gebhart/patrepeval huggingface dataset:
In Vitro Activities of Polymyxin B, Imipenem, and Rifampin against Multidrug-Resistant Acinetobacter baumannii (2006)

In a previous issue of this journal, Yoon et al. reported the activities of polymyxin B, imipenem, and rifampin in double and triple combinations against multidrug-resistant strains of Acinetobacter baumannii (7). These organisms have emerged as important nosocomial pathogens responsible for outbreaks of pneumonia, bacteremia, and sepsis among critically ill patients throughout the world (2, 3). As treatment options are limited, studies demonstrating enhanced activity with combinations of one or more agents are welcomed as they may be useful in selecting and guiding therapy. Yoon et al. have used standard checkerboard microtiter plate and time-kill assays against eight isolates of A. baumannii and conclude that bactericidal synergy can be obtained using polymyxin B in combination with imipenem or rifampin and using all three agents combined. In drawing their conclusions, Yoon et al. have defined synergy in checkerboard assays as a fractional inhibitory concentration index (FICI) of <1.0. We are concerned that this interpretation of the FICI overemphasizes the significance of their findings. It is widely accepted that variability in MIC determinations means the true value may lie within a three-dilution range (6). When testing two antibiotics, this effect is cumulative, and the errors are subsequently incorporated in the FICI score. In view of this, the editorial policies of many journals, including Antimicrobial Agents and Chemotherapy (1) and the Journal of Antimicrobial Chemotherapy (5), require FICI data of <0.5 to be defined as synergy. We feel the inclusion of a third antibiotic is not sufficient reason to merit the use of different criteria for interpreting FICI data. In fact, these scores will carry even greater inbuilt error and should therefore be interpreted at least as conservatively as FICI data derived from testing with two antibiotics. If the results of Yoon et al. are reinterpreted using these criteria, then only three of their double combinations and two of their triple combinations are in fact synergistic, with the remainder having only additive, if any, effect. Some authors have suggested more stringent criteria, with a FICI of ≤0.25 obtained in at least five replicate experiments (6). If these criteria are used, then none of the combinations tested by Yoon et al. are synergistic. Combinations of imipenem, rifampin, and colistin have been found to be effective in animal models (4), and these combinations may yet prove to be the most effective means of treating multidrug-resistant Acinetobacter infections. However, until there is a well-designed clinical trial of the safety and efficacy of these regimens, clinicians should remain cautious in extrapolating the existing in vitro and animal data to humans.
Differential Expression of Telomerase Activity in Hematopoietic Progenitors from Adult Human Bone Marrow (1996)

The loss of telomeric DNA may serve as a mitotic clock which signals cell senescence and exit from cell cycle. Telomerase, and enzyme which synthesizes telomeric repeats de novo, is required to maintain telomere lengths. In humans, significant telomerase activity has been found in cells with essentially unlimited replicative potential such as reproductive cells in ovaries and testes, immortal cell lines and cancer tissues, but not in most normal somatic cells or tissues. We have now examined telomerase expression in subpopulations of hematopoietic cells from adult human bone marrow using a sensitive polymerase chain reaction-based telomeric repeat amplification protocol. Telomerase activity was found at low levels in the highly enriched primitive hematopoietic cells (CD34+CD71loCD45RAlo) and was increased transiently when these cells were cultured in the presence of a mixture of cytokines. In contrast, the early progenitors (CD34+CD71+) expressed telomerase activity at a higher level which was subsequently downregulated in response to cytokines. Telomerase activity remained low in the more mature CD34-cells upon exposure to cytokines. Taken together, our results suggest that telomerase is expressed at a basal level in all hematopoietic cell populations examined, is induced in a primitive subset of hematopoietic progenitor cells and is downregulated upon further proliferation and differentiation of these cells. We have previously observed telomere shortening in cytokine-stimulated primitive hematopoietic cells. The low and transient activation of telomerase activity described here thus appears insufficient to maintain telomere lengths in cultured hematopoietic cells.
Metabolic and genetic characterization of prediabetic states. Sequence of events leading to non-insulin-dependent diabetes mellitus. (1994)

