gebhart/patrepeval huggingface dataset:
Design and synthesis of a 3′- O -allyl photocleavable fluorescent nucleotide as a reversible terminator for DNA sequencing by synthesis (2005)

DNA sequencing by synthesis (SBS) offers an approach for potential high-throughput sequencing applications. In this method, the ability of an incoming nucleotide to act as a reversible terminator for a DNA polymerase reaction is an important requirement to unambiguously determine the identity of the incorporated nucleotide before the next nucleotide is added. A free 3'-OH group on the terminal nucleotide of the primer is necessary for the DNA polymerase to incorporate an incoming nucleotide. Therefore, if the 3'-OH group of an incoming nucleotide is capped by a chemical moiety, it will cause the polymerase reaction to terminate after the nucleotide is incorporated into the DNA strand. If the capping group is subsequently removed to generate a free 3'-OH, the polymerase reaction will reinitialize. We report here the design and synthesis of a 3'-modified photocleavable fluorescent nucleotide, 3'-O-allyl-dUTP-PC-Bodipy-FL-510 (PC-Bodipy, photocleavable 4,4-difluoro-4-bora-3alpha,4alpha-diaza-s-indacene), as a reversible terminator for SBS. This nucleotide analogue contains an allyl moiety capping the 3'-OH group and a fluorophore Bodipy-FL-510 linked to the 5 position of the uracil through a photocleavable 2-nitrobenzyl linker. Here, we have shown that this nucleotide is a good substrate for a DNA polymerase. After the nucleotide was successfully incorporated into a growing DNA strand and the fluorophore was photocleaved, the allyl group was removed by using a Pd-catalyzed reaction to reinitiate the polymerase reaction, thereby establishing the feasibility of using such nucleotide analogues as reversible terminators for SBS.
Nowcasting is not Just Contemporaneous Forecasting (2009)

We consider the reasons for nowcasting, the timing of information and sources thereof, especially contemporaneous data, which introduce different aspects compared to forecasting. We allow for the impact of location shifts inducing nowcast failure and nowcasting during breaks, probably with measurement errors. We also apply a variant of the nowcasting strategy proposed in Castle and Hendry (2009) to nowcast Euro Area GDP growth. Models of disaggregate monthly indicators are built by automatic methods, forecasting all variables that are released with a publication lag each period, then testing for shifts in available measures including survey data, switching to robust forecasts of missing series when breaks are detected.
Crystallization of amorphous silicon by reconstructive transformation utilizing gold (1991)

A gold layer one order of magnitude thinner than the thickness of an amorphous silicon layer in intimate contact leads to the dissolution of the amorphous silicon into the liquid and the subsequent precipitation of crystalline Si as the liquid phase propagates into the amorphous phase at above eutectic temperatures. The crystalline Si precipitate has grain sizes of the order of 6 μm. The Si/Au liquid is very sensitive to constitutional supercooling and subsequent crystallization.
Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney (2006)

The mechanisms involved in renal ischemia-reperfusion injury (IRI) are complex and appear to involve the early participation of bone marrow-derived cells. T lymphocytes participate in the pathogenesis of IRI. Sphingosine 1-phosphate (S1P) induces peripheral T cell depletion. Therefore, we hypothesized that S1P1 receptor activation protects kidney from IRI. FTY-720, a non-receptor-selective sphingosine analog, was given intraperitoneally to C57BL/6 mice, and animals were subjected to ischemia for 32 min followed by reperfusion for 24 h. Plasma creatinine, blood count, myeloperoxidase (MPO) activity, and renal histology were determined. IRI led to a marked increase in plasma creatinine, MPO activity, leukocyte infiltration, and vascular permeability. FTY-720 significantly decreased plasma creatinine in a dose-response manner with a maximal reduction of approximately 73 and approximately 69% with doses of 240 and 48 microg/kg, respectively. MPO, leukocyte infiltration, vascular permeability, and peripheral blood lymphocyte counts were markedly decreased with FTY-720 treatment. The protective effect of FTY-720 was reversed with VPC-44116, a selective S1P1 receptor antagonist. Furthermore, SEW-2871, a selective S1P1 agonist, significantly decreased plasma creatinine in a dose-response manner with a maximal reduction of approximately 70% with a dose of 10 mg/kg. Analysis of kidneys by light microscopy revealed minimal histological signs of ischemic injury with FTY-720 or SEW-2871 treatment compared with the vehicle group. Using RT-PCR, we found a time-dependent increase in the S1P1 mRNA expression following IRI that begins after 2 h with the maximum expression at approximately 4 h. We conclude that the protective effect of FTY-720 is due primarily to activation of S1P1 receptors. The mechanism of protection is not known but may be related to peripheral lymphocyte depletion or direct effects on kidney cells expressing S1P1 receptor.
SIRT1 Protects against Microglia-dependent Amyloid-β Toxicity through Inhibiting NF-κB Signaling (2005)

