gebhart/patrepeval huggingface dataset:
Risk- and non-risk-associated variants at the 10q26 AMD locus influence ARMS2 mRNA expression but exclude pathogenic effects due to protein deficiency (2011)

Fifteen variants in 10q26 are in strong linkage disequilibrium and are associated with an increased risk for age-related macular degeneration (AMD), a frequent cause of blindness in developed countries. These variants tag a single-risk haplotype encompassing the genes ARMS2 (age-related maculopathy susceptibility 2) and part of HTRA1 (HtrA serine peptidase 1). To define the true AMD susceptibility gene in 10q26, several studies have focused on the influence of risk alleles on the expression of ARMS2 and/or HTRA1, but the results have been inconsistent. By heterologous expression of genomic ARMS2 variants, we now show that ARMS2 mRNA levels transcribed from the risk haplotype are significantly reduced compared with non-risk mRNA isoforms. Analyzing variant ARMS2 constructs, this effect could specifically be assigned to the known insertion/deletion polymorphism (c.(*)372_815del443ins54) in the 3'-untranslated region of ARMS2. Reporter gene assays with HTRA1 promoter sequences demonstrated the presence of a Müller glia-specific cis-regulatory region further upstream of the transcription start site. However, AMD risk alleles had little or no effect on HTRA1 promoter activity in the retina. Analysis of a large series of human post-mortem retina/retinal pigment epithelial samples heterozygous for the risk haplotype confirmed the in vitro/ex vivo results and demonstrated that the risk haplotype affects ARMS2 but not HTRA1 mRNA expression. Furthermore, we provide in vivo evidence that a common non-risk-associated non-synonymous variant (rs2736911) also leads to decreased ARMS2 transcript levels. Consequently, our data suggest that pathogenic effects due to ARMS2 protein deficiency are unlikely to account for AMD pathology.
CRUNCHING DATA WITH CLUSTERS (2000)

RETURN TO ISSUEPREVNewsNEXTCRUNCHING DATA WITH CLUSTERSLow-cost Beowulf-class computer systems can perform as well as supercomputersELIZABETH K. WILSONView Author Information C&EN West Coast News BureauCite this: Chem. Eng. News 2000, 78, 2, 27Publication Date (Print):January 10, 2000Publication History Published online12 November 2010Published inissue 10 January 2000https://pubs.acs.org/doi/10.1021/cen-v078n002.p027https://doi.org/10.1021/cen-v078n002.p027newsACS PublicationsCopyright © 2000 American Chemical SocietyArticle Views13Altmetric-Citations-LEARN 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 options SUBJECTS:Cluster chemistry Get e-Alerts
Mice expressing aberrant sperm-specific protein PMIS2 produce normal-looking but fertilization-incompetent spermatozoa (2012)

Eight kinds of gene-disrupted mice (Clgn, Calr3, Pdilt, Tpst2, Ace, Adam1a, Adam2, and Adam3) show impaired sperm transition into the oviducts and defective sperm binding to the zona pellucida. All of these knockout strains are reported to lack or show aberrant expression of a disintegrin and metallopeptidase domain 3 (ADAM3) on the sperm membrane. We performed proteomic analyses of the proteins of these infertile spermatozoa to clarify whether the abnormal function is caused exclusively by a deficiency in ADAM3 expression. Two proteins, named PMIS1 and PMIS2, were missing in spermatozoa from Clgn-disrupted mice. To study their roles, we generated two gene-disrupted mouse lines. Pmis1-knockout mice were fertile, but Pmis2-knockout males were sterile because of a failure of sperm transport into the oviducts. Pmis2-deficient spermatozoa also failed to bind to the zona pellucida. However, they showed normal fertilizing ability when eggs surrounded with cumulus cells were used for in vitro fertilization. Further analysis revealed that these spermatozoa lacked the ADAM3 protein, but the amount of PMIS2 was also severely reduced in Adam3-deficient spermatozoa. These results suggest that PMIS2 might function both as the ultimate factor regulating sperm transport into the oviducts and in modulating sperm-zona binding.
On the PAR Reduction of OFDM Signals Using Multiple Signal Representation (2004)

