gebhart/patrepeval huggingface dataset:
Factor IXHollywood: substitution of Pro55 by Ala in the first epidermal growth factor-like domain (1990)

Factor IX is a multidomain protein essential for hemostasis. We describe a mutation in a patient affecting the first epidermal growth factor (EGF)-like domain of the protein. All exons and the promoter region of the gene were amplified by the polymerase chain reaction method, and sequenced. Only a single mutation (C----G), that predicts the substitution of Pro55 by Ala in the first EGF domain was found in the patient's gene. This mutation leads to new restriction sites for four enzymes. One new site (Nsi) was tested in the amplified exon IV fragment and was shown to provide a rapid and reliable marker for carrier detection and prenatal diagnosis in the affected family. The factor IX protein, termed factor IXHollywood (IXHW), was isolated to homogeneity from the patient's plasma. As compared with normal factor IX (IXN), IXHW contained the same amount of gamma-carboxy glutamic acid but twice the amount of beta-OH aspartic acid. Both IXHW and IXN contained no detectable free -SH groups. Further, IXHW could be readily cleaved to yield a factor IXa-like molecule by factor Xla/Ca2+. However, IXaHW (compared with IXaN) activated factor X approximately twofold slower in the presence of Ca2+ and phospholipid (PL), and 8- to 12-fold slower in the presence of Ca2+, PL, and factor VIIIa. Additionally, IXaHW had only approximately 10% of the activity of IXaN in an aPTT assay. In agreement with the nuclear magnetic resonance- derived structure of EGF, the Chou-Fasman algorithm strongly predicted a beta turn involving residues Asn-Pro55-Cys-Leu in IXN. Replacement of Pro55 by Ala gave a fourfold decrease in the beta turn probability for this peptide, suggesting a change(s) in the secondary structure in the EGF domain of IXHW. Since this domain of IXN is thought to have one high-affinity Ca2+ binding site and may be involved in PL and/or factor VIIIa binding, the localized secondary structural changes in IXHW could lead to distortion of the binding site(s) for the cofactor(s) and, thus, a dysfunctional molecule.
Exon amplification: a strategy to isolate mammalian genes based on RNA splicing. (1991)

We have developed a method, exon amplification, for fast and efficient isolation of coding sequences from complex mammalian genomic DNA. This method is based on the selection of RNA sequences, exons, which are flanked by functional 5' and 3' splice sites. Fragments of cloned genomic DNA are inserted into an intron, which is flanked by 5' and 3' splice sites of the human immunodeficiency virus 1 tat gene contained within the plasmid pSPL1. COS-7 cells are transfected with these constructs, and the resulting RNA transcripts are processed in vivo. Splice sites of exons contained within the inserted genomic fragment are paired with splice sites of the flanking tat intron. The resulting mature RNA contains the previously unidentified exons, which can then be amplified via RNA-based PCR and cloned. Using this method, we have isolated exon sequences from cloned genomic fragments of the murine Na,K-ATPase alpha 1-subunit gene. We have also screened randomly selected genomic clones known to be derived from a segment of human chromosome 19 and have isolated exon sequences of the DNA repair gene ERCC1. The sensitivity and ease of the exon amplification method permit screening of 20-40 kilobase pairs of genomic DNA in a single transfection. This approach will be extremely useful for rapid identification of mammalian exons and the genes from which they are derived as well as for the generation of chromosomal transcription maps.
Aluminium in the neonate related to parenteral nutrition (1994)

Sources of aluminium loading and exposure in preterm and full-term newborns were studied. Parenteral nutrition solutions were the main source of aluminium representing 88.7% of total aluminium intake. Blood and urine aluminium levels were followed over a 28-day period in a group of 26 preterm and 9 term infants while receiving parenteral nutrition (duration 15.6 +/- 8.7 days) and later when being formula fed. Urine levels were followed up to 13 weeks in a subgroup of the neonates. Serum aluminium levels (0.86 +/- 0.38 mumol/l) and urine aluminium/creatinine ratio (1.52 +/- 0.81 mumol/mmol) were increased when the infants were receiving parenteral nutrition compared with the control group (p < 0.001). The urine aluminium/creatinine ratio remained high up to 10 weeks following withdrawal of parenteral nutrition and suggested tissular loading. This was confirmed after high aluminium levels were found in post-mortem brain and bone samples from two preterm and one full-term infant. We conclude that both preterm and full-term neonates are susceptible to accumulation of aluminium in tissue while receiving parenteral nutrition.
Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer (2014)