Non-insulin-dependent diabetes mellitus (NIDDM)' is pheno- typically heterogenous and may therefore not be explained by one simple pathophysiological mechanism. Despite the heterog- enous nature of the disease, the major form as discussed in this review is linked to overweight, arterial hypertension, dyslipidemia, and macroangiopathy (coronary heart disease), all condi- tions which become more common with aging (1). This form of NIDDM seems to be growing worldwide in the footsteps of Westernized life style. Around 3% in the Western world suffers from the disease, but in subjects 60 yr and older, the prevalence is as high as 10-20% (2). In certain ethnic populations as the Pima Indians and the Nauruans the prevalence approaches 40% (2). Therefore, NIDDM imposes an enormous burden on the health care system all over the world.
Transcriptional control by nuclear receptors (1991)

Gene regulation by steroid hormones is accomplished by a variety of different mechanisms leading to induction or repression of particular genes. These mechanisms are all mediated by a single class of intracellular hormone receptors, which in the unliganded state are maintained in an inactive form by association with other cellular proteins, including hsp90. Induction of the mouse mammary tumor virus (MMTV) requires binding of the hormone receptor to a hormone-responsive element (HRE) that is precisely organized in a phased nucleosome. After receptor binding, changes in chromatin structure are detected that correlate with binding of transcription factors, including nuclear factor I, to the MMTV promoter. However, although nuclear factor I acts as a basal transcription factor on the MMTV promoter it does not cooperate with the hormone receptors in terms of binding to free DNA, and mutation of the nuclear factor I binding site does not eliminate hormonal stimulation. This residual induction is mediated by octamer motifs upstream of the TATA box that bind the ubiquitous transcription factor OTF-1. Mutation of these octamer motifs does not influence basal transcription in vitro, but completely abolishes the stimulatory effect of progesterone receptor. Glucocorticoids also inhibit expression of many genes. The effect on the gene for the alpha-subunit of chorionic gonadotropin is due to DNA binding competition between the receptor and the protein mediating cAMP induction, whereas repression of the collagenase gene involves an interaction of the receptor with components of the AP1 complex, Jun and Fos.
Molecular Epidemiology of Alzheimer's Disease (1995)

The apolipoprotein E gene is present in the general population in three alleles, ε2, ε3, and ε4, with ε3 being common and ε2 and ε4 relatively less common. Genetic-linkage and association studies have shown that the ε4 allele is overrepresented1 and the ε2 allele is underrepresented2 in patients with Alzheimer's disease. These observations are now generally accepted and have been replicated in numerous clinic-based, case–control studies. In this issue of the Journal, Polvikoski et al.3 describe the results of an investigation of the relation of the apolipoprotein E genotype to the development of Alzheimer's disease in a prospectively studied cohort . . .
Characterization of the 4Mb chalcogenide-random access memory (2006)

The first generation of C-RAM memory is designed to greatly exceed (in density, write speed, endurance) the existing non-volatile memory solutions for space and to close the gap that exists between system requirements and availability. Based on the success of the 64kb C-RAM program, a 4Mb C-RAM prototype has been designed and fabricated in 0.25 mum radiation-hardened CMOS. In this paper we present a description of the 4Mb design as well as results of recent characterization and radiation test of the first pass of prototype parts
Thyroid hormone receptor/and v-erbA. A single amino acid difference in the C-terminal region influences dominant negative activity and receptor dimer formation (1991)

Thyroid hormone receptors are cellular homologues (c-erbAs) of the v-erbA oncoprotein of the avian erythroblastosis virus. Exclusive of the viral gag region, v-erbA differs from the chick c-erbA-alpha receptor by two amino acid changes N-terminal of the DNA binding domain, two amino acid changes in the DNA binding domain, nine amino acid changes in the C-terminal region corresponding to the ligand binding domain of c-erbA, and a nine-amino acid deletion near the C terminus. v-erbA does not bind thyroid hormone and when expressed in cells inhibits the activity of wild-type thyroid hormone receptors. We reported previously that mutants of chick c-erbA/thyroid hormone receptor which lack the DNA binding domain (DBD-) inhibit transcriptional activition by wild-type thyroid hormone and retinoic acid receptors (Forman, B. M., Yang, C.-R., Au, M., Casanova, J., Ghysdael, J., and Samuels, H. H. (1989) Mol. Endocrinol. 3, 1610-1626). This dominant negative activity mapped to a series of hydrophobic heptad motifs which are conserved in the C terminus of these receptors and have been suggested to play a role in receptor dimerization. In this study we show that unlike DBD- c-erbA, DBD- v-erbA does not block receptor activity, suggesting that v-erbA acts by competing for DNA response elements rather than by formation of nonfunctional v-erbA/c-erbA heterodimers. This difference in activity was localized to a single Pro to Ser change in v-erbA just N-terminal of the last heptad motif. Introduction of this Pro to Ser change into DBD- c-erbA resulted in a protein which was inactive both functionally and in blocking receptor dimer formation in vitro.
Mendelian Inheritance in Man: A Catalog of Human Genes and Genetic Disorders (1998)

twelfth edition of this classic reference work includes: * More than 2,000 new entries * A total of more than 9,000 entries * New features and enhancement of the familiar old features * Mapping information on more than 4,000 genes of known function * Information on specific point mutations responsible for more than 700 genetic disorders or neoplasms Mendelian Inheritance in Man (MIM) is a genetic knowledgebase that serves clinical medicine and biomedical research, including the Human Genome Project. It aims to be comprehensive (not only complete, but also collated, integrated, and interpreted), authoritative (not only accurate but also sound in its interpretations and judgements), and timely (not only up-to-date but also historically dimensioned). From a review of the eleventh edition, Reproductive Toxicology: Even the convenience of computer-based forms of MIM cannot eliminate the need for MIM in book form. preface provides a wonderful synopsis of human genetics. information contained in this text serves as a concise review for those with a genetics background. From a review of the tenth edition, New England Journal of Medicine: [Victor McKusick] has been for all these years the shepherd of the development of the field [of clinical genetics]. Perhaps his most important pragmatic achievement has been the 10 editions of Mendelian Inheritance in Man, which rapidly became and has remained the principal source of information on inherited diseases for all clinical geneticists. In addition to the erudite entries in the books, the references given with each description represent a magnificent bibliography of clinical genetics. With McKusick's leadership and continued interest in gene mapping, the book also rep-resents an important compen-dium of the location of genes on specific chromosomes. The book is a magnificent security blanket for the clinical geneticist and should be in the libraries not only of these specialists, but also of all others who see patients with diseases that have genetic components.
Diatom plastids depend on nucleotide import from the cytosol (2009)

Diatoms are ecologically important algae that acquired their plastids by secondary endosymbiosis, resulting in a more complex cell structure and an altered distribution of metabolic pathways when compared with organisms with primary plastids. Diatom plastids are surrounded by 4 membranes; the outermost membrane is continuous with the endoplasmic reticulum. Genome analyses suggest that nucleotide biosynthesis is, in contrast to higher plants, not located in the plastid, but in the cytosol. As a consequence, nucleotides have to be imported into the organelle. However, the mechanism of nucleotide entry into the complex plastid is unknown. We identified a high number of putative nucleotide transporters (NTTs) in the diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum and characterized the first 2 isoforms (NTT1 and NTT2). GFP-based localization studies revealed that both investigated NTTs are targeted to the plastid membranes, and that NTT1 most likely enters the innermost plastid envelope via the stroma. Heterologously expressed NTT1 acts as a proton-dependent adenine nucleotide importer, whereas NTT2 facilitates the counter exchange of (deoxy-)nucleoside triphosphates. Therefore, these transporters functionally resemble NTTs from obligate intracellular bacteria with an impaired nucleotide metabolism rather than ATP/ADP exchanging NTTs from primary plastids. We suggest that diatoms harbor a specifically-adapted nucleotide transport system and that NTTs are the key players in nucleotide supply to the complex plastid.
Heterocyclic synthesis with nitriles: A new approach to Thiophene and Thieno‐[2,3‐d]‐pyrimidine derivatives (1988)