Accumulating evidence suggests that neurodegeneration induced by pathogenic proteins depends on contributions from surrounding glia. Here we demonstrate that NF-kappaB signaling in microglia is critically involved in neuronal death induced by amyloid-beta (Abeta) peptides, which are widely presumed to cause Alzheimer disease. Constitutive inhibition of NF-kappaB signaling in microglia by expression of the nondegradable IkappaBalpha superrepressor blocked neurotoxicity, indicating a pivotal role for microglial NF-kappaB signaling in mediating Abeta toxicity. Stimulation of microglia with Abeta increased acetylation of RelA/p65 at lysine 310, which regulates the NF-kappaB pathway. Overexpression of SIRT1 deacetylase and the addition of the SIRT1 agonist resveratrol markedly reduced NF-kappaB signaling stimulated by Abeta and had strong neuroprotective effects. Our results support a glial loop hypothesis by demonstrating a critical role for microglial NF-kappaB signaling in Abeta-dependent neurodegeneration. They also implicate SIRT1 in this pathway and highlight the therapeutic potential of resveratrol and other sirtuin-activating compounds in Alzheimer disease.
Selective androgen receptor modulators for frailty and osteoporosis. (2007)

Androgens play an important role not only in male sexual differentiation, puberty, sexual behavior and spermatogenesis, but also in the maintenance of bone architecture and muscle mass and strength. For decades, steroidal androgens have been used by hypogonadal and aging men as hormone replacement therapy, and abused by prominent athletes as anabolic agents for enhancing physical performance. The use of steroidal androgens is associated with hepatotoxicity, potential for prostate stimulation, virilizing actions and other side effects resulting from their cross-reactivity to related steroid receptors. Therefore, to utilize the therapeutic potential of the androgen receptor for the treatment of indications such as osteoporosis and frailty, several pharmaceutical and biotechnology companies are developing non-steroidal tissue-selective androgen receptor modulators (SARMs) that retain the beneficial properties of natural androgens and exhibit better therapeutic indices. This article reviews the mechanism of androgen action, novel non-steroidal ligands under development and future directions of SARM research for the discovery of novel modulators for frailty and osteoporosis.
Integrative Recombination of Bacteriophage : In Vitro Study of the Intermolecular Reaction (1979)

The integrative recombination of bacteriophage λ is the best-characterized recombination reaction known. The reaction has been extensively studied through genetic analysis (Gottesman and Weisberg 1971; Weisberg et al. 1977). More recently, an in vitro system has been developed and used to obtain further biochemical and molecular biological information which was difficult to obtain through in vivo studies (Nash, 1977). We now also know the structure of the sites on DNA involved in the reaction (attachment sites; attP is the attachment site on the phage genome and attB is that on the host bacterial chromosome) down to the level of base sequence (Landy and Ross 1977).
A linear time algorithm for optimal routing around a rectangle (1988)

The problem of connecting a set of terminals that lie on the sides of a rectangle to minimize the total area is discussed. An O ( n ) algorithm is presented to solve this problem when the set of n terminals is initially sorted. The strategy in this paper is to reduce the problem to several problems such that no matter what instance is started with, at least one of these problems can be solved optimally by a greedy method.
ReBISR: A Reconfigurable Built-In Self-Repair Scheme for Random Access Memories in SOCs (2009)