The microencapsulation of 3-BrPA represents a promising step towards achieving the goal of systemically deliverable antiglycolytic tumor therapy. The strong anticancer effects of β-CD-3-BrPA combined with its favorable toxicity profile suggest that clinical trials, particularly in patients with PDAC, should be considered.
The copper-catalyzed redox reaction between aqueous hydrogen peroxide and hydrazine. I. New experimental results and observations (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe copper-catalyzed redox reaction between aqueous hydrogen peroxide and hydrazine. I. New experimental results and observationsYaping Zhong and Phooi K. LimCite this: J. Am. Chem. Soc. 1989, 111, 22, 8398–8404Publication Date (Print):October 1, 1989Publication History Published online1 May 2002Published inissue 1 October 1989https://pubs.acs.org/doi/10.1021/ja00204a011https://doi.org/10.1021/ja00204a011research-articleACS PublicationsRequest reuse permissionsArticle Views467Altmetric-Citations15LEARN 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
A status report on RNAi therapeutics (2010)

Fire and Mello initiated the current explosion of interest in RNA interference (RNAi) biology with their seminal work in Caenorhabditis elegans. These observations were closely followed by the demonstration of RNAi in Drosophila melanogaster. However, the full potential of these new discoveries only became clear when Tuschl and colleagues showed that 21-22 bp RNA duplexes with 3" overhangs, termed small interfering (si)RNAs, could reliably execute RNAi in a range of mammalian cells. Soon afterwards, it became clear that many different human cell types had endogenous machinery, the RNA-induced silencing complex (RISC), which could be harnessed to silence any gene in the genome. Beyond the availability of a novel way to dissect biology, an important target validation tool was now available. More importantly, two key properties of the RNAi pathway - sequence-mediated specificity and potency - suggested that RNAi might be the most important pharmacological advance since the advent of protein therapeutics. The implications were profound. One could now envisage selecting disease-associated targets at will and expect to suppress proteins that had remained intractable to inhibition by conventional methods, such as small molecules. This review attempts to summarize the current understanding on siRNA lead discovery, the delivery of RNAi therapeutics, typical in vivo pharmacological profiles, preclinical safety evaluation and an overview of the 14 programs that have already entered clinical practice.
Distribution and metabolism of maternal progesterone in the uterus, placenta, and fetus during rat pregnancy (1995)

This study examined the in vivo distribution and metabolism of maternal progesterone (P4) in the rat uterus at Day 16 of pregnancy, i.e., the time of maximal P4 secretion, and at Day 22, one day prior to parturition. Arterial and uterine venous blood samples were collected at 20-min intervals from rats (n = 5 per group) infused with [3H]-P4 for 2 h. Placentas, fetuses, and uterine tissue (myometrium and decidua) were obtained just prior to the end of the infusion; and total tritium, [3H]-P4, and lipid-soluble and water-soluble metabolite concentrations were determined in all blood and tissue samples. Irreversible extraction of P4 by the uterus and its contents was 54.2 +/- 6.0% (mean +/- SEM) on Day 16, and this was at least maintained to Day 22 (64.7 +/- 7.4%). Because uterine blood flow increases dramatically over this period, the maintenance of high uterine P4 extraction is likely to have contributed partly to the 41% rise in the metabolic clearance rate of P4 between Day 16 (147 +/- 16 ml/min per kg) and Day 22 (207 +/- 13 ml/min per kg). Uterine tissue levels of [3H]-P4 exceeded (1.6-fold) those in arterial blood on Day 16, but this difference was not evident at Day 22. In contrast, the concentration of [3H]-P4 in the placenta was lower than that in arterial blood at Day 16 (66% lower) and Day 22 (25% lower), even though total tritium concentrations were similar at these sites. [3H]-P4 was also lower in fetal tissue compared with maternal arterial blood on both days of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Modulation of asymmetric cell division as a mechanism to boost CD8 + T cell memory (2019)

Asymmetric partitioning of fate determinants is a mechanism that contributes to T cell differentiation. However, it remains unclear whether the ability of T cells to divide asymmetrically is influenced by their differentiation state, as well as whether enforcing asymmetric cell division (ACD) rates would have an impact on T cell differentiation and memory formation. Using the murine LCMV infection model, we established a correlation between cell stemness and the ability of CD8<sup>+</sup> T cells to undergo ACD. Transient mTOR inhibition was proven to increase ACD rates in naïve and memory cells and to install this ability in exhausted CD8<sup>+</sup> T cells. Functionally, enforced ACD correlated with increased memory potential, leading to more efficient recall response and viral control upon acute or chronic LCMV infection. Moreover, transient mTOR inhibition also increased ACD rates in human CD8<sup>+</sup> T cells. Transcriptional profiling revealed that progenies emerging from enforced ACD exhibited more pronounced early memory signatures, which functionally endowed these cells with better survival in the absence of antigen exposure and more robust homing to secondary lymphoid organs, providing critical access to survival niches. Our data provide important insights into how ACD can improve long-term survival and function of T cells and open new perspectives for vaccination and adoptive T cell transfer therapies.
Introduction (1995)

Although all levels of education have been affected by the changes of the last six or seven years, perhaps none has faced a greater challenge than higher education. This is illustrated in V. A. Radaev's report on a survey of university and college instructors that was conducted in six cities in the spring of 1994. According to respondents, finding and keeping well-qualified teachers will be difficult during the next few years, especially in those institutions not considered among the elite. While at present there are attempts to use material rewards where possible to recruit and retain the best faculty and graduate students, not all colleges and universities have the resources to do this, especially when they have to compete with the more lucrative salary levels found in the private sector. A more detailed picture is presented by Kharcheva and Sheregi in "Higher Education in the Mirror of Sociology."
The repair of speech act misunderstandings by abductive inference (1995)

During a conversation, agents can easily come to have different beliefs about the meaning or discourse role of some utterance. Participants normally rely on their expectations to determine whether the conversation is proceeding smoothly: if nothing unusual is detected, then understanding is presumed to occur. Conversely, when an agent says something that is inconsistent with another's expectations, then the other agent may change her interpretation of an earlier turn and direct her response to the reinterpretation, accomplishing what is known as a fourth-turn repair.Here we describe an abductive account of the interpretation of speech acts and the repair of speech act misunderstandings. Our discussion considers the kinds of information that participants use to interpret an utterance, even if it is inconsistent with their beliefs. It also considers the information used to design repairs. We describe a mapping between the utterance-level forms (semantics) and discourse-level acts (pragmatics), and a relation between the discourse acts and the beliefs and intentions that they express. We specify for each discourse act, the acts that might be expected, if the hearer has understood the speaker correctly. We also describe our account of belief and intention, distinguishing the beliefs agents actually have from the ones they act as if they have when they perform a discourse act. To support repair, we model how misunderstandings can lead to unexpected actions and utterances and describe the processes of interpretation and repair. To illustrate the approach, we show how it accounts for an example repair.
Diet-dependent hypercalciuria in transgenic mice with reduced CLC5 chloride channel expression (1999)

Dent's disease is an X-linked inherited disorder characterized by hypercalciuria, nephrocalcinosis, nephrolithiasis, low molecular weight proteinuria, Fanconi's syndrome, and renal failure. It is caused by inactivating mutations in CLC5, a member of the CLC voltage-gated chloride channel family. CLC5 is known to be expressed in the endosomal compartment of the renal proximal tubule, where it may be required for endosomal acidification and trafficking. Although the Fanconi's syndrome and low molecular weight proteinuria in Dent's disease can be explained by disruption of endosomal function in this nephron segment, the pathogenesis of the hypercalciuria in this disease is unknown. We have generated transgenic mice (RZ) with reduced CLC5 expression by introduction of an antisense ribozyme targeted against CLC5. RZ mice are markedly hypercalciuric compared with nontransgenic control mice, at a time when their serum electrolytes and renal function are otherwise normal. This suggests that hypercalciuria in Dent's disease is a direct consequence of CLC5 hypofunction and is not attributable to a gain of function by mutant CLC5, an effect of modifier genes, or a secondary result of nonspecific renal injury. Surprisingly, hypercalciuria in RZ mice is abolished by dietary calcium deprivation, suggesting that the hypercalciuria may be attributable to gastrointestinal hyperabsorption of calcium rather than a renal calcium leak.
Frequency and Distribution of DNA Uptake Signal Sequences in the Haemophilus influenzae Rd Genome (1995)

The naturally transformable, Gram-negative bacterium Haemophilus influenzae Rd preferentially takes up DNA of its own species by recognizing a 9-base pair sequence, 5'-AAGTGCGGT, carried in multiple copies in its chromosome. With the availability of the complete genome sequence, 1465 copies of the 9-base pair uptake site have been identified. Alignment of these sites unexpectedly reveals an extended consensus region of 29 base pairs containing the core 9-base pair region and two downstream 6-base pair A/T-rich regions, each spaced about one helix turn apart. Seventeen percent of the sites are in inverted repeat pairs, many of which are located downstream to gene termini and are capable of forming stem-loop structures in messenger RNA that might function as signals for transcription termination.
Management discourse and action (2006)

An exploration of the effects on organisational change projects of the dissonance between the management discourse of enterprising, self reliant teams and the centralised decision making characteristic of corporatised universities.
Laser fluorometric detection in liquid chromatography (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLaser fluorometric detection in liquid chromatographyEdward S. Yeung and Michael J. SepaniakCite this: Anal. Chem. 1980, 52, 13, 1465–1481Publication Date (Print):November 1, 1980Publication History Published online21 September 2008Published inissue 1 November 1980https://doi.org/10.1021/ac50063a003RIGHTS & PERMISSIONSArticle Views77Altmetric-Citations55LEARN 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 PDF (1 MB) Get e-Alerts Get e-Alerts
Genetic Analysis of Brown Stem Rot Resistance in Soybean (1989)

