gebhart/patrepeval huggingface dataset:
Transcriptional slippage occurs during elongation at runs of adenine or thymine inEscherichia coli (1990)

A run of 11 adenine or thymine residues at the 5' end of an out-of-frame lacZ gene causes a high level of beta-galactosidase expression in E. coli. This effect was not observed for a run of guanine residues. Reverse transcription of mRNA isolated from E. coli containing the run of 11 A's reveals heterogeneity of transcript length while reverse transcription of mRNA isolated from S. cerevisiae containing the same gene shows no heterogeneity. Protein sequencing of the beta-galactosidase molecules derived from the out-of-frame construct containing a run of adenines reveals the addition of a lysine at the run. A new method was developed where messages small enough to allow resolution of single nucleotide differences on an acrylamide gel are electrophoresed, electroblotted onto nylon and probed. This confirmed the reverse transcription results and showed that additional residues can be added to transcripts derived from DNA containing 10 or 11 thymine residues. A mechanism for slippage is discussed where the A-U rich RNA-DNA hybrid can denature during elongation and rehybridize in an offset position, causing the addition of extra residues to the transcript.
Can we predict mitral valve repair rates by individual surgeons' mitral volume? (2011)

Mitral valve repair is desirable and superior to replacement in nearly all instances of mitral disease. The excellent long-term results have facilitated changing the indications for mitral surgery.1 Mitral patients can potentially be referred earlier, in a lower functional class or even when asymptomatic, before left ventricular (LV) dysfunction and dilation occur. This synopsis considers clinical and individual surgeon factors that predict mitral repair, which could lead to higher repair rates and improved outcomes.2
Patterns of antisocial behaviour from early to late adolescence (2005)

As not all antisocial behaviour is recorded by police, it is valuable to measure adolescents' own reports of their involvement in such behaviour. Self-reported measures allow questions to be answered about the types, rates and across-time patterns of adolescent antisocial behaviour and the degree to which such behaviour results in criminal justice contact. Diana Smart, Suzanne Vassallo, Ann Sanson and Inez Dussuyer analyse data from a large longitudinal study of Victorian children.
Assemblin Homolog of Herpes Simplex Virus Type 1 Retains Proteolytic Activity When Expressed as a Recombinant Two-Chain Enzyme (1997)

The herpes simplex virus type 1 (HSV) maturational proteinase is synthesized as a precursor that undergoes two autoproteolytic cleavages; one at its (M)aturational site, which eliminates its carboxyl "tail," and a second at its (R)elease site, which separates the amino proteolytic half of the precursor from its nonproteolytic carboxyl half. In cytomegalovirus (CMV) the proteolytic half of the precursor, called assemblin, undergoes a third cleavage at an (I)nternal site that converts it from a single-chain to a two-chain enzyme that retains activity. The HSV assemblin homolog has no I site and therefore does not form a counterpart two-chain enzyme. In the work reported here we have cloned and expressed HSV sequences that encode mimics of the An and Ac subunits of two-chain CMV assemblin. We show that when these HSV sequences are coexpressed in eukaryotic cells, the resulting subunits associate spontaneously to form an active two-chain enzyme. We also show that the two-chain HSV enzyme, like the natural one-chain form, retains its marked preference for HSV over CMV substrates, and that intertypic recombinant two-chain assemblin (e.g., HSV An/CMV Ac) does not form because the cross-species subunits do not interact. We conclude from these results that (i) there are not intrinsic structural differences in the HSV assemblin homolog that preclude its functioning as a CMV-like two-chain enzyme, (ii) the substrate selectivity shown by the single-chain HSV enzyme was not noticeably relaxed in the HSV two-chain mimic, and (iii) the interactive domains, through which the An and Ac portions of the single-chain enzymes associate, differ between HSV and CMV.
Human group-specific component (Gc) is a member of the albumin family. (1985)

The group-specific component (Gc) is the major vitamin D-binding protein in plasma. The gene encoding Gc is linked, on human chromosome 4, to the albumin and alpha-fetoprotein genes. These two genes previously were shown to have evolved from a smaller ancestral gene by intragenic triplication. Recombinant plasmids containing human cDNA encoding Gc have been isolated by screening an adult human liver library with a mixed oligonucleotide probe. Characterization of Gc cDNA has provided the complete amino acid sequence of the protein and revealed strong sequence homology with albumin and alpha-fetoprotein. Of particular interest is a conserved pattern of disulfide bridges that form the triple-domain structures in albumin, alpha-fetoprotein, and Gc. Gc cDNA was used as a probe in Southern blot analysis of somatic-cell hybrids to confirm that the Gc locus is on chromosome 4.
Spermidine uptake by type II pulmonary epithelial cells in primary culture (1989)