Abstract α‐Cyano‐β‐thiocyanatomethyl cinnamonitrile ( 1 ) was transformed into 5‐acetyl‐2‐amino‐4‐phenylthiophen‐3‐carbonitrile ( 3 ) on refluxing in acetic/sulphuric acid mixture. Compound 3 reacted with trichloroacetonitrile, formamide, carbon disulphide and ethylorthoformate.
Transcranial application of low‐energy laser irradiation improves neurological deficits in rats following acute stroke (2006)

These observations suggest that LLLT applied at different locations in the skull and in a rather delayed-phase post stroke effectively improves neurological function after acute stroke in rats.
Health-related quality of life in patients with pulmonary arterial hypertension (2011)

Background: The aims of the present study were (1) to investigate global and disease specific health-related quality of life (HRQOL) in individuals with Pulmonary Arterial Hypertension (PAH), (2) to examine the correlation between HRQOL and exercise capacity (6-minute walk test, 6MWT) and (3) to compare patientsratings with the age-matched general German population. Methods: 63 consecutive patients (DANA-Point 1) of our pulmonary hypertension program (age 57±17.1 years; 33 male [53%]; 21 [34%] combination therapy; BMI 24.4±4.6) were evaluated by the 6-minute walk test (6MWT), the standardized global SF-36 questionnaire and the specific “Cambridge Pulmonary Hypertension Outcome Review” (CAMPHOR). Results: PAH patients were found to have a reduced HRQOL in physical SF-36 domains. In contrast, the mental health of our PH patients is excellent with SF-36 subscales reaching best possible scores. CAMPHOR “quality of life” score reached the upper tertile, whereas “symptoms” and “activity” scores were in the middle tertile, indicating a reduced physical performance. No significant correlations were found between the 6MWT (401±114 meters) and HRQOL scales. Compared to the age-matched norm population, HRQOL self-ratings were significant reduced in six of eight SF-36 subscales (p≤0.01) except for “pain” (p=0.300) and “mental health” (p=0.093). Conclusion: The study results suggest especially a physical HRQOL limitation for PAH patients. The 6MWT might not be a sufficient surrogate marker for HRQOL domains. HRQOL adds important patient sensitive information beyond the 6MWT and should be considered for clinical study design.
Aberration correction for transcranial photoacoustic tomography of primates employing adjunct image data (2012)

A challenge in photoacoustic tomography (PAT) brain imaging is to compensate for aberrations in the measured photoacoustic data due to their propagation through the skull. By use of information regarding the skull morphology and composition obtained from adjunct x-ray computed tomography image data, we developed a subject-specific imaging model that accounts for such aberrations. A time-reversal-based reconstruction algorithm was employed with this model for image reconstruction. The image reconstruction methodology was evaluated in experimental studies involving phantoms and monkey heads. The results establish that our reconstruction methodology can effectively compensate for skull-induced acoustic aberrations and improve image fidelity in transcranial PAT.
Ion implantation doping and isolation of GaN (1995)

N- and p-type regions have been produced in GaN using Si+ and Mg+/P+ implantation, respectively, and subsequent annealing at ∼1100 °C. Carrier activation percentages of 93% for Si and 62% for Mg were obtained for implant doses of 5×1014 cm−2 of each element. Conversely, highly resistive regions (≳5×109 Ω/⧠) can be produced in initially n- or p- type GaN by N+ implantation and subsequent annealing at ∼750 °C. The activation energy of the deep states controlling the resistivity of these implant-isolated materials is in the range 0.8–0.9 eV. These process modules are applicable to the fabrication of a variety of different GaN-based electronic and photonic devices.
The Preparation and Reactions of 2-Alkyl-1-(or 3)-nitro-2-thiopseudourea. Part I. Reaction with Amines1 (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Preparation and Reactions of 2-Alkyl-1-(or 3)-nitro-2-thiopseudourea. Part I. Reaction with Amines1Lawrence Fishbein and John A. GallaghanCite this: J. Am. Chem. Soc. 1954, 76, 7, 1877–1879Publication Date (Print):April 1, 1954Publication History Published online1 May 2002Published inissue 1 April 1954https://pubs.acs.org/doi/10.1021/ja01636a042https://doi.org/10.1021/ja01636a042research-articleACS PublicationsRequest reuse permissionsArticle Views374Altmetric-Citations40LEARN 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
HE1/NPC2 status in human reproductive tract and ejaculated spermatozoa: consequence of vasectomy (2006)

We have previously demonstrated that the amount of HE1/NPC2 mRNA and protein expressed in the human epididymis is decreased under vasectomy. In this study, western blot analyses showed that many vasovasostomized men are characterized by high HE1/NPC2 levels in spermatozoa when compared with fertile donors. HE1/NPC2 association with sperm from vasovasostomized men was not related to low motility per se as spermatozoa from asthenospermic men have HE1/NPC2 levels similar to those in normal fertile semen samples. Spermatozoa from vasovasostomized men with high amount of HE1/NPC2 are characterized by higher concentration of cholesterol and more lipid raft domains. HE1/NPC2 is secreted in different glycoforms by different tissues of human male reproductive tract. These forms are due to variation in N-glycosylation, and only the deglycosylated form is associated with spermatozoa from some vasovasostomized men. Compared with normal men, seminal plasma of vasectomized men is characterized by a major decrease in immunodetectable HE1/NPC2 without change in the glycosylation pattern. Following surgical vasectomy reversal, seminal plasma HE1/NPC2 was found in similar amounts to the ones characterizing normal men. Considering the potential role of HE1/NPC2 in cholesterol transport during sperm maturation, unusual high levels of this protein associated with spermatozoa of vasovasostomized men may reflect epididymal sequelae occurring when the vas deferens is obstructed.
Streptococcal IgA-binding Proteins Bind in the Cα2-Cα3 Interdomain Region and Inhibit Binding of IgA to Human CD89 (2001)

Certain pathogenic bacteria express surface proteins that bind to the Fc part of human IgA or IgG. These bacterial proteins are important as immunochemical tools and model systems, but their biological function is still unclear. Here, we describe studies of three streptococcal proteins that bind IgA: the Sir22 and Arp4 proteins of Streptococcus pyogenes and the unrelated beta protein of group B streptococcus. Analysis of IgA domain swap and point mutants indicated that two loops at the Calpha2/Calpha3 domain interface are critical for binding of the streptococcal proteins. This region is also used in binding the human IgA receptor CD89, an important mediator of IgA effector function. In agreement with this finding, the three IgA-binding proteins and a 50-residue IgA-binding peptide derived from Sir22 blocked the ability of IgA to bind CD89. Further, the Arp4 protein inhibited the ability of IgA to trigger a neutrophil respiratory burst via CD89. Thus, we have identified residues on IgA-Fc that play a key role in binding of different streptococcal IgA-binding proteins, and we have identified a mechanism by which a bacterial IgA-binding protein may interfere with IgA effector function.
Biochemical, molecular characterization, and glycoproteomic analyses of α1‐proteinase inhibitor products used for replacement therapy* (2006)

Protein chemical characterization of A1PI showed that all A1PI products to some extent differ from A1PI circulating in human plasma. Bioinformatic analysis indicated that removal of C-terminal Lys394 and cysteinylation of Cys232 are unlikely to affect structure and/or function of A1PI but cysteinylation may influence interaction between A1PI and its physiologic ligands. Aralast, Prolastin, and Zemaira contain the same set of N-glycans in the same ratios as those in normal human plasma A1PI. Tri- and tetraantennary structures are responsible for the partitioning into IEF isoforms, with the migration shift of Aralast not being due to any difference in the N-glycosylation, but to the partial loss of the C-terminal lysine.
Laboratory measures of hemostasis and fibrinolysis after intravenous administration of ϵ-aminocaproic acid in clinically normal horses and ponies (2005)

i.v. administration of 30 and 100mg of EACA/kg to clinically normal horses significantly modified some laboratory measures of hemostasis, consistent with its known antifibrinolytic effects. Although enhanced clot maintenance and diminished bleeding were not directly assessed, the clinical use of EACA may benefit some patients.