Multiple signal representation (MSR) techniques have been used to reduce the high peak-to-average power ratios (PAR) of orthogonal frequency division multiplexing (OFDM) signals. These includes partial transmit sequences (PTS), selected mapping (SLM), selective scrambling and interleaving. All MSR techniques often improve the PAR statistics and are iterative in nature. The PAR reduction obtainable depends on the number of iterations performed, which also increases the complexity of the OFDM transmitter. However, a means to estimate the achievable PAR reduction for a given number of iterations has not been reported in the literature so far. This paper derives a lower bound on the achievable PAR when a MSR technique with a given complexity is used. Our analytical results show a clear asymptotic behavior of the PAR as the number of iterations is increased. Simulation results justify the significance and accuracy of the PAR bound derived.
Conformational analysis of synthetic heparin‐like oligosaccharides containing α‐L‐idopyranosyluronic acid (1987)

Abstract High‐field NMR spectroscopy of synthetic heparin‐like di‐ and trisaccharides has afforded a complete set of inter‐proton‐coupling data on α‐L‐idopyranosyluronic acid, which have been used for conformational analysis. These data lead to the conclusion that α‐L‐iduronic acid may display considerable conformational freedom including 1 C 4 , 4 C 1 and 2 S 0 (e.g. compound 1 ) conformers. The 2‐ O ‐sulphate substituent at iduronic acid tends to stabilize the 1 C 4 conformation ( e.g. compounds 2 and 4 ). In addition carbohydrate substituents at position 4 hinder the 4 C 1 conformation ( e.g. compound 3a,b versus 1 ). Furthermore, the conformation of α‐L‐idopyranosyluronic acid 2‐sulphate is affected seriously by the substituent at position 2 of the non‐reducing glucosamine residue. Thus the presence of an ammonium group ( i.e. compound 7 ) leads to unexpected deformation of the 1 C 4 form of iduronic acid, whereas a sulphamino substituent at this position ( e.g. compound 5a,b ) brings about the 2 S 0 skew boat conformation. The iduronic acid moiety of a trisaccharide (compound 6 ), which represents a part of the anti‐thrombin III‐binding site of heparin, shows conformational preference for the 2 S 0 form in aqueous solution under low ionic conditions. However, increasing the ionic strength ( e.g. 3 M NaCl) causes the conformational equilibrium to incline towards the 1 C 4 chair conformer. This feature may be indicative for the mechanism of conformational control as exerted by the AT‐III protein upon heparin binding. Several molecular models of preferred conformers have been constructed; Nuclear Overhauser Enhancement data, exo‐anomeric effect and Van der Waals interactions have been taken into account.
DOK3 Negatively Regulates LPS Responses and Endotoxin Tolerance (2012)

Innate immune activation via Toll-like receptors (TLRs), although critical for host defense against infection, must be regulated to prevent sustained cell activation that can lead to cell death. Cells repeatedly stimulated with lipopolysaccharide (LPS) develop endotoxin tolerance making the cells hypo-responsive to additional TLR stimulation. We show here that DOK3 is a negative regulator of TLR signaling by limiting LPS-induced ERK activation and cytokine responses in macrophages. LPS induces ubiquitin-mediated degradation of DOK3 leading to SOS1 degradation and inhibition of ERK activation. DOK3 mice are hypersensitive to sublethal doses of LPS and have altered cytokine responses in vivo. During endotoxin tolerance, DOK3 expression remains stable, and it negatively regulates the expression of SHIP1, IRAK-M, SOCS1, and SOS1. As such, DOK3-deficient macrophages are more sensitive to LPS-induced tolerance becoming tolerant at lower levels of LPS than wild type cells. Taken together, the absence of DOK3 increases LPS signaling, contributing to LPS-induced tolerance. Thus, DOK3 plays a role in TLR signaling during both naïve and endotoxin-induced tolerant conditions.
A mew computer method for the storage and manipulation of DNA gel reading data (1980)

This paper describes a new way of storing DNA gel reading data and an accompanying set of computer programs. These programs will perform all the manipulations that are required on data gained by the so-called 'shotgun' method of DNA sequencing. This system simplifies the computer processing involved with this sequencing method and also has the capability of being able at any time during a project to display, lined up in register, all the gel reading covering any section of the sequence.
CapacitationIn Vitroof Stallion Spermatozoa: Comparison of Progesterone‐Induced Acrosome Reactions in Fertile and Subfertile Males (1995)