Built-in self-repair (BISR) technique has been widely used to repair embedded random access memories (RAMs). This paper presents a reconfigurable BISR (ReBISR) scheme for repairing RAMs with different sizes and redundancy organizations. An efficient redundancy analysis algorithm is proposed to allocate redundancies of defective RAMs. In the ReBISR, a reconfigurable built-in redundancy analysis (ReBIRA) circuit is designed to perform the redundancy algorithm for various RAMs. Also, an adaptively reconfigurable fusing methodology is proposed to reduce the repair setup time when the RAMs are operated in normal mode. Experimental results show that the ReBISR scheme can achieve high repair rate (i.e., the ratio of the number of repaired RAMs to the number of defective RAMs). The area cost of the ReBISR is very small, which is only about 2.7% for four RAMs (one 4 Kbit RAM, one 16 Kbit RAM, one 128 Kbit RAM, and one 512 Kbit RAM). Moreover, the time overhead of redundancy analysis is very small. For example, the ratio of the redundancy analysis time to the test time for a 512 Kbit RAM tested by a March-14 test with solid data backgrounds is only about 0.25%. On the other hand, the proposed fusing scheme can achieve about 86.94% reduction of repair setup time in comparison with a typical fusing scheme for 20 512 × 16 × 64-bit RAMs of which each RAM has one spare row and one spare column.
Insecticidal Properties of Several Monoterpenoids to the House Fly (Diptera: Muscidae), Red Flour Beetle (Coleoptera: Tenebrionidae), and Southern Corn Rootworm (Coleoptera: Chrysomelidae) (1994)

House flies, Musca domestica (L.), and their eggs were treated with 22 monoterpenoids to determine the topical, fumigant, and ovicidal activity of each compound. Fumigant activity of 14 monoterpenoids were examined further using red flour beetles, Tribolium castaneum (Herbst). Third-instar southern corn rootworm, Diabrotica undecimpunctata howardi Barber, were treated with carvacrol, citral, citronellal, menthol, pulegone, verbenol, and verbenone to determine their activity on larvae. Structure-activity relationships were evaluated with the toxicity data. We made comparisons between monocyclic aromatic, acyclic aliphatic, monocyclic aliphatic, and bicyclic aliphatic alcohols, ketones, aldehydes, and acids to determine toxicity differences involving the skeletal structure, amount of saturation, and associated functional groups of monoterapenoids. Ketones were more effective than alcohols in the topical, fumigant (T. castaneum), and ovicidal bioassays and less toxic than an analogous aldehyde in the topical, fumigant (M. domestica), and ovicidal bioassays. Aldehydes were more toxic than alcohols in the topical and fumigant (M. domestica) bioassays. In the topical and ovicidal bioassays, aromatic or acyclic alcohols, or both, were more effective than monocyclic and bicyclic alcohols. Vapors of bicyclic ketones were more toxic than monocyclic ketones to adult M. domestica. Monoterpenoid alcohols containing three carbon-carbon double bonds were more effective than saturated alcohols in the topical and larval bioassays. A mono-unsaturated ketone was more toxic than a structurally similar saturated ketone and two di-unsaturated ketones when it was applied topically to adult M. domestica. A saturated monocyclic ketone inhibited egg hatch more effectively than unsaturated monocyclic ketones.
Microelectrofluidic Systems: Modeling and Simulation (2002)

INTRODUCTION Modeling and Simulation Issues Modeling and Simulation Needs Overview HIERARCHICAL MODELING MEFS Dynamic Modeling and Simulation at Circuit Level MEFS System-Level Modeling and Simulation Conclusion SYSTEMC-BASED HIERARCHICAL DESIGN ENVIRONMENT Suitability of Modeling Languages for Hierarchical Design Building Design Environment with SystemC Conclusion SYSTEM-LEVEL SIMULATION AND PERFORMANCE EVALUATION MEFS Computing and Architecture Hierarchical Modeling and Simulation Methodology Micro-Chemical Handling System System Performance Analysis and Design Optimization Conclusion CIRCUIT-LEVEL OPTIMIZATION Simulation Design Methodology Optimization Verification On-Target Design Optimization Robust Design Optimization Application Flexibility Optimization Conclusion PERFORMANCE EVALUATION Introduction Continuous-Flow PCR System Droplet-Based PCR System Comparison Between Continuous-Flow PCR and Droplet PCR Scheduling of Microfluidic Operations for Reconfigurable Two-Dimