gebhart/patrepeval huggingface dataset:
Nucleotide excision repair gene ERCC1 polymorphisms contribute to cancer susceptibility: a meta-analysis (2011)

Individual studies of the associations between excision repair cross-complimentary group 1 (ERCC1) polymorphisms and cancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship between three well-characterised polymorphisms on ERCC1 and the risk of cancer, we performed a meta-analysis based on 48 publications. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the associations. We found that ERCC1 17677A (rs3212961) variant genotypes were associated with significantly increased overall risk of cancer without substantial heterogeneity (AA versus CC, OR = 1.36, 95% CIs: 1.10-1.68; AC versus CC: OR = 1.11, 95% CIs: 0.99-1.26; dominant comparison: AA/AC versus CC: OR = 1.15, 95% CIs: 1.02-1.29; recessive comparison: AA versus AC/CC: OR = 1.25, 95% CIs: 1.05-1.49). The ERCC1 19007 C (rs11615) allele had null effects on overall risk of cancer; but in the stratified analyses, we observed an elevated association in Asian populations with homozygote variants and hospital-based controls. In addition, during further stratified analyses of cancer groups, homozygote variants were found that are associated with lung cancer and smoking-related cancers. Also, the observed ERCC1 19007 C heterozygote variant contributes to the development of skin cancer. However, the ERCC1 8092C > A (rs3212986) polymorphism did not appear to have an effect on cancer risk. Additionally, no evidence of publication bias was observed in these polymorphisms. Our meta-analysis supports the conclusion that the ERCC1 17677A > C and ERCC1 19007T > C polymorphisms, but not the ERCC1 8092C > A polymorphism, are low-penetrance risk factors for cancer development.
Ketamine: An Update for Its Use in Complex Regional Pain Syndrome and Major Depressive Disorder (2015)

In recent years, there has been significant research in regard to the efficacy of ketamine in regards to treating Complex Regional Pain Syndrome (CRPS) and Major Depressive Disorder (MDD). Many patients have had substantial symptomatic relief; however, not all patients have had positive results. This has prompted current research with evidence to suggest certain biomarkers exist that would infer which patients will/will not respond to ketamine treatment. Current biomarkers of interest include D-Serine (D-Ser) and magnesium, which will be discussed. Whether or not D-Ser and/or magnesium levels should be checked and possibly dictate therapy is an area of future research. It is also possible that downstream metabolites of ketamine are the key to successful therapy.
Algorithms for defining mixed radix FFT flow graphs (1989)

A unified set of algorithms is presented to define the intraconnection and phase rotation structure of flow graphs for arbitrary fast Fourier transforms (FFTs). The same set of basic equations is applied to arbitrary-length FFTs; mixed-radix FFTs; either decimation-in-time or decimation-in-frequency FFTs; and FFTs with ordered inputs, ordered outputs, or both. These equations, which define input and output point indexing of each FFT stage and the twiddle factors used in each stage, are based on forward and backward products of radixes. The same basic products of radixes can be used to represent a wide variety of FFT structures. These equations also permit HOL (high-order language) specification of FFTs for programming signal processors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Concentration of enzymatically active prostate‐specific antigen (PSA) in the extracellular fluid of primary human prostate cancers and human prostate cancer xenograft models (2001)