Mammalian sperm that have completed capacitation are capable of undergoing the acrosome reaction in response to a number of biological and chemical stimuli. In the present report, we have investigated the ability of progesterone to stimulate acrosome reactions of stallion sperm capacitated in vitro. Motile sperm were selected by a two-layer Percoll gradient centrifugation and were incubated in TALP medium modified by the 1:1 (v/v) addition of TEST-yolk medium for 5 hours at 39 degrees C, under 5% CO2 in humidified air. Sperm incubated in vitro in TALP-TEST medium had a higher percentage of acrosome reactions following the addition of progesterone (3.18 mumol/L) compared to controls (P < 0.05). Furthermore, sperm from stallions classified as fertile on the basis of breeding history had higher percentages of progesterone-induced acrosome reactions in comparison with stallions classified as subfertile (P < 0.05). Acrosome reactions were assessed routinely by fluoresceinated lectin binding, but the physiological appearance of induced acrosome reactions was confirmed at the ultrastructural level by transmission electron microscopy. We conclude that 1) TALP-TEST medium supports stallion sperm capacitation in vitro, 2) progesterone-induced acrosome reactions are physiological, and 3) sperm from fertile stallions may be more responsive to progesterone-induced acrosome reactions than those of subfertile stallions. This is the first report in a nonhuman species that differences exist between the sperm of fertile and subfertile males in the ability to capacitate and acrosome react in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Antihyperglycemic activity of novel substituted 3H-1,2,3,5-oxathiadiazole 2-oxides (1992)

A series of substituted 3H-1,2,3,5-oxathiadiazole-2-oxides (6) was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. The oxathiadiazoles 6 were synthesized by a two-step sequence: treatment of a substituted acetonitrile (4) with hydroxylamine to give the corresponding amidoxime (5) and cyclization with thionyl chloride to yield 6. In terms of potency, the 2-naphthalenylmethyl group (as in compound 3) was found to be the optimal substituent in this series. Compound 3 was approximately 5 times more potent than ciglitazone (1).
Structure and Regulation of the Leukocyte Adhesion Receptor LFA-1 and Its Counterreceptors, ICAM-1 and ICAM-2 (1989)

Immune responses hinge on appropriate interactions between T lymphocytes and antigen-presenting cells (APC) or target cells. Although immunological specificity is mediated by antigen receptors (Bjorkman et al. 1987), antigen-specific cytotoxicity and helper-T-lymphocyte responses require lymphocyte function associated-1 (LFA-1) and other "accessory molecules" (Springer et al. 1987). LFA-1 mediates adhesion between lymphocytes and other cells and, in the process, may inform the cell of its environment via signal transduction mechanisms (Springer et al. 1987; van Noesel et al. 1988), as do other integrins (Menko and Boettinger 1987). Therefore, we will refer to LFA-1 as an adhesion receptor. LFA-1 mediates adhesion by binding to cell-surface molecules on other cells that include ICAM-1 and ICAM-2 (Marlin and Springer 1987; Makgoba et al. 1988b; Staunton et al. 1989a). We will refer to these ligand molecules as counterreceptors, based on the idea that they may also be capable of transducing signals.
Molecular cytogenetic analysis of a nontumorigenic human breast epithelial cell line that eventually turns tumorigenic: Validation of an analytical approach combining karyotyping, comparative genomic hybridization, chromosome painting, and single‐locus fluorescence in situ hybridization (1997)

The immortalized, nontumorigenic human breast epithelial cell line HMT-3522 has been used as a model for premalignant and, eventually, malignant development. During cultivation, the karyotype evolution was followed. At an early stage, a very long constant phase showed a near-diploid karyotype, with only five marker chromosomes. DNA from this phase was used for comparative genomic hybridization (CGH) analysis, confirming a previously known MYC amplification, and the integration sites were subsequently determined by single-locus fluorescence in situ hybridization (FISH). Furthermore, gains of 5q22-qter and 20q11-qter and deletion of most of chromosome 6 (6p23-qter) were detected by CGH. Because of uncertainty about some of the indicated changes, including a deletion of 1p35-pter, the CGH findings were investigated more closely by chromosome painting, leading to a revision of the karyotype: 45,XX,del(1)(p35),−6,dup(8)(pter→qter::qter→q24),der(12) t(6;12)(p23;p13),der(14)t(5;14)(q22;q32.3),der(17)t(8;17;20)(17pter→17q25::8qter→8q23::8q24→8qter::8q24→8qter::8q23→8q24.1::20q11→20qter). Some karyotypic changes were confirmed by CGH; others had to be revised; and, in the 1p35 region, classical cytogenetics seems superior to CGH. However, CGH revealed a karyotypically unsuspected dup(20q) that might be of special relevance to breast tumor initiation or progression. Our study confirms that CGH is supplementary to current technologies, e.g., karyotyping and Southern analysis, but cannot replace them. In addition, our cell line turned out to be an excellent model for comparison among the different methods. The results imply that future cytogenetic analyses of complex karyotypes should be based on a combination of karyotyping, CGH, and FISH. Genes Chromosom. Cancer 20:30–37, 1997. © 1997 Wiley-Liss, Inc.
Potential strategies utilised by papillomavirus to evade host immunity (1999)

