemists.
Implementation of maternal blood cell‐free DNA testing in early screening for aneuploidies (2013)

Routine screening for trisomies 21, 18 and 13 by cfDNA testing at 10 weeks is feasible and has a lower FPR than does combined testing, but abnormal results require confirmation by CVS.
Welfare Trends in the Scandinavian Countries. (1994)

Discusses important aspects of the development of the welfare state in the Scandinavian countries and Iceland since the mid-1970s. It focuses on societal changes during a period of modest economic growth. Topics include labour market benefits, education and social mobility, class and inequality, income distribution and trajectories and health.
Nanoring formation by direct-write inorganic electron-beam lithography (2003)

A direct-write inorganic lithography technique is described which is capable of forming nanoscale rings of amorphous metals and semiconductors in glasses. Near-edge electron energy loss spectroscopy and electron diffraction using a subnanometer probe are used to analyze the composition and formation mechanism of these nanorings. The optical absorption cross section of one ring is calculated by multiple scattering methods. Applications in quantum electronics and the design of media with dielectric properties are suggested.
In-vitro Allergiediagnostik (2015)

Zusammenfassung Die allergologische In-vitro-Diagnostik zeigt in den letzten Jahren vielfältige dynamische Entwicklungen und Fortschritte. Dies ist zum einen der Verfügbarkeit von sogenannten molekularen Komponenten der verschiedenen Allergene geschuldet, die heute eine komponentenbasierte Diagnostik erlauben. Diese ist zur Risikoabschätzung und Stratifizierung von Patienten sowie zur Auswahl der geeigneten (spezifischen) Immuntherapie essentiell. Darüber hinaus sind Fortschritte zu verzeichnen in der Differentialdiagnose von Nahrungsmittelunverträglichkeiten und –allergien. Die zelluläre Diagnostik ist ebenfalls auf dem Vormarsch, wie z.B. mit den basophilen Aktivierungstests. Die jüngsten Entwicklungen werden in diesem Artikel diskutiert.
Systematic identification of type I and type II interferon-induced antiviral factors (2012)

Type I and type II interferons (IFNs) are cytokines that establish the cellular antiviral state through the induction of IFN-stimulated genes (ISGs). We sought to understand the basis of the antiviral activity induced by type I and II IFNs in relation to the functions of their ISGs. Based on gene expression studies, we systematically identified antiviral ISGs by performing blinded, functional screens on 288 type I and type II ISGs. We assessed and validated the antiviral activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV), and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34 ISGs that elicited an antiviral effect on the replication of either one or both viruses. Fourteen ISGs have uncharacterized antiviral functions. We further defined ISGs that affect critical life-cycle processes in expression of VSV protein and MHV-68 immediate-early genes. Two previously undescribed antiviral ISGs, TAP1 and BMP2, were further validated. TAP1-deficient fibroblasts were more susceptible to VSV infection but less so to MHV-68 infection. On the other hand, exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These results delineate common and distinct sets of type I and type II IFN-induced genes as well as identify unique ISGs that have either broad or specific antiviral effects on these viruses.
ChemInform Abstract: ONE‐POT PHASE‐TRANSFER‐CATALYZED N‐ALKYLATION OF DIPHENYLPHOSPHINAMIDE WITH ALCOHOLS IN THE PRESENCE OF METHANESULFONYL CHLORIDE (1981)

Abstract Diphenylphosphinamid (I) kann mit Hilfe von Methansulfochlorid mit Alkoholen (II) monoal(kyliert und sauer zu primären Aminen (IV) verseift werden.
BER analysis of a noncoherent demodulation of unbalanced DQPSK DSSS (2005)

A conventional demodulator for an unbalanced QPSK direct sequence spread spectrum (DSSS) signal requires carrier coherence in order to prevent cross-talk between the in-phase and quadrature (I & Q) channels of the despreading process. A noncoherent demodulator which tolerates this cross-talk has been proposed, with applicability to pilot-less burst transmission protocols. The paper focuses on the development and verification of an analytic model for the BER performance of this demodulator, and shows that, although the noise contributions of the cross-talk terms can be high, the resultant impact on BER is only slight.
Vagal stimulation markedly suppresses arrhythmias in conscious rats with chronic heart failure after myocardial infarction (2005)

Our previous study showed that chronic vagal stimulation (VS) prevented the cardiac remodeling and improved the prognosis of chronic heart failure (CHF) rats after large myocardial infraction (MI). Antiarrhythmic effects of VS were assumed to produce such a beneficial outcome. There-rhythmias. fore, we examined the effects of VS on cardiac ar- The ECG transmitter and a radio-controlled stimulator were implanted in the healed MI rat (n=8). The electrical stimulation of the right cervical vagus started at 3-5 months after MI and lasted for 7 days. ECG data were analyzed for counting the premature ventricular or supraventricular contraction (PVC, PSVC) and for the spectral analysis of heart rate variability. All the rats had a variety of ventricular arrhythmias and the number of PVC or PSVC progressively increased to 5-15% of the total beats. VS effectively suppressed the occurrence of PVCs in 1-2 days. The 24-hour counts of average PVC plus PSVS counts were significantly decreased after VS (793&#177;291 vs. 291&#177;289 counts/hr, p&lt;0.05). The power of high-frequency (0.5-2.0 Hz) oscillations of R-R interval was significantly increased by the VS (1.26&#177;0.47 vs. 3.73&#177;0.74, p<0.01, before and 1 day after stop VS). These results showed that VS markedly suppresses arrhythmias in conscious CHF rats. The antiarrhythmogenic properties may partially account for the beneficial effect of VS on survival of CHF rats.
Executive Summary: Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America (2014)

A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.
Secretion of foreign proteins mediated by chicken lysozyme gene regulatory sequences (2002)

Exploitation of the insulating properties of the complete chicken lysozyme gene domain may facilitate the production of transgenic chicken bioreactors with the capacity to deposit valuable proteins in the egg white. Chimeric genes consisting of the chicken lysozyme gene regulatory sequences and sequences encoding foreign proteins could be inserted randomly into the chicken genome and retain appropriate expression levels. The research reported here established that chicken lysozyme gene regulatory sequences can be used to direct the production and secretion of green fluorescent protein (used as a reporter protein) in transiently transfected chicken blastodermal cells. Attempts to verify these findings in transgenic hens are currently in progress. To provide a rapid means of generating constructs encoding other foreign proteins under the control of lysozyme gene regulatory sequences that can facilitate the secretion of heterologous proteins in vivo, a generic lysozyme gene regulatory scaffold was created using a poxvirus-mediated gene targeting system.
H. pylori in the pathogenesis of duodenal ulcer: interaction between duodenal acid load, bile, and H. pylori (2000)

The duodenal acid load may be the critical factor to explain the ability of H. pylori to colonize the duodenal bulb by precipitating glycine-conjugated bile salts. The combination of a high duodenal acid load and H. pylori infection is likely the critical event in the pathogenesis of H. pylori-related duodenal ulcer disease.
Structure and Expression of the Human Motilin Gene (1989)

The human motilin gene was isolated from a human genomic library and its structure was determined by restriction mapping and DNA sequence analysis. The gene consists of five exons separated by four introns spanning approximately 9 kb of genomic DNA. Exon I encodes the 5' untranslated portion of the motilin mRNA. Exons II and III encode the signal peptide and the 22-amino-acid motilin peptide; codons encoding the motilin moiety are split by an intron. The carboxy-terminal motilin-associated peptide (MAP) is largely encoded by Exons III and IV with the last two amino acids of the motilin precursor and the 3' untranslated region encoded by Exon V. Thus, the motilin gene has an unusual structure in which a small bioactive peptide is encoded on two distinct exons. Examination of the expression of the human and nonhuman primate motilin gene by Northern hybridization analysis indicates that it is expressed in a number of gastrointestinal and extragastrointestinal tissues.
Peptide Derivatives Containing Two Trifunctional Amino Acids (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPeptide Derivatives Containing Two Trifunctional Amino AcidsR. F. Fischer and R. R. WhetstoneCite this: J. Am. Chem. Soc. 1954, 76, 20, 5076–5080Publication Date (Print):October 1, 1954Publication History Published online1 May 2002Published inissue 1 October 1954https://pubs.acs.org/doi/10.1021/ja01649a019https://doi.org/10.1021/ja01649a019research-articleACS PublicationsRequest reuse permissionsArticle Views141Altmetric-Citations25LEARN 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
Axonal Regeneration and Lack of Astrocytic Gliosis in EphA4-Deficient Mice (2004)

Spinal cord injury usually results in permanent paralysis because of lack of regrowth of damaged neurons. Here we demonstrate that adult mice lacking EphA4 (-/-), a molecule essential for correct guidance of spinal cord axons during development, exhibit axonal regeneration and functional recovery after spinal cord hemisection. Anterograde and retrograde tracing showed that axons from multiple pathways, including corticospinal and rubrospinal tracts, crossed the lesion site. EphA4-/- mice recovered stride length, the ability to walk on and climb a grid, and the ability to grasp with the affected hindpaw within 1-3 months of injury. EphA4 expression was upregulated on astrocytes at the lesion site in wild-type mice, whereas astrocytic gliosis and the glial scar were greatly reduced in lesioned EphA4-/- spinal cords. EphA4-/- astrocytes failed to respond to the inflammatory cytokines, interferon-gamma or leukemia inhibitory factor, in vitro. Neurons grown on wild-type astrocytes extended shorter neurites than on EphA4-/- astrocytes, but longer neurites when the astrocyte EphA4 was blocked by monomeric EphrinA5-Fc. Thus, EphA4 regulates two important features of spinal cord injury, axonal inhibition, and astrocytic gliosis.
Recombinant vector vaccines in vaccinology. (1994)

The development of recombinant vector vaccines will be guided by nearly two centuries of research in vaccinology and immunology. Experimental vector vaccines may be of viral, bacterial or genetic composition and their acceptability will depend on safety, efficacy, and practicality as seen by the user, the developer, and the licensing authority. Recombinant vector vaccines will need to compete with alternative vaccine approaches and may find special use for non-propagable agents, immunization in early life, fertility control, and emerging infectious agents. Needs of the developing nations that include low cost, temperature stability, and ease of administration may be met, in part at least, by the vector vaccine approach.
Regulation of Immune Responses and Autoimmune Encephalomyelitis by PPARs (2010)

PPARs are members of the steroid hormone nuclear receptor superfamily and play an important role in regulating inflammation as well as lipid metabolism. The PPAR subfamily has been defined as PPARα, PPARβ/δ, and PPARγ, each with different ligands, target genes, and biological roles. PPARs regulate the expression of target inflammatory genes through mechanisms involving both transactivation and transrepression. The anti-inflammatory properties of PPAR agonists have led to the investigation of PPAR functions in regulating autoimmune encephalomyelitis. This paper will summarize some of the general mechanisms by which PPARs regulate inflammatory gene expression and focus on the recent advances of PPAR regulation of autoimmune encephalomyelitis.
Suppression of human alpha-globin gene expression mediated by the recombinant adeno-associated virus 2-based antisense vectors. (1994)

We sought to investigate the usefulness of the adeno-associated virus 2 (AAV)-based vectors to suppress the excess production of the human alpha-globin gene product towards developing a treatment modality for beta-thalassemia since accumulation of free alpha-globin reduces the lifespan of red blood cells in these patients. We constructed recombinant AAV virions containing the human alpha-globin gene sequences in antisense orientation driven by the herpesvirus thymidine kinase (TK) promoter, the SV40 early gene promoter, and the human alpha-globin gene promoter, respectively, as well as a bacterial gene for resistance to neomycin (neoR) as a selectable marker. These recombinant virions were used to infect a human erythroleukemia cell line (K562) that express high levels of alpha-globin mRNA. Clonal populations of neoR cells were obtained after selection with the drug G418, a neomycin analogue. Total genomic DNA samples isolated from these cells were analyzed on Southern blots to document stable integration of the transduced neo and alpha-globin genes. Total cellular RNA samples isolated from mock-infected and recombinant virus-infected cultures were also analyzed by Northern blots. Whereas the TK promoter-driven antisense alpha-globin sequences showed no inhibition of expression of the endogenous alpha-globin gene, the SV40 promoter and the alpha-globin gene promoter-driven antisense alpha-globin sequences suppressed the expression of this constitutively over-expressed gene by approximately 29 and 91%, respectively, at the transcriptional level. These studies suggest the feasibility of utilizing the AAV-based antisense gene transfer approach in the potential treatment of beta-thalassemia.
Polyamide Nucleic Acid−DNA Chimera Lacking the Phosphate Backbone Are Novel Primers for Polymerase Reaction Catalyzed by DNA Polymerases (1998)