BACKGROUND Prostate-specific antigen (PSA) targeted prodrugs are under development in our laboratory. Concentrations of total PSA and enzymatically active PSA produced by various human prostate cancer xenograft models have not been well characterized. METHODS The concentration of PSA secreted into the extracellular fluid (ECF) in normal human prostate tissue, primary prostate cancers obtained directly from patients, and serially passageable human prostate cancer xenografts (PC-82, LNCaP, LAPC-4) were determined using Tandem assays. Percent enzymatically active PSA in the ECF and in conditioned media was also determined using a previously validated assay employing a monoclonal antibody to the PSA catalytic site. In addition, the concentration and activity of PSA within sera from men with and without prostate cancer, as well as from tumor-bearing animals, was likewise assayed. RESULTS Normal human prostate tissue and primary human prostate cancers have high concentrations of PSA in the ECF (i.e., 1600–2100 nM). The majority of this PSA is enzymatically active (i.e., 80–90%). Human PC-82 prostate cancer xenografts also have high concentrations of PSA in the ECF (624 ± 360 nM), and the majority of this PSA is also enzymatically active (i.e., 66 ± 4%). In contrast, much lower concentrations of PSA are found in the ECF from LNCaP (45 ± 9 nM) and LAPC-4 (7.3 ± 0.6 nM). Only a small portion of the total PSA isolated from DHT-containing, serum-free, conditioned media from these cell lines is enzymatically active (i.e., ∼18%). While PSA was detected in all serum samples regardless of the type of host, no enzymatically active PSA was detected in any of these serum samples. CONCLUSIONS Prostate cancers obtained directly from patients produce and secrete large amounts of PSA, the majority of which is highly enzymatically active. In contrast, while PSA was detected in the sera, none of this PSA was enzymatically active. This is also the case for the human PC-82 prostate cancer xenografts. In contrast, LNCaP and LAPC-4 human prostate cancer xenograft models secrete ∼70–300-fold less PSA in the ECF than prostate cancers from patients and the majority of this PSA is enzymatically inactive. Also, the serum from these animals had detectable PSA, but none of this PSA was enzymatically active. Thus, these latter two prostate cancer models define the least and the PC-82, the most, optimized xenograft model for screening PSA targeted prodrugs. Prostate 48:1–6, 2001. © 2001 Wiley-Liss, Inc.
[Augmentation of the immune response to islet cell antigens with development of diabetes mellitus caused by interferon-alpha therapy in chronic hepatitis C]. (1999)

We report on a 36-year-old patient suffering from chronic hepatitis C. Because of elevated liver enzymes and histology showing chronic inflammation and periportal fibrosis, interferon-alpha (IFN) therapy was started with a dosage of 5 Mio units three times a week. Four months later the patient hat to be hospitalized due to the typical clinical features of a recent onset type 1 diabetes (BG > 300 mg/dl, HbA1c 9.6%, ketonuria). In serum samples prior to and following interferon therapy, we analyzed titers of diabetes-related autoantibodies responding to GAD65 (glutamic acid decarboxylase), IA2c (tyrosine phosphatase) and ICA (islet cell autoantibodies). While ICA were negative before starting therapy, IA2c-antibodies were highly elevated. In contrast. GAD65-antibodies were elevated only slightly over the cut-off of the assay before therapy (controlled by a second different RIA assay) and increased 100 fold during IFN-alpha treatment. Additionally thyroid antibodies appeared. After the end of the IFN therapy, GAD65- and IA2c antibodies remained on high levels and also ICA could now be found. The patient was positive for HLA-DR4. This case supports the hypothesis that IFN-alpha therapy may lead to an augmented autoimmune reaction against islet cell antigens resulting in the development of diabetes mellitus type 1, especially if there are other predisposing factors before IFN treatment. We further discuss the possible involvement of interferon-alpha in the pathogenesis of autoimmune diabetes with reference to recent studies.
Development of murine hepatic sinusoidal endothelial cells characterized by the expression of hyaluronan receptors (2007)

Endothelial cells (ECs) display distinct structural and functional characteristics depending on the tissue and developmental stage; however, the development of tissue-specific ECs remains poorly understood. Here, we describe the development of hepatic sinusoids in mice based on the expression of hyaluronan receptors Stab2 and Lyve-1. Flk-1(+) cells in and around the liver bud begin to express Stab2 at embryonic day (E) 9.5, before the formation of vascular lumen. Hepatic sinusoidal endothelial cells (HSECs) begin to express Lyve-1 at E10.5, and both markers continue to be expressed in HSECs thereafter. Although HSECs and lymphatic ECs (LECs) are known to share functional and phenotypic characteristics, we clearly show that HSECs can be distinguished from LECs by the expression of molecular markers and higher endocytotic activity. Our results provide new insight into the development of tissue-specific ECs and phenotypic criteria to distinguish HSECs from other types of ECs, including LECs.
Mouse MD-1, a Molecule That Is Physically Associated with RP105 and Positively Regulates Its Expression (1998)

RP105 is a leucine-rich repeat molecule that is expressed on mouse B cells and transmits a growth-promoting signal. An anti-RP105 Ab precipitated additional molecules as well as RP105. These molecules were found to be a mouse homologue of chicken MD-1. Chicken MD-1 was previously isolated as a v-myb-regulated gene, since its transcription increases rapidly after v-myb induction. Mouse MD-1, when transiently expressed as an epitope-tagged protein, is secreted in culture fluid but tethered to the cell surface by coexpressed RP105. An association of these molecules was confirmed by immunoprecipitation with the anti-RP105 Ab and subsequent probing of the epitope tag on MD-1. Moreover, MD-1 has an effect on the expression of RP105. In transient transfection of RP105, the percentage of RP105-positive cells increased more than twice with the coexpression of MD-1. The stable expression of MD-1 conferred approximately a sevenfold increase in cell surface RP105 on a cell line that expresses RP105 alone. Thus, MD-1 is physically associated with RP105 and is important for efficient cell surface expression.
Ca 2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen 1 (1993)

Ca2+ accumulates in the nucleus and DNA undergoes enzymatic cleavage into internucleosome-length fragments before acetaminophen and dimethylnitrosamine produce hepatic necrosis in vivo and toxic cell death in vitro. However, Ca(2+)-endonuclease fragmentation of DNA is characteristic of apoptosis, a type of cell death considered biochemically and functionally distinct from toxic cell death. The present studies investigate DNA fragmentation as a critical event in toxic cell death by testing whether the Ca(2+)-calmodulin antagonist chlorpromazine and the Ca2+ channel blocker verapamil prevent acetaminophen-induced hepatic necrosis by inhibiting Ca2+ deregulation and DNA damage. Acetaminophen overdose in mice produced accumulation of Ca2+ in the nucleus (358% of control) and fragmentation of DNA (250% of control) by 6 h, with peak release of ALT occurring at 12-24 h (38,000 U/l). Pretreatment with chlorpromazine prevented increases in nuclear Ca2+ and DNA fragmentation and nearly abolished biochemical evidence of toxic cell death. Verapamil pretreatment also decreased Ca2+ accumulation and DNA damage while attenuating liver injury. The Ca2+ antagonists did not protect against toxic cell death through hypothermia because neither produced the delay in toxicity that is customarily associated with hypothermia. Nor did chlorpromazine or verapamil protect through inhibiting acetaminophen bioactivation. Chlorpromazine failed to diminish glutathione depletion in whole liver and isolated nuclei. Verapamil (250 microM) also failed to alter glutathione depletion in whole liver and had no effect on acetaminophen-glutathione adduct formation by mouse liver microsomes and by cultured mouse hepatocytes. Collectively, these results support the hypothesis that Ca(2+)-induced DNA fragmentation plays a significant role in cell necrosis produced by acetaminophen and may contribute to toxic cell death caused by other alkylating hepatotoxins.
A 14 ns 256 K*1 CMOS SRAM with multiple test modes (1989)

A methodology to enter and exit from test modes in asynchronous static RAMs (SRAMs) is presented. This chip is fabricated in a 0.7 mu m twin-tub, single-poly, double-metal technology on p/p/sup +/ epitaxial substrate. To prevent hot-electron degradation, a voltage regulator is used in the memory matrix, with the cascoding technique applied in the periphery. Circuits were implemented against voltage bumps and data glitching on the output. A small cell size of 5.1*13.7 mu m/sup 2/ and a chip size of 3.9*9.5 mm/sup 2/ have been achieved.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide (2005)

Endothelial dysfunction (ED) is an early feature of cardiovascular risk and diabetes. Hyperglycemia and hyperlipidemia are causative factors. Excessive endothelial mitochondrial superoxide (ROS) production with hyperglycemia and hyperlipidemia is a key mechanism. Inositol components of an insulin inositol glycan mediator, d-chiro-inositol (DCI) and 3-O-methyl DCI (pinitol), decrease hyperglycemia and hyperlipidemia. We tested whether these, myoinositol and dibutyryl DCI (db-DCI), would prevent or reverse ED in diabetic rats and rabbits. Oral inositols reduced hyperglycemia and hypertriglyceridemia with different potencies and prevented ED in rat aortic rings and mesenteric beds. Inositols added in vitro to five diabetic tissues reversed ED. Relaxation by Ach, NO, and electrical field stimulation was potentiated by inositols in vitro in rabbit penile corpus cavernosa. Inositols in vitro restored impaired contraction by the eNOS inhibitor l-NAME and increased NO effectiveness. DCI and db-DCI decreased elevated ROS in endothelial cells in high glucose and db-DCI reduced PKC activation, hexosamine pathway activity, and advanced glycation end products to basal levels. Xanthine/xanthine oxidase generated superoxide was reduced by superoxide dismutase or inositols, with db-DCI efficacious in a mechanism requiring chelated Fe(3+). Histochemical examination of rat aortic rings for protein SNO demonstrated a decrease in diabetic rings with restoration by inositols. In summary, inositols prevented and reversed ED in rat and rabbit vessels, reduced elevated ROS in endothelial cells, potentiated nitrergic or vasculo-myogenic relaxations, and preserved NO signaling. These effects are related to their metabolic actions, direct superoxide scavenging, and enhancing and protecting NO signaling. Of the inositols tested, db-DCI was most effective.
Absolute quantification of deoxyhaemoglobin concentration in tissue near infrared spectroscopy (1994)

Describes a simple technique for noninvasively determining the absolute concentration of deoxyhaemoglobin (Hb) in living tissue using near infrared spectroscopy (NIRS). The technique uses second-differential spectroscopy to determine the relative concentration of Hb to tissue water by fitting of the spectral features of these two chromophores in the 710 nm to 840 nm region of the near infrared (NIR) spectrum. Since the concentration of tissue water is generally known with accuracies of a few per cent, one can then obtain the absolute concentration of Hb ((Hb)). The validity and likely accuracy of the technique is assessed by applying it to artificially generated NIRS data. Some clinical validation is presented by comparing, during an in vivo study, changes in (Hb) obtained by this method and those calculated using more conventional techniques of relative quantification. Finally, the authors discuss the likely clinical significance of the measurement of (Hb).
Rapid Generation of Stable Transgenic Embryonic Stem Cell Lines Using Modular Lentivectors (2005)

Generation of stable transgenic embryonic stem (ES) cell lines by classic transfection is still a difficult task, requiring time-consuming clonal selection, and hampered by clonal artifacts and gene silencing. Here we describe a novel system that allows construction of lentivectors and generation of stable ES cell lines with > 99% transgene expression within a very short time frame. Rapid insertion of promoters and genes of interest is obtained through a modular recombinational cloning system. Vectors contain central polypurine tract from HIV-1 element and woodchuck hepatitis virus post-transcriptional regulatory element as well as antibiotic resistance to achieve optimal and homogenous transgene expression. We show that the system 1) is functional in mouse and human ES cells, 2) allows the generation of ES cells expressing genes of interest under the control of ubiquitous or tissue-specific promoters, and 3) allows ES cells expressing two constructs through selection with different antibiotics to be obtained. The technology described herein should become a useful tool in stem cell research.
Recommending Learning Algorithms and Their Associated Hyperparameters (2014)

The success of machine learning on a given task dependson, among other things, which learning algorithm is selected and its associated hyperparameters. Selecting an appropriate learning algorithm and setting its hyperparameters for a given data set can be a challenging task, especially for users who are not experts in machine learning. Previous work has examined using meta-features to predict which learning algorithm and hyperparameters should be used. However, choosing a set of meta-features that are predictive of algorithm performance is difficult. Here, we propose to apply collaborative filtering techniques to learning algorithm and hyperparameter selection, and find that doing so avoids determining which meta-features to use and outperforms traditional meta-learning approaches in many cases.
Allium chemistry: simple synthesis of antithrombotic cepaenes from onion and deoxycepaenes from oil of shallot by reaction 1-propenethiolate with sulfonyl halides (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAllium chemistry: simple synthesis of antithrombotic cepaenes from onion and deoxycepaenes from oil of shallot by reaction 1-propenethiolate with sulfonyl halidesEric Block and Shu Hai ZhaoCite this: J. Org. Chem. 1992, 57, 22, 5815–5817Publication Date (Print):October 1, 1992Publication History Published online1 May 2002Published inissue 1 October 1992https://pubs.acs.org/doi/10.1021/jo00048a007https://doi.org/10.1021/jo00048a007research-articleACS PublicationsRequest reuse permissionsArticle Views422Altmetric-Citations20LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Disease‐causing mutations C277R and C277Y modify gating of human ClC‐1 chloride channels in myotonia congenita (2012)

Key points ClC channels are double‐barrelled channels with two ion conduction pathways per individual channel. Substituting cysteine 277 by serine constitutively opens the common gate suggesting that this residue plays a major role in joint openings/closings of both protopores of ClC‐1. We studied here the functional consequences of two novel myotonia‐associated mutations, C277R and C277Y, of human ClC‐1 chloride channels. C277Y not only modified the common gate, but also protopore gating. C277Y inverts the voltage dependence and reduces the open probabilities of protopore and common gates and thus decreases the absolute open probabilities of homodimeric hClC‐1 channels to values below 3%. C277Y reduces single protopore current amplitudes to about two‐thirds of wild‐type values, and inverts the anion permeability sequence. Our results explain the disease‐causing effects and provide novel insights into the molecular processes underlying normal and pathologically altered function of muscle chloride channels. Abstract Myotonia congenita is a genetic condition that is caused by mutations in the muscle chloride channel gene CLCN1 and characterized by delayed muscle relaxation and muscle stiffness. We here investigate the functional consequences of two novel disease‐causing missense mutations, C277R and C277Y, using heterologous expression in HEK293T cells and patch clamp recording. Both mutations reduce macroscopic anion currents in transfected cells. Since hClC‐1 is a double‐barrelled anion channel, this reduction in current amplitude might be caused by altered gating of individual protopores or of joint openings and closing of both protopores. We used non‐stationary noise analysis and single channel recordings to separate the mutants’ effects on individual and common gating processes. We found that C277Y inverts the voltage dependence and reduces the open probabilities of protopore and common gates resulting in decreases of absolute open probabilities of homodimeric channels to values below 3%. In heterodimeric channels, C277R and C277Y also reduce open probabilities and shift the common gate activation curve towards positive potentials. Moreover, C277Y modifies pore properties of hClC‐1. It reduces single protopore current amplitudes to about two‐thirds of wild‐type values, and inverts the anion permeability sequence to I − = NO 3 − &gt; Br − &gt; Cl − . Our findings predict a dramatic reduction of the muscle fibre resting chloride conductance and thus fully explain the disease‐causing effects of mutations C277R and C277Y. Moreover, they provide additional insights into the function of C277, a residue recently implicated in common gating of ClC channels.
A Click Approach to Unprotected Glycodendrimers (2006)

Click chemistry in combination with ultrafiltration has allowed the quick, efficient, and reliable multivalent conjugation of unprotected alkyne-derived carbohydrates to three generations of azido-terminated gallic acid−triethylene glycol dendrimers under aqueous conditions. The reported procedure allows the atom economical incorporation of up to 27 unprotected fucose, mannose, and lactose residues, in reproducible high yields (up to 92%), requiring only catalytic amounts of Cu. The completion of the conjugation process was clearly established in all cases by both 1H NMR and MALDI-TOF MS.