The transport pathway for the polyamine spermidine (SPD) was characterized in primary isolates of type II pulmonary epithelial cells from rat lungs. [14C]spermidine was accumulated by type II cells via a temperature-, sodium-, and concentration-dependent saturable pathway, with an apparent Km of 0.48 microM and a maximum velocity (V max) of 0.32 pmol.microgram DNA-1.min-1. SPD uptake was inhibited by gramicidin and by reduced extracellular sodium but was unaffected by alpha-aminoisobutyric acid (AIB), which entered the cells by a similar saturable pathway. Uptake of SPD also was inhibited by the exogenous polyamines putrescine (PUTR) and spermine (SPM), as well as by the methylglyoxal bis(guanylhydrazone) (MGBG) and by paraquat (PQ). The order of potency of these inhibitors was SPM greater than PUTR = MGBG much greater than PQ. The absence of serum reduced the Vmax of the system slightly but had no effect on the apparent Km. In contrast, after 3 days in primary cell culture, the kinetics of SPD transport were altered by decreases in both the Km and Vmax of the uptake process. These observations indicate that type II pulmonary epithelial cells exhibit a pathway of polyamine uptake with general characteristics similar to those observed previously in intact lung tissue and other cell types.
Stress Signals Utilize Multiple Pathways To Stabilize p53 (2000)

The p53 tumor suppressor is activated by many diverse stress signals through mechanisms that result in stabilization and accumulation of the p53 protein. p53 is normally degraded through the proteasome following interaction with MDM2, which both functions as a ubiquitin ligase for p53 and shuttles to the cytoplasm, where p53 degradation occurs. Stabilization of p53 in response to stress is associated with inhibition of MDM2-mediated degradation, which has been associated with phosphorylation of p53 in response to DNA damage or activation of ARF. In this study we show distinct responses, as measured by phosphorylation, transcriptional activity, and subcellular localization, of p53 stabilized by different activating signals. Although normal cells and wild-type p53-expressing tumor cells showed similar responses to actinomycin D and camptothecin treatment, the transcriptional activity of stabilized p53 induced by deferoxamine mesylate, which mimics hypoxia, in normal cells was lost in all three tumor cell lines tested. Our results show that multiple pathways exist to stabilize p53 in response to different forms of stress, and they may involve down-regulation of MDM2 expression or regulation of the subcellular localization of p53 or MDM2. Loss of any one of these pathways may predispose cells to malignant transformation, although reactivation of p53 might be achieved through alternative pathways that remain functional in these tumor cells.
A Direct Catalytic Enantioselective Aldol Reaction via a Novel Catalyst Design (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Direct Catalytic Enantioselective Aldol Reaction via a Novel Catalyst DesignBarry M. Trost and Hisanaka ItoView Author Information Department of Chemistry Stanford University Stanford, California 94305-5080 Cite this: J. Am. Chem. Soc. 2000, 122, 48, 12003–12004Publication Date (Web):November 17, 2000Publication History Received15 August 2000Published online17 November 2000Published inissue 1 December 2000https://doi.org/10.1021/ja003033nCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views7968Altmetric-Citations430LEARN 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 InReddit Read OnlinePDF (39 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aldehydes,Aldol reactions,Catalysts,Chemical structure,Zinc Get e-Alerts
Akt Phosphorylation of Serine 21 on Pak1 Modulates Nck Binding and Cell Migration (2003)

The p21-activated protein kinases (Paks) regulate cellular proliferation, differentiation, transformation, and survival through multiple downstream signals. Paks are activated directly by the small GTPases Rac and Cdc42 and several protein kinases including Akt and PDK-1. We found that Akt phosphorylated and modestly activated Pak1 in vitro. The major site phosphorylated by Akt on Pak1 mapped to serine 21, a site originally shown to be weakly autophosphorylated on Pak1 when Cdc42 or Rac activates it. A peptide derived from the region surrounding serine 21 was a substrate for Akt but not Pak1 in vitro, and Akt stimulated serine 21 phosphorylation on the full-length Pak1 much better than Rac did. The adaptor protein Nck binds Pak near serine 21, and its association is regulated by phosphorylation of this site. We found that either treatment of Pak1 in vitro with Akt or coexpression of constitutively active Akt with Pak1 reduced Nck binding to Pak1. In HeLa cells, green fluorescent protein-tagged Pak1 was concentrated at focal adhesions and was released when Akt was cotransfected. A peptide containing the Nck binding site of Pak1 fused to a portion of human immunodeficiency virus Tat to allow it to enter cells was used to test the functional importance of Nck/Pak binding in Akt-stimulated cell migration. This Tat-Nck peptide reduced Akt-stimulated cell migration. Together, these data suggest that Akt modulates the association of Pak with Nck to regulate cell migration.
Efficacy of foot orthoses. What does the literature tell us? (2000)