The co-evolution of papillomaviruses (PV) and their mammalian hosts has produced mechanisms by which PV might avoid specific and non-specific host immune responses. Low level expression of PV proteins in infected basal epithelial cells, together with an absence of inflammation and of virus-induced cell lysis, restricts the opportunity for effective PV protein presentation to immunocytes by dendritic cells. Additionally, PV early proteins, by a range of mechanisms, may restrict the efficacy of antigen presentation by these cells. Should an immune response be induced to PV antigens, resting keratinocytes (KC) appear resistant to interferon-gamma-enhanced mechanisms of cytotoxic T-lymphocyte (CTL)-mediated lysis, and expression of PV antigens by resting KC can tolerise PV-specific CTL. Thus, KC, in the absence of inflammation, may represent an immunologically privileged site for PV infection. Together, these mechanisms play a part in allowing persistence of PV-induced proliferative skin lesions for months to years, even in immunocompetent hosts.
Readily-Extracted Proteins from Merino Wool (1982)

Treatments of wool with either formic acid or 50% aqueous propanol are known to increase abrasion resistance. The proteins extracted by these treatments have been characterized by amino acid analysis and polyacrylamide gel electrophoresis in urea at pH 2.6 and 8.9, and in sodium dodecyl sulfate (SDS). SDS electrophoretic mobilities of the proteins indicated that they have molecular weights below 10,000. The proteins solubilized by propanol contained large amounts of glycine, the aromatic amino acids (tyrosine and phenylalanine), and serine, and a moderate amount of half-cystine. They are shown to be Type I high-tyrosine proteins, possibly derived from the matrix of the cortex. On the other hand, the fraction extracted with formic acid contained virtually no half-cystine and a large amount of glutamic acid, as well as glycine, serine, and the aromatic amino acids, and possibly originated in the cell membrane complex.
The Sec-independent Twin-arginine Translocation System Can Transport Both Tightly Folded and Malfolded Proteins across the Thylakoid Membrane (1998)

A subset of lumen proteins is transported across the thylakoid membrane by a Sec-independent translocase that recognizes a twin-arginine motif in the targeting signal. A related system operates in bacteria, apparently for the export of redox cofactor-containing proteins. In this report we describe a key feature of this system, the ability to transport folded proteins. The thylakoidal system is able to transport dihydrofolate reductase (DHFR) when an appropriate signal is attached, and the transport efficiency is almost undiminished by the binding of folate analogs such as methotrexate that cause the protein to fold very tightly. The system is moreover able to transport DHFR into the lumen with methotrexate bound in the active site, demonstrating that the DeltapH-driven transport of large, native structures is possible by this pathway. However, correct folding is not a prerequisite for transport. Truncated, malfolded DHFR can be translocated by this system, as can physiological substrates that are severely malfolded by the incorporation of amino acid analogs.
Synthesis of lin-benzoinosine, lin-benzoxanthosine, and lin-benzoguanosine (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of lin-benzoinosine, lin-benzoxanthosine, and lin-benzoguanosineGene E. Keyser and Nelson J. LeonardCite this: J. Org. Chem. 1979, 44, 17, 2989–2994Publication Date (Print):August 1, 1979Publication History Published online1 May 2002Published inissue 1 August 1979https://pubs.acs.org/doi/10.1021/jo01331a008https://doi.org/10.1021/jo01331a008research-articleACS PublicationsRequest reuse permissionsArticle Views157Altmetric-Citations10LEARN 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
Moderate mutation rate in the SARS coronavirus genome and its implications (2004)

The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic.
Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma (2013)

In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal adenocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag single-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpathways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations.
Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction. (1993)

Interleukin-6 (IL-6) is a multifunctional cytokine that is proving to be a major contributor to the acute phase inflammatory response. IL-6 expression is normally low and serum levels are usually nondetectable in the absence of inflammation. With advancing age, however, serum levels become detectable and it is proposed that this reflects an age-associated loss in the normal regulation of gene expression for this molecule. There is also speculation that IL-6 may contribute to the pathogenesis of several diseases that are common in late-life including lymphoma, osteoporosis, and Alzheimer's disease. In this report we demonstrate that plasma levels of IL-6 rise with advancing age in well-selected healthy elderly people and comparably in old rhesus monkeys. That this change reflects a primary aging process is suggested by our findings in C57BL/6 mice in which the age-associated increase in the in vitro synthesis of IL-6 is largely prevented by life span-extending dietary restriction.