gebhart/patrepeval huggingface dataset:
O1‐06‐01: Apoeϵ3 A3nd Tomm‐40 Haplotypes Determine Inheritance of Alzheimer's Disease Independently of Apoeϵ4 Risk (2009)

The association of apolipoprotein E (APOE) genotypes, particularly APOE ϵ4 (APOE4), with the risk and age of onset of Alzheimer's disease (AD) remains the most confirmed genetic association for any complex disease. Estimates of the heritability of APOE4 for late onset AD range from 58% to 79%, and the population attributable risk due to the APOE4 allele is between 20% and 70%. These estimates suggest that other genetic variants and/or interactions between variants incur additional disease risk and modify age of onset distributions. Genome wide scan association results for AD have consistently reproduced the extraordinary association of the LD region containing APOE. TOMM40, the protein translocase of the outer mitochondrial membrane, is in high LD with APOE, and codes for the membrane channel through which cytoplasmic peptides and proteins traverse in order to synthesize new mitochondria. Our objectives were to identify additional haplotypes within the LD region that increase the estimates of heritability. We examined the LD region containing both APOE and TOMM40 using deep (10X) primary sequencing in AD patients and controls. We performed phylogenetic analyses of the LD region covering TOMM40 and APOE in 66 patients and 66 age-matched controls with respect to risk and age of onset distribution. We found that unique and distinct inherited families of different TOMM40 variants are located on the same genomic interval as APOE3, but not on the APOE4-containing genomic interval and can either increase or decrease the age of risk distribution of AD. Therefore the genetic inheritance of these TOMM40 variants are independent of the inheritance of APOE4, effectively providing a differentiation of two distinct forms of APOE3 - those linked to TOMM40 haplotypes that increase riskand decrease age of onset, and those that decrease risk. These data increase the accuracy of genetic age of onset risk, dependent on age, APOE and TOMM40 genotypes and provide the opportunity to define high risk of AD over the next 5-7 years, versus lower risk of AD. The prospective predictive validation of this predictive diagnostic is planned to be performed simultaneously with an AD prevention clinical trial [Zinfandel Pharma].
A review of feature selection techniques in bioinformatics (2007)

Feature selection techniques have become an apparent need in many bioinformatics applications. In addition to the large pool of techniques that have already been developed in the machine learning and data mining fields, specific applications in bioinformatics have led to a wealth of newly proposed techniques. In this article, we make the interested reader aware of the possibilities of feature selection, providing a basic taxonomy of feature selection techniques, and discussing their use, variety and potential in a number of both common as well as upcoming bioinformatics applications.
Clinical use of extended-release oral treprostinil in the treatment of pulmonary arterial hypertension (2016)

The development of parenteral prostacyclin therapy marked a dramatic breakthrough in the treatment of pulmonary arterial hypertension (PAH). Intravenous (IV) epoprostenol was the first PAH specific therapy and to date, remains the only treatment to demonstrate a mortality benefit. Because of the inherent complexities and risks of treating patients with continuous infusion IV therapy, there is great interest in the development of an oral prostacyclin analog that could mimic the benefits of IV therapy. Herein, we highlight the development of oral prostacyclin therapy, focusing on oral treprostinil, the only US Food and Drug Administration approved oral prostacyclin. Recent Phase III clinical trials have shown the drug to improve exercise tolerance in treatment-naïve PAH patients, but not patients on background oral therapy. Oral treprostinil appears to be most efficacious at higher doses, but its side effect profile and complexities with dosing complicate its use. While oral treprostinil's current therapeutic role in PAH remains unclear, ongoing studies of this class of medication should help clarify their role in the treatment of PAH.
Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer (2012)

In previous work we transferred a human factor IX-encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier who died of causes unrelated to gene transfer. Using Western blot, IHC, and immunofluorescent staining, we show persistent factor IX expression in injected muscle tissue. F.IX transcripts were detected in injected skeletal muscle using RT-PCR, and isolated whole genomic DNA tested positive for the presence of the transferred AAV vector sequence. This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer.
Complete DNA sequence, specific Tn5 insertion map, and gene assignment of the carotenoid biosynthesis pathway of Rhodobacter sphaeroides (1995)

The carotenoid biosynthesis genes form a cluster within the genome of Rhodobacter sphaeroides, lying in the middle of a larger cluster and 45 kb in length, which contains genes for bacteriochlorophyll biosynthesis and for the reaction center and light-harvesting apoproteins. The positions and approximate limits of the carotenoid genes were determined previously by localized transposon Tn5 mutagenesis and by comparison with the closely related Rhodobacter capsulatus carotenoid gene cluster. In this report, analysis of the DNA and deduced amino acid sequences of the carotenoid genes in R. sphaeroides are presented. Twenty-five Tn5 insertion mutants were used to produce a base-specific Tn5 insertion map of this region, and carotenoid gene assignment was supported by spectroscopic, ultrastructural, and high-pressure liquid chromatography analyses of these mutants. A region in the 3' end of crtD which affects bacteriochlorophyll biosynthesis was discovered, and CrtA was found to possess a proline-rich C-terminal region containing a repeated (Ala-Pro)n motif. CrtF also showed a high degree of sequence conservation with eukaryotic O-methyltransferases. This study provides gene sequences and assignments based upon a comprehensive structural, spectroscopic, and biochemical analysis of a range of carotenoid biosynthetic mutants; in each mutation, the point of Tn5 insertion is determined accurate to 1 bp on the gene cluster.
Tumor necrosis factor alpha production as a possible predictor of relapse in patients with multiple sclerosis. (1993)

No biological parameter is currently available as a specific marker of multiple sclerosis (MS) activity. The aim of this study was to determine whether an evolution of the neurological disability is associated with a modified profile of cytokine production. Clinical disease activity was quantitated by the Kurtzke's expanded disability status scale (EDSS). Whole blood was stimulated with phytohemagglutinin (PHA) for 2 hours at 37 degrees C and the activated plasma was assayed for Tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta). Relapsing-remitting MS patients enduring a relapse (RRMS, in relapse) (721 +/- 58 pg/ml, n = 27) and chronic progressive MS (CPMS) patients (516 +/- 33 pg/ml, n = 17) had an higher TNF-alpha production capacity as compared to healthy subjects (143 +/- 25 pg/ml, n = 17), RRMS, stable patients, (123 +/- 11 pg/ml, n = 26) or other neurological diseases (OND) without immunological or inflammatory disease in the peripheral immune compartment (131 +/- 24 pg/ml, n = 14) (t test: p < 0.0001). IL-1 beta production was also significantly higher but to a lesser extent in the same conditions. Concentration of TNF-alpha was also found to be significantly higher in the cerebrospinal fluid (CSF) of CPMS patients (199 +/- 7.8 pg/ml, n = 7, p < 0.0001) but also in RRMS, in relapse (149 +/- 5.7 pg/ml, n = 11, p < 0.05) as compared to RRMS, stable (130 +/- 4.4 pg/ml, n = 7) or OND without inflammatory or immunological disease of the central nervous system (CNS) (142 +/- 6.2 pg/ml, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)
The Treatment of Hypertension in Adult Patients With Diabetes (2002)

Hypertension is an extremely common comorbidity of diabetes, affecting 20–60% of people with diabetes. Hypertension is also a major risk factor for cardiovascular events, such as myocardial infarction and stroke, as well as for microvascular complications, such as retinopathy and nephropathy. Cardiovascular disease is the most costly complication of diabetes and is the cause of 86% of deaths in persons with diabetes (1). However, until recently, little research had been done specifically in patients with diabetes and hypertension. In reviewing the literature on diabetes and hypertension, the authors searched MEDLINE for English language articles using keywords “hypertension,” “diabetes mellitus,” “diabetic nephropathy,” and “coronary artery disease/prevention” starting from 1966. Before 1996, most available data come from secondary analysis from studies done in the general population of people with hypertension, observing a subset with diabetes. Recent studies have demonstrated the effectiveness of blood pressure treatment versus placebo in reducing complications of diabetes (2,3), helped to define the optimal level of blood pressure control (4,5,6), and compared treatment strategies based on different drug classes (7,8,9,10,11,12,13). The results of these studies support an aggressive approach to the diagnosis and treatment of hypertension in patients with diabetes in order to substantially reduce the incidence of both macrovascular and microvascular complications.

### Definition of hypertension in diabetic populations

Epidemiological studies and therapeutic trials have often used different criteria to define hypertension in diabetic patients. Studies in the general population indicate an increased risk of cardiovascular disease with an increase in the level of blood pressure. Thus, an increase in diastolic or systolic blood pressure of 5 mmHg is associated with a concomitant increase in cardiovascular disease of 20–30% (14). Studies in diabetic populations have shown a markedly higher frequency of the progression of diabetic retinopathy …
Angiotensin-converting enzyme and the amyloid precursor protein secretases (1999)