This paper reviews the literature relating to foot orthoses, in particular foot orthoses that attempt to alter biomechanical function. Whilst few well-controlled studies have been performed, the findings from the available literature are generally positive. The authors provide an overview of this literature and then summarise the findings. The literature is categorised into six research outcome areas: (i) patient satisfaction, (ii) pain and deformity, (iii) plantar pressures, (iv) position and motion, (v) muscle activity, and (vi) oxygen consumption. In addition, the difficulties associated with researching foot orthoses are discussed.
<title>Nonlinear motion-compensated interpolation for low-bit-rate video</title> (2000)

By augmenting the ITU-T H.263 standard bit stream with supplementary motion vectors for to-be-interpolated frames, a new deformable block-based fast motion-compensated frame interpolation (DB-FMCI) scheme is presented. Unlike other motion-compensated interpolation methods, which assume a constant motion velocity between two reference P frames, the proposed scheme takes into account the non-linearity of motion to achieve a better interpolation result. The supplementary motion information for the so-called M frame (motion frame) is defined, which consists of compressed residues of linear and non-linear motion vectors. The non-linear motion vectors of skipped frames are used at the decoder to determine the 6- parameter affine-based DB-FMCI. Experimental results show that the proposed non-linear enhancement scheme can achieve a higher PSNR value and better visual quality in comparison with traditional methods based only on the linear motion assumption.
Atrioventricular Time Sequence and Myocardial Efficiency (1973)

AbstractThe importance of atrial contribution to ventricular performance has been thoroughly studied (Burchell, 1964; Hurst & Logue, 1970; Zipes & McIntosh, 1971). Such investigations have been performed both to determine the physiological significance of atrial transport (Jochim, 1938; Brockman, 1963; Skinner et al, 1963; Mitchell et al, 1965; Lord et al, 1969), and also with a view towards clinical application by atrial triggered or bifocal pacing (Nathan et al, 1963; Castillo et al, 1971).
Characterization of the dsDNA prophage sequences in the genome of Neisseria gonorrhoeae and visualization of productive bacteriophage (2007)

These data suggest that the genes similar to dsDNA lysogenic phage present in the gonococcus are generally conserved in this pathogen and that they are able to regulate the expression of other neisserial genes. Since phage particles were only present in culture supernatants after induction with mitomycin C, it indicates that the gonococcus also regulates the expression of bacteriophage genes.
Cover Picture: Angew. Chem. Int. Ed. 6/2002 (2002)

The cover picture shows the electric eel, Electrophorus electricus, a source for commercially available acetylcholinesterase. In an experiment described by K. B. Sharpless and M. G. Finn and co-workers on pp. 1053–1057, a femtomolar inhibitor was assembled by the enzyme from a collection of building blocks containing azide and alkyne functional groups, shown floating in solution. The templated 1,3-dipolar cycloaddition reaction, producing the inhibitor, is represented by the flare of light at the center of the image.
The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly (2015)

Previously, we identified ISRIB as a potent inhibitor of the integrated stress response (ISR) and showed that ISRIB makes cells resistant to the effects of eIF2α phosphorylation and enhances long-term memory in rodents (Sidrauski et al., 2013). Here, we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2α and induced no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2α phosphorylation, SG formation, and cognitive loss.
Reversible conversion of nitroxyl anion to nitric oxide by superoxide dismutase. (1991)

Superoxide dismutase (SOD) rapidly scavenges superoxide (O2-) and also prolongs the vasorelaxant effects of nitric oxide (NO), thought to be the endothelium-derived relaxing factor. This prolongation has been ascribed to prevention of the reaction between O2- with NO. We report that SOD supports a reversible reduction of NO to NO-. When cyanamide and catalase were used to generate NO- in the presence of SOD, NO was measured by the conversion of HbO2 to MetHb. When SOD[Cu(I)] was exposed to NO anaerobically, NO- was trapped by MetHb forming nitrosylmyoglobin. When NO was generated by 3-morpholinosydnonimine hydrochloride in the presence of SOD, NO- or a similar reductant was formed, which reduced catalase compound II and promoted the formation of the catalase [Fe(III)]-NO complex. It is, therefore, conceivable that SOD may protect NO and endothelium-derived relaxing factor by a mechanism in addition to O2- scavenging and that NO- may be a physiologically important form of endothelium-derived relaxing factor.
Biochemical and genome sequence analyses of Megasphaera sp. strain DISK18 from dental plaque of a healthy individual reveals commensal lifestyle (2016)

Much of the work in periodontal microbiology in recent years has focused on identifying and understanding periodontal pathogens. As the majority of oral microbes have not yet been isolated in pure form, it is essential to understand the phenotypic characteristics of microbes to decipher their role in oral environment. In this study, strain DISK18 was isolated from gingival sulcus and identified as a Megasphaera species. Although metagenomics studies revealed Megasphaera species as a major group within the oral habitat, they have never been isolated in cultivable form to date. Therefore, we have characterized the DISK18 strain to better understand its role in the periodontal ecosystem. Strain Megasphaera sp. DISK18 displayed the ability to adhere and self-aggregate, which are essential requisite features for inhabiting and persisting in oral cavity. It also coaggregated with other pioneer oral colonizers like Streptococcus and Lactobacillus species but not with Veillonella. This behaviour points towards its role in the ecologic succession of a multispecies biofilm as an early colonizer. The absence of virulence determining genes as observed in whole genome sequence analysis coupled with an inability to degrade collagen reveals that Megasphaera sp. strain DISK18 is likely not a pathogenic species and emphasizes its commensal lifestyle.
Synthesis and Fungicidal Evaluation of 2-Arylphenyl Ether-3-(1H-1,2,4-triazol-1-yl)propan-2-ol Derivatives (2009)

A series of novel 2-arylphenyl ether-3-(1H-1,2,4-triazol-1-yl)propan-2-ol derivatives were designed and synthesized as candidate fungicides. The new compounds were identified by (1)H NMR spectroscopy and element analysis. Their antifungal activities were evaluated. They exhibited excellent antifungal activities against five common pathogens in comparison with the commercial fungicides tebuconazole and difenoconazole. The antifungal activities of three new triazole alcohol compounds were compared with those of tebuconazole and difenoconazole at a concentration of 1 mug/mL.
Comparative Analysis of Human Gut Microbiota by Barcoded Pyrosequencing (2008)

Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.
An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea (2012)

Progress in treatment of dyspnea has not matched progress in elucidating underlying mechanisms. There is a critical need for interdisciplinary translational research to connect dyspnea mechanisms with clinical treatment and to validate dyspnea measures as patient-reported outcomes for clinical trials.
KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience (2008)

2 Background: Efficacy analyses of the randomized phase III CRYSTAL trial have shown a significant improvement in progression-free survival (PFS), overall response, and curative surgery rate when adding cetuximab to FOLFIRI in the first-line treatment of mCRC. Furthermore, KRAS mutation status has recently been shown to relate to outcome in mCRC patients (pts) treated with cetuximab as a single agent or in combination with irinotecan. Efficacy analyses have been repeated to evaluate the influence of KRAS mutation status in first-line pts treated with FOLFIRI with or without cetuximab under controlled study conditions. Methods: Blocks from archived tumor material were available from 587 of 1198 of the total pt population. Isolation of genomic DNA was performed directly from slides (3×10 μm). Determination was done by qPCR-based KRAS mutation analysis of codons 12/13. The KRAS-evaluable pts (n=540) were analyzed statistically to evaluate treatment effect stratified by KRAS mutation status (wild-type [wt] or mutation [mt]) and the given randomization strata using Cox regression for PFS time (primary IRC evaluation) and the CMH test for best overall response. Results: The population with available tissue for KRAS analysis was representative of the overall ITT population. KRAS mt were detected in 35.6% (192/540) of pts with evaluable samples. A statistically significant difference in favor of cetuximab was seen in KRAS wt pts for PFS (p=0.0167; hazard ratio [HR] estimate 0.68 [95% CI: 0.051–0.934]) and best overall response (59.3% [cetuximab + FOLFIRI] vs 43.2% [FOLFIRI], p=0.0025). Subgroup analyses by KRAS mt status for cetuximab + FOLFIRI vs FOLFIRI showed no significant differences between treatment groups for PFS (p=0.75; HR estimate 1.07 [95% CI: 0.71–1.61]) or best overall response (p=0.46). Conclusions: This large analysis shows the predictive value of KRAS mutation status for treatment with cetuximab plus FOLFIRI in the first-line treatment of mCRC. The data demonstrate that treatment effect of cetuximab in pts with KRAS wt is significantly enhanced compared with standard chemotherapy alone, whereas pts with KRAS mt could not be shown to benefit from cetuximab treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck Merck Merck