Genetic resistance of soybean [ Glycine max (L.) Merr.] to Phialophora gregata (Allington and Chamberlain) W. Gains, the cause of brown stem rot (BSR), can reduce yield losses in northern USA and Canadian production regions. Although two major dominant genes have been identified, additional sources of resistance may provide higher levels of resistance and/or more stable resistance over environments. The objectives of this study were to: (i) determine the pattern of inheritance of the BSR resistance found in PI 437970 and (ii) study allelic relationships of resistance genes in PI 437970 with Rbs 1 , and Rbs 2 . Evaluations were conducted using a root dip inoculation method in the field and greenhouse. The F 2 and F 3 plants were classified as resistant or susceptible based on mean parental reactions. Segregating generations of the cross PI 437970 ✕ ‘Pioneer Variety P9271’ revealed a single dominant gene conditioning BSR resistance. Crosses of PI 437970 with L78‐4094 ( Rbs 1 and PI 437833 ( Rbs 2 ) each demonstrated duplicate dominant epistasis indicating a third distinct gene designated Rbs 3 .
Single-chip 4×500-MBd CMOS transceiver (1996)

A CMOS chip containing four 500-MBd serializer/deserializer pairs has been designed to relieve interconnect congestion in an ATM switch system. The 9.7/spl times/9.7 mm/sup 2/ chip fabricated in a 0.8-/spl mu/m technology is packaged on a ceramic ball grid array and dissipates 3.5 W. It replaces a 72-wire parallel interface with an eight-line serial interface transparent to the user and supports transmission at 1.6 Gb/s per direction in full-duplex mode. Virtually error-free operation in a system environment over electrical serial links having up to 9 dB loss at 500 MHz has been realized using signal predistortion for the serial bit stream and PLL clock recovery for each of the four receivers. Interface timing and serial-link driver strength are programmable.
Cynomolgus monkey testicular cDNAs for discovery of novel human genes in the human genome sequence (2002)

In this report, we determined 302 full-insert sequences of cynomolgus monkey cDNAs with enough length of open reading frames to discover novel transcripts as human homologues. Among 302 cDNA sequences, human homologues of 89 cDNAs have not been predicted in the annotated human genome sequence in the Ensembl. Additionally, we identified 75 dominantly expressed genes in testis among the full-sequenced clones by using a DNA microarray. Our cDNA clones and analytical results will be valuable resources for future functional genomic studies.
Core Organic Chemistry (1999)

General Organic Chemistry. Alkanes. Alkenes. Alkynes. Alcohols and Thiols. Ethers and Sulfides. Epoxides. Alkyl Halides. Amines. The Carbonyl Group. Aromaticity: The Chemistry of Benzene and Derivatives. Appendix. References. Index.
Genetic Evaluation of Holstein Bulls for Somatic Cells in Milk of Daughters (1992)

Lactational means of somatic cell score from sample days of primiparous DHI cows were analyzed to compare dairy records processing centers for data properties, to examine effects of age at calving and month of calving on somatic cell score, and to calculate preliminary PTA of sires for somatic cell scores. Five processing centers contributed data but differed substantially with respect to availability of records in progress, DIM on last sample day, and length of time that data were submitted. Highest lactational means of somatic cell score tended to be in short lactations for young cows but in long lactations for older cows. Regions of the country differed substantially for effect of month of calving on lactational means of somatic cell score, but lactational means of somatic cell scores increased with age at calving for all dairy records processing centers. Standardized yields of milk, fat, and protein were included as multiple traits with somatic cell score for analysis. Heritability of somatic cell score was .08 to .16 for individual processing centers and .10 across processing centers. Phenotypic correlations of somatic cell score with yield traits were negative, but genetic correlations were positive. Selection for decreased somatic cell score on a national basis should be possible and would seem advisable to decrease mastitis infections. Response may be slow, however, because of antagonistic genetic relationships with the yield traits, which have great economic importance.
De novo DNA synthesis using single molecule PCR (2008)

The throughput of DNA reading (sequencing) has dramatically increased recently due to the incorporation of in vitro clonal amplification. The throughput of DNA writing (synthesis) is trailing behind, with cloning and sequencing constituting the main bottleneck. To overcome this bottleneck, an in vitro alternative for in vivo DNA cloning must be integrated into DNA synthesis methods. Here we show how a new single molecule PCR (smPCR)-based procedure can be employed as a general substitute to in vivo cloning thereby allowing for the first time in vitro DNA synthesis. We integrated this rapid and high fidelity in vitro procedure into our earlier recursive DNA synthesis and error correction procedure and used it to efficiently construct and error-correct a 1.8-kb DNA molecule from synthetic unpurified oligos completely in vitro. Although we demonstrate incorporating smPCR in a particular method, the approach is general and can be used in principle in conjunction with other DNA synthesis methods as well.