A peptide nucleic acid (PNA) oligomer, an analogue of DNA, was examined for its ability to function as a primer or a template to support DNA synthesis catalyzed by DNA polymerases. The analogue, (PNA)19-TpG-OH, comprised of 19 bases in the form of PNA followed by a dinucleotide (TpG-OH) with a single phosphate and a free 3'OH terminus, was recognized as a bona fide primer by 2 reverse transcriptases and also by the Klenow fragment of E. coli DNA polymerase I. The 21-mer PNA chimera is extended on both RNA and DNA templates by all three polymerases. The specificity of binding of the PNA chimeric primer/DNA template at the template-primer binding site of the enzyme was shown by its photo-cross-linking ability to the enzyme which could be effectively competed out by another TP but not by template or primer alone. Furthermore, the chimeric TP-enzyme covalent complex was found to be catalytically active as judged by its ability to incorporate one nucleotide onto the 3'OH terminus of the immobilized primer. PNA sequences were also recognized as template when annealed with a DNA primer. These observations are in variance with the conventional suggestion that the phosphate backbone in the duplex region is essential for recognition and binding by DNA polymerases. The efficient extension of (PNA)19-TpG-OH suggests that the diameter of the duplex region of template primer rather than the phosphate backbone may be sufficient for recognition by DNA polymerases.
A Randomized Trial of Replacement Antioxidant Vitamin Therapy for Neutrophil Locomotory Dysfunction in Blunt Trauma (1991)

Studies in patients with serious trauma indicate that the observed neutrophil (PMN) locomotory dysfunction is partly the result of auto-oxidation as shown by evidence of preactivation, diminished reducing capacity, and low serum and cellular ascorbic acid andα-tocopherol. To investigate whether replacement of the antioxidant vitamins ascorbic acid andα-tocopherol can improve the PMN locomotory defect, ascorbic acid,α-tocopherol, ascorbic acid andα-tocopherol, or placebo was administered to a total of 46 victims of blunt trauma. PMN locomotion was quantitated using a micropore filter assay. Locomotion data were analyzed by repeated measures analysis with a split plot design and data for days 2-6 after injury were compared. Compared with placebo, the antioxidants improved PMN locomotion. The mean differences in distance migrated (treated minus placebo) were ascorbic acid andα-tocopherol = 11.3 ± 3.0μm (one-tailedp= 0.001) (mean ± SE); ascorbic acid = 4.7 ± 3.4μm (p= 0.19); andα-tocopherol = 3.3 ± 2.9μm (p= 0.27). Although both antioxidants given together produced the best results, a plot of the 95% confidence intervals indicates that ascorbic acid andα-tocopherol, either given alone, were also better than placebo. We conclude that antioxidant replacement therapy significantly improves the PMN locomotory abnormality in blunt trauma.
High-resolution full-field optical coherence tomography with a Linnik microscope (2002)

We describe an original microscope for high-resolution optical coherence tomography applications. Our system is based on a Linnik interference microscope with high-numerical-aperture objectives. Lock-in detection of the interference signal is achieved in parallel on a CCD by use of a photoelastic birefringence modulator and full-field stroboscopic illumination with an infrared LED. Transverse cross-section (en-face, or XY) images can be obtained in real time with better than 1-microm axial (Z) resolution and 0.5-microm transverse (XY) resolution. A sensitivity of approximately 80 dB is reached at a 1-image/s acquisition rate, which allows tomography in scattering media such as biological tissues.
Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure (2010)

The defective inter-domain interaction between N-terminal and central domains within RyR2 reduces the binding affinity of CaM to RyR2, thereby causing the spontaneous Ca(2+) release events in failing hearts. Correction of the defective CaM binding may be a new strategy to protect against the aberrant Ca(2+) release in heart failure.
Questão do Software: parâmetros para o desenvolvimento de Software Educativo (1989)

O artigo trata de diversos aspectos envolvidos na producao e distribuicao de software educativo. Inicialmente e feito um resumo dos principais tipos de software educativo. Em seguida e discutido o que se tem feito no Brasil na producao de software educativo. Finalmente sao apresentadas algumas ideias sobre como o software poderia ser produzido, avaliado e distribuido as escolas. Esse processo, certamente, envolveria os orgaos governamentais (em se tratando de escolas publicas) e nesse sentido, o artigo sugere algumas politicas que poderiam ser adotadas.