Conference Article| February 01 1999 Angiotensin-converting enzyme and the amyloid precursor protein secretases N. M. Hooper; N. M. Hooper 1 *School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K. 1To whom correspondence should be addressed Search for other works by this author on: This Site PubMed Google Scholar S. Parvathy; S. Parvathy *School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K. Search for other works by this author on: This Site PubMed Google Scholar E. H. Karran; E. H. Karran †Neurosciences Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex CM19 5AW, U.K. Search for other works by this author on: This Site PubMed Google Scholar A. J. Turner A. J. Turner *School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1999) 27 (2): 229–234. https://doi.org/10.1042/bst0270229 Article history Received: August 18 1998 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation N. M. Hooper, S. Parvathy, E. H. Karran, A. J. Turner; Angiotensin-converting enzyme and the amyloid precursor protein secretases. Biochem Soc Trans 1 February 1999; 27 (2): 229–234. doi: https://doi.org/10.1042/bst0270229 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: ACE, angiotensin-converting enzyme, APP, amyloid precursor protein, βA4, β-amyloid peptide, CHO, Chinese hamster ovary, sAPPα, ectodomain of APP released by α-secretase © 1999 Biochemical Society1999 Article PDF first page preview Close Modal You do not currently have access to this content.
Biophysical Techniques for Detection of cAMP and cGMP in Living Cells (2013)

Cyclic nucleotides cAMP and cGMP are ubiquitous second messengers which regulate myriads of functions in virtually all eukaryotic cells. Their intracellular effects are often mediated via discrete subcellular signaling microdomains. In this review, we will discuss state-of-the-art techniques to measure cAMP and cGMP in biological samples with a particular focus on live cell imaging approaches, which allow their detection with high temporal and spatial resolution in living cells and tissues. Finally, we will describe how these techniques can be applied to the analysis of second messenger dynamics in subcellular signaling microdomains.
Staphylococcus aureus protein SAUGI acts as a uracil-DNA glycosylase inhibitor (2013)

DNA mimic proteins are unique factors that control the DNA binding activity of target proteins by directly occupying their DNA binding sites. The extremely divergent amino acid sequences of the DNA mimics make these proteins hard to predict, and although they are likely to be ubiquitous, to date, only a few have been reported and functionally analyzed. Here we used a bioinformatic approach to look for potential DNA mimic proteins among previously reported protein structures. From ∼14 candidates, we selected the Staphylococcus conserved hypothetical protein SSP0047, and used proteomic and structural approaches to show that it is a novel DNA mimic protein. In Staphylococcus aureus, we found that this protein acts as a uracil-DNA glycosylase inhibitor, and therefore named it S. aureus uracil-DNA glycosylase inhibitor (SAUGI). We also determined and analyzed the complex structure of SAUGI and S. aureus uracil-DNA glycosylase (SAUDG). Subsequent BIAcore studies further showed that SAUGI has a high binding affinity to both S. aureus and human UDG. The two uracil-DNA glycosylase inhibitors (UGI and p56) previously known to science were both found in Bacillus phages, and this is the first report of a bacterial DNA mimic that may regulate SAUDG's functional roles in DNA repair and host defense.
Semi-supervised Graph Embedding Approach to Dynamic Link Prediction (2016)

We propose a simple discrete time semi-supervised graph embedding approach to link prediction in dynamic networks. The learned embedding reflects information from both the temporal and cross-sectional network structures, which is performed by defining the loss function as a weighted sum of the supervised loss from past dynamics and the unsupervised loss of predicting the neighborhood context in the current network. Our model is also capable of learning different embeddings for both formation and dissolution dynamics. These key aspects contributes to the predictive performance of our model and we provide experiments with three real--world dynamic networks showing that our method is comparable to state of the art methods in link formation prediction and outperforms state of the art baseline methods in link dissolution prediction.
Tailoring etch directionality in a deep reactive ion etching tool (2000)

Silicon deep reactive ion etching is a process that produces projected two-dimensional shapes due to the inability to control the direction of the energetic ions arriving at the surface of a wafer. The resulting etched profiles present sidewalls which are nominally 90° to the wafer surface. However, we have developed and demonstrated a new technique that allows us to control the angle that trenches make with respect to the wafer surface. This scheme exploits the charging of buried dielectric layers to achieve ion steering and thus control the direction of the etch. The measured angle variation was controlled between −32° and +32° with respect to a line orthogonal to the wafer surface. We report and describe this new technique to control etch angle.
Revising User Profiles: The Search for Interesting Web Sites (1996)

We describe Syskill &amp;amp; Webert, a software agent that learns to rate pages on the World Wide Web (WWW), deciding what pages might interest a user. The user rates explored pages on a three point scale, and Syskill &amp;amp; Webert learns a user profile by analyzing the information on each page. We focus on an extension to Syskill &amp;amp; Webert that lets a user provide the system with an initial profile of his interests in order to increase the classification accuracy without seeing many rated pages. We represent this user profile in a probabilistic way, which allows us to revise the profile as more training data is becoming available using &amp;quot;conjugate priors&amp;quot;, a common technique from Bayesian statistics for probability revision. Unseen pages are classified using a simple Bayesian classifier that uses the revised probabilities. We compare our approach to learning algorithms that do not make use of such background knowledge, and find that a user defined profile can significantly increase the classificati...
Functional expression of the taste‐modifying protein, miraculin, in transgenic lettuce (2006)

Taste-modifying proteins are a natural alternative to artificial sweeteners and flavor enhancers and have been used in some cultures for centuries. The taste-modifying protein, miraculin, has the unusual property of being able to modify a sour taste into a sweet taste. Here, we report the use of a plant expression system for the production of miraculin. A synthetic gene encoding miraculin was placed under the control of constitutive promoters and transferred to lettuce. Expression of this gene in transgenic lettuce resulted in the accumulation of significant amounts of miraculin protein in the leaves. The miraculin expressed in transgenic lettuce possessed sweetness-inducing activity. These results demonstrate that the production of miraculin in edible plants can be a good alternative strategy to enhance the availability of this protein.
THE REACTION OF METHYL 7-OXODEHYDROABIETATE WITH PEBBENZOIC ACID AND THE SYNTHESIS OF 11-METHOXYDEHYDROABIETANE (1972)

Abstract The oxidation of methyl 7-oxodehydroabietate with perbenzoic acid afforded a mixture of lactone (III), quinone (IV), hydroxyester (V), and hydroxyquinone (VI). The intramolecular cyclization of half acid (VIII) derived from V gave two ketoesters (XI and XII). The structures of XI and XII were assigned on the basis of their chemical and spectroscopic studies, and XII was converted into 11-methoxydehydroabietane (XXXIV).
Overlapping TATA-dependent and TATA-independent early promoter activities in the baculovirus gp64 envelope fusion protein gene (1995)

In previous studies to characterize basal and activated transcription from the early promoter of the gp64 envelope fusion protein (efp) gene of the Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus, the TATA box was identified as a functional element, essential for basal transcription from a minimal promoter construct. In the current study, we used discrete deletions and multiple point mutations that removed the functional TATA box from larger promoter constructs of the gp64 efp gene to reveal an overlapping TATA-independent transcriptional activity. TATA-independent transcriptional activity was inhibited in vitro by alpha-amanitin but not by tagetitoxin, demonstrating that like the TATA-dependent activity, the TATA-independent activity is mediated by RNA polymerase II. Using constructs in which the TATA box (TATATAA) was destroyed by substitution mutations, we identified four elements that are required for the TATA-independent activity. Two of the required elements, GATA (at -114) and CACGTG (at -104), were previously shown to specifically bind host transcription factors and activate transcription from the TATA-dependent wild-type gp64 efp promoter. The role of the early start site consensus CAGT sequence in TATA-independent transcription was also examined. Single-nucleotide substitution mutations in the CAGT sequence indicated that certain nucleotides within the CAGT start site were essential. In addition to the start site sequence and two upstream elements, a fourth essential element was identified in the 5' untranslated leader region (5'UTR). While the 5'UTR was not necessary for TATA-dependent transcription, deletion of a 10-bp 5'UTR sequence resulted in the loss of TATA-independent transcriptional activity. Although necessary, neither the GATA, CACGTG, start site region, nor 5'UTR element was alone sufficient for accurately initiated TATA-independent transcription from the consensus CAGT start site. Thus, the gp64 efp early promoter contains overlapping TATA-dependent and TATA-independent transcriptional activities. A number of common sequence elements (GATA, CACGTG, and start site CAGT) are involved in both of these activities, while one element (in the 5'UTR) is required only in the TATA-independent context.
Nanometer-Scale Surface Modification Using the Scanning Probe Microscope:  Progress since 1991 (1997)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNanometer-Scale Surface Modification Using the Scanning Probe Microscope: Progress since 1991R. M. Nyffenegger and R. M. PennerView Author Information Institute for Surface and Interface Science, The Department of Chemistry, University of California, Irvine, Irvine, California 92697-2025 Cite this: Chem. Rev. 1997, 97, 4, 1195–1230Publication Date (Web):June 20, 1997Publication History Received27 September 1996Revised6 February 1997Published online20 June 1997Published inissue 1 June 1997https://pubs.acs.org/doi/10.1021/cr960069ihttps://doi.org/10.1021/cr960069iresearch-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views1917Altmetric-Citations221LEARN 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 SUBJECTS:Deposition,Gold,Layers,Modification,Scanning tunneling microscopy Get e-Alerts