gebhart/patrepeval huggingface dataset:
Metabolism of sulfur amino acids in Saccharomyces cerevisiae (1997)

Sulfur amino acid biosynthesis in Saccharomyces cerevisiae involves a large number of enzymes required for the de novo biosynthesis of methionine and cysteine and the recycling of organic sulfur metabolites. This review summarizes the details of these processes and analyzes the molecular data which have been acquired in this metabolic area. Sulfur biochemistry appears not to be unique through terrestrial life, and S. cerevisiae is one of the species of sulfate-assimilatory organisms possessing a larger set of enzymes for sulfur metabolism. The review also deals with several enzyme deficiencies that lead to a nutritional requirement for organic sulfur, although they do not correspond to defects within the biosynthetic pathway. In S. cerevisiae, the sulfur amino acid biosynthetic pathway is tightly controlled: in response to an increase in the amount of intracellular S-adenosylmethionine (AdoMet), transcription of the coregulated genes is turned off. The second part of the review is devoted to the molecular mechanisms underlying this regulation. The coordinated response to AdoMet requires two cis-acting promoter elements. One centers on the sequence TCACGTG, which also constitutes a component of all S. cerevisiae centromeres. Situated upstream of the sulfur genes, this element is the binding site of a transcription activation complex consisting of a basic helix-loop-helix factor, Cbf1p, and two basic leucine zipper factors, Met4p and Met28p. Molecular studies have unraveled the specific functions for each subunit of the Cbf1p-Met4p-Met28p complex as well as the modalities of its assembly on the DNA. The Cbf1p-Met4p-Met28p complex contains only one transcription activation module, the Met4p subunit. Detailed mutational analysis of Met4p has elucidated its functional organization. In addition to its activation and bZIP domains, Met4p contains two regulatory domains, called the inhibitory region and the auxiliary domain. When the level of intracellular AdoMet increases, the transcription activation function of Met4 is prevented by Met30p, which binds to the Met4 inhibitory region. In addition to the Cbf1p-Met4p-Met28p complex, transcriptional regulation involves two zinc finger-containing proteins, Met31p and Met32p. The AdoMet-mediated control of the sulfur amino acid pathway illustrates the molecular strategies used by eucaryotic cells to couple gene expression to metabolic changes.
Therapeutic potential of JAK2 inhibitors (2009)

The discovery of an activating tyrosine kinase mutation JAK2V617F in myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) has resulted in the development of JAK2 inhibitors, of which several are being evaluated in phase I/II clinical studies. It is important to recognize that because the V617F mutation is localized in a region outside the adenosine triphosphate (ATP)-binding pocket of JAK2 enzyme, ATP-competitive inhibitors of JAK2 kinase (like the current JAK2 inhibitors in the clinic) are not likely to discriminate between wild-type and mutant JAK2 enzymes. Therefore, JAK2 inhibitors, by virtue of their near equipotent activity against wild-type JAK2 that is important for normal hematopoiesis, may have adverse myelosuppression as an expected side effect, if administered at doses that aim to completely inhibit the mutant JAK2 enzyme. While they may prove to be effective in controlling hyperproliferation of hematopoietic cells in PV and ET, they may not be able to eliminate mutant clones. On the other hand, JAK inhibitors may have great therapeutic benefit by controlling the disease for patients with MPNs who suffer from debilitating signs (eg, splenomegaly) or constitutional symptoms (which presumably result from high levels of circulating cytokines that signal through JAK enzymes). Indeed, the primary clinical benefits observed so far in MF patients have been significant reduction is splenomegaly, elimination of debilitating disease-related symptoms, and weight gain. Most importantly, patients with and without the JAK2V617F mutation appear to benefit to the same extent. In this review we summarize current clinical experience with JAK2 inhibitors in MPNs.
21 Translational Control in Cells Infected with Influenza Virus and Reovirus (1996)

The two RNA viruses, influenza virus and reovirus, utilize dramatically distinct tactics to optimize the translation of viral messenger RNAs. Presented here is a comprehensive review of the strategies used by these two virus groups to ensure both the selective and efficient synthesis of viral proteins. Among other topics are a discussion of the virus-induced “host shutoff” and documentation of the mechanisms by which influenza virus and reovirus down-regulate the double-stranded RNA (dsRNA)-activated, interferon-induced protein kinase, PKR. INFLUENZA VIRUS Influenza virus is an enveloped, negative-stranded segmented RNA virus that causes a disease which is responsible for up to 70,000 deaths a year in the United States and in the worst epidemic years, has killed 20,000,000 worldwide. It is a highly cytopathic virus that interferes dramatically with host macromolecular synthesis. Unlike most nononcogenic RNA viruses, the influenza replicative cycle includes both a nuclear and cytoplasmic phase (Krug et al. 1989), and this has a definite influence on the translational strategies of the virus. In the early 1970s, it was recognized that a shutoff of host-cell protein synthesis occurs at times when viral proteins are maximally made (Lazarowitz et al. 1971; Skehel 1972). What was not appreciated at the time were the numerous and complex strategies required by influenza virus to accomplish these goals (Garfinkel and Katze 1993b, 1994). In terms of translational control, influenza virus has two major objectives, neither of which is unique to this virus (see Mathews, this volume): (1) to selectively translate viral mRNAs and stop the translation...
Spatial pattern of receptor expression in the olfactory epithelium. (1992)

A PCR-based strategy for amplifying putative receptors involved in murine olfaction was employed to isolate a member (OR3) of the seven-transmembrane-domain receptor superfamily. During development, the first cells that express OR3 appear adjacent to the wall of the telencephalic vesicle at embryonic day 10. The OR3 receptor is uniquely expressed in a subset of olfactory cells that have a characteristic bilateral symmetry in the adult olfactory epithelium. This receptor and its specific pattern of expression may serve a functional role in odor coding or, alternatively, may play a role in the development of the olfactory system.
Sequence selective double strand DNA cleavage by Peptide Nucleic Acid (PNA) targeting using nuclease S1 (1993)

A novel method for sequence specific double strand DNA cleavage using PNA (peptide nucleic acid) targeting is described. Nuclease S1 digestion of double stranded DNA gives rise to double strand cleavage at an occupied PNA strand displacement binding site, and under optimized conditions complete cleavage can be obtained. The efficiency of this cleavage is more than 10 fold enhanced when a tandem PNA site is targeted, and additionally enhanced if this site is in trans rather than in cis orientation. Thus in effect, the PNA targeting makes the single strand specific nuclease S1 behave like a pseudo restriction endonuclease.
The SMART automatic document retrieval systems—an illustration (1965)

A fully automatic document retrieval system operating on the IBM 7094 is described. The system is characterized by the fact that several hundred different methods are available to analyze documents and search requests. This feature is used in the retrieval process by leaving the exact sequence of operations initially unspecified, and adapting the search strategy to the needs of individual users.
Biofuel Cell Controlled by Enzyme Logic Systems (2008)

An enzyme-based biofuel cell with a pH-switchable oxygen electrode, controlled by enzyme logic operations processing in situ biochemical input signals, has been developed. Two Boolean logic gates (AND/OR) were assembled from enzyme systems to process biochemical signals and to convert them logically into pH-changes of the solution. The cathode used in the biofuel cell was modified with a polymer-brush functionalized with Os-complex redox species operating as relay units to mediate electron transport between the conductive support and soluble laccase biocatalyzing oxygen reduction. The electrochemical activity of the modified electrode was switchable by alteration of the solution pH value. The electrode was electrochemically mute at pH > 5.5, and it was activated for the bioelectrocatalytic oxygen reduction at pH < 4.5. The sharp transition between the inactive and active states was used to control the electrode activity by external enzymatic systems operating as logic switches in the system. The enzyme logic systems were decreasing the pH value upon appropriate combinations of the biochemical signals corresponding to the AND/OR Boolean logic. Then the pH-switchable electrode was activated for the oxygen reduction, and the entire biofuel cell was switched ON. The biofuel cell was also switched OFF by another biochemical signal which resets the pH value to the original neutral value. The present biofuel cell is the first prototype of a future implantable biofuel cell controlled by complex biochemical reactions to deliver power on-demand responding in a logical way to the physiological needs.
A Comparison of Immediate Angioplasty with Thrombolytic Therapy for Acute Myocardial Infarction (1993)

As compared with t-PA therapy for acute myocardial infarction, immediate PTCA reduced the combined occurrence of nonfatal reinfarction or death, was associated with a lower rate of intracranial hemorrhage, and resulted in similar left ventricular systolic function.
CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants (2002)

Over 40 cytochrome P450 (CYP) 2D6 allelic variants have been discovered thus far. The alleles may be classified on the basis of the level of activity for which they encode CYP2D6 enzymes, into functional, non-functional and reduced function groups. CYP2D6 allele frequency is known to vary amongst racial/ethnic groups. Generally, for European Caucasians and their descendants, the functional group of alleles are predominant, with a frequency of 71%. Non-functional alleles represent 26% of the variability, mainly CYP2D6*4. In Asians and their close descendants, functional alleles represent only ~ 50% of the frequency of CYP2D6 alleles. Asians and Pacific Islanders have a high frequency (median = 41%) of a reduced function allele, CYP2D6*10, contributing to the population shift to the right of metabolic rates indicating slower metabolism. Information concerning Amerindians from North (Canada), Central and South America indicate comparatively low frequencies of CYP2D6*10, perhaps a "founders" effect. The frequency of functional alleles in Africans and African Americans is also about 50%. Both Africans and African Americans have reduced function alleles representing 35% of allele variation, mainly CYP2D6*17. African Americans, however, have more than twice the median frequency of nonfunctional alleles compared with Africans (14.5% vs 6.3%). Non-functional and reduced function alleles represent about 50% of allele frequency in Black populations but a much greater variety than carried in Asians. Since alleles which encode for no or reduced functioning clearly affect metabolic activity of drugs mediated by CYP2D6, studies are needed in populations in which these alleles play a major role in order to assure optimal dosing recommendations are based on empirical pharmacogenetics.
Graphes d'événements stochastiques : temps de cycle moyen et marquage (1991)

Dans ce papier, nous considérons un type particulier de réseaux de Petri appelé graphes d'événements temporisés. Nous examinons le cas où les temps de franchissement sont aléatoires et bornés. Le but est d'obtenir un temps de cycle moyen aussi petit que possible en utilisant un nombre donné de jetons. Nous montrons que sous certaines conditions, la diminution la plus importante du temps de cycle moyen est obtenue lorsqu'on ajoute un jeton dans le circuit élémentaire qui a le temps de cycle moyen le plus grand. Nous illustrons ce résultat avec un exemple.
Structural Analysis of Arabidopsis thaliana Chromosome 5. X. Sequence Features of the Regions of 3,076,755 bp Covered by Sixty P1 and TAC Clones (2000)

In our ongoing project to deduce the nucleotide sequence of Arabidopsis thaliana chromosome 5, non-redundant P1 and TAC clones have been sequenced on the basis of the fine physical map, and as of January, 2000, the sequences of 16.6 Mb representing approximately 60% of chromosome 5 have been accumulated and released at our web site. Along with the sequence determination, structural features of the sequenced regions have been analyzed by applying a variety of computer programs, and we already predicted a total of 2697 potential protein coding genes in the 11,166,130 bp regions, which are covered by 159 P1 and TAC clones. In this paper, we describe the structural features of the 3,076,755 bp regions covered by newly analyzed 60 P1 and TAC clones. A total of 715 potential protein coding genes were identified, giving an average density of the genes identified of 1 gene per 4001 bp. Introns were observed in 80% of the genes, and the average number per gene and the average length of the introns were 4.5 and 147 bp, respectively. These sequence features are nearly identical to those in our latest report in which the data were compiled based on a new standard of gene assignment including the computer-predicted hypothetical genes. The regions also contained 12 tRNA genes when searched by similarity to reported tRNA genes and the tRNA scan-SE program. The sequence data and information on the potential genes are available through the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/kaos/.
Identification of a novel protein, LYRIC, localized to tight junctions of polarized epithelial cells (2004)

Tight junctions (TJ) are multiprotein complexes that function to regulate paracellular transport of molecules through epithelial and endothelial cell layers. Many new tight junction-associated proteins have been identified in the past few years, and their functional roles and interactions have just begun to be elucidated. In this paper, we describe a novel protein LYsine-RIch CEACAM1 co-isolated (LYRIC) that is widely expressed and highly conserved between species. LYRIC has no conserved domains that would indicate function and does not appear to be a member of a larger protein family. Data from analysis of rat and human tissue sections and cell lines show that LYRIC colocalizes with tight junction proteins ZO-1 and occludin in polarized epithelial cells, suggesting that LYRIC is part of the tight junction complex. LYRIC dissociates from ZO-1 when junctional complexes are disrupted, and as tight junctions reform, ZO-1 relocalizes before LYRIC. These results suggest that LYRIC is most likely not a structural component required for TJ formation, but rather is recruited during the maturation of the tight junction complex.
Gallotannins Inhibit Growth, Water-insoluble Glucan Synthesis, and Aggregation of Mutans Streptococci (1988)

During screening for anti-plaque agents of plant origin, ethanolic extracts from Melaphis chinensis (Bell), the Chinese Nutgall, exhibited strong inhibition of glucosyltransferase (GTF), in vitro adherence and glucan-induced agglutination of Streptococcus mutans 3209 and S. sobrinus B13. More than 91% inhibition of water-insoluble glucan synthesis from sucrose by GTF was noted at a concentration as low as 7.8 micrograms/mL. Bactericidal effects on other mutans streptococci, S. salivarius, and Actinomyces viscosus were also evident. Through chemical fractionation and analyses, along with bioassays, the active components were identified as gallotannins.
RF-wafer scale integration: a new approach to active phased arrays (2002)

Active phased array antennas utilize individually packaged transmit/receive modules, which provide both transmitter and receiver functions on /spl lambda/2 wavelength centers. Such modules usually contain 5 to 7 individual GaAs circuits which provide the following functions: transmit amplifier, phase shifter, variable attenuator, T/R switch, and low noise amplifier. The authors describe ongoing efforts in which many T/R modules are fabricated simultaneously on a single 3-inch GaAs-wafer. Redundancy in circuit elements is utilized to obtain high yield. The resulting wafer of GaAs T/R cells is utilized as a layer within a more complex package that includes the individual radiating element. Efforts to date have focused on technology for 2-20 GHz and upon extending the technology to higher frequencies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A new retrovirus packaging cell for gene transfer constructed from amplified long terminal repeat-free chimeric proviral genes (1992)

The retroviral gene transfer system is a powerful tool for somatic gene therapy. A retroviral stock with a high viral titer and lacking replication-competent virus (RCV) is desirable for this type of gene transfer. To fulfill these requirements, we made a new packaging cell line, designated ampli-GPE. To reduce the homology between proviral DNA in the packaging cell and retroviral vector, the gag-pol and env genes of Moloney murine leukemia virus were separated onto two different plasmids, pGP-KV and pENV-KV, respectively, in which the 5' long terminal repeat and the 3' long terminal repeat had been replaced by the mouse metallothionein I promoter or the human beta-globin gene containing the polyadenylation site as control units for the gag-pol and env genes. In addition, these plasmids contained 69% of the bovine papillomavirus gene for gene amplification to obtain production of virus at a high titer. NIH 3T3 clones containing approximately 20 to 50 copies of the gag-pol and env genes were selected and designated ampli-GPE. When ampli-GPE was transfected with the N2 vector or pZipNeoSV(DHFR) derived from pZipNeoSV(X)1, we established clones producing titers of 5 x 10(6) and 1 x 10(6) CFU/ml, respectively. There was no sign of RCV generation in any virus-producing cells from ampli-GPE. However, virus-producing cells derived from psi 2 cells transfected with N2 did generate RCV. Thus, we showed that ampli-GPE, possessing the minimum complement of proviral genes, has potential for the development of a gene transfer system.
Single dose pharmacokinetics and bioavailability of butyryl glucosamine in the rat. (2002)

GLcNBu has rapid but low absorption and is widely distributed and efficiently cleared. The gut rather than liver is mainly responsible for the low bioavailability of GLcNBu. Limited absorption of GLcNBu suggests a transport dependent absorption. Food does not significantly affect the bioavailability of GLcNBu.
ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins. (1986)

The MgATP binding site of adenylate kinase, located by a combination of NMR and x-ray diffraction, is near three protein segments, five to seven amino acids in length, that are homologous in sequence to segments found in other nucleotide-binding phosphotransferases, such as myosin and F1-ATPase, ras p21 and transducin GTPases, and cAMP-dependent and src protein kinases, suggesting equivalent mechanistic roles of these segments in all of these proteins. Segment 1 is a glycine-rich flexible loop that, on adenylate kinase, may control access to the ATP-binding site by changing its conformation. Segment 2 is an alpha-helix containing two hydrophobic residues that interact with the adenine-ribose moiety of ATP, and a lysine that may bind to the beta- and gamma-phosphates of ATP. Segment 3 is a hydrophobic strand of parallel beta-pleated sheet, terminated by a carboxylate, that flanks the triphosphate binding site. The various reported mutations of ras p21 that convert it to a transforming agent all appear to involve segment 1, and such substitutions may alter the properties of p21 by hindering a conformational change at this segment. In F1-ATPase, the flexible loop may, by its position, control both the accessibility and the ATP/ADP equilibrium constant on the enzyme.
AN ANTIMALARIAL ALKALOID FROM HYDRANGEA. IX. SYNTHESIS OF 3-[β-KETO-γ-(4-HYDROXY-2-PIPERIDYL)PROPYL]-4-QUINAZOLONE, AN ISOMER (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAN ANTIMALARIAL ALKALOID FROM HYDRANGEA. IX. SYNTHESIS OF 3-[β-KETO-γ-(4-HYDROXY-2-PIPERIDYL)PROPYL]-4-QUINAZOLONE, AN ISOMERB. R. BAKER, ROBERT E. SCHAUB, MERLE V. QUERRY, and JAMES H. WILLIAMSCite this: J. Org. Chem. 1952, 17, 1, 97–108Publication Date (Print):January 1, 1952Publication History Published online1 May 2002Published inissue 1 January 1952https://pubs.acs.org/doi/10.1021/jo01135a010https://doi.org/10.1021/jo01135a010research-articleACS PublicationsRequest reuse permissionsArticle Views131Altmetric-Citations14LEARN 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
Effectiveness of a Dot-Blot Immunoassay of Anti-Rickettsia tsutsugamushi Antibodies for Serologic Analysis of Scrub Typhus (1995)

We compared a commercially available dot-blot immunoassay system with the indirect immunofluorescence assay (IFA) in tests of known negative and known positive sera from scrub typhus cases. Using a panel of 100 sera from patients with various rickettsial and nonrickettsial infections, we observed that the IFA was 99% specific and the dipstick assay was 98% specific. In tests of 91 sera (30 negative and 61 positive for scrub typhus antibodies) from a study of febrile patients in Malaysia, using the standard of an IFA titer < 1:64 as negative, an IFA titer > 1:128 as positive, and an IFA titer = 1:64 as either positive or negative (supported by clinical records), dipsticks were 83% specific and 90% sensitive. The quantitative correlation of the dipsticks to IFA titers was confirmed by significant differences in geometric means of inverse IFA titers corresponding to the number of positive dipstick spots (no dots = 8.5, one dot = 43.3, two dots = 206.7, and three dots = 676.9). The assay would enable physicians and public health workers who deal with patients to quickly diagnose and appropriately treat most cases of the disease, especially in areas of high prevalence where the proportion of false-positive results to true-positive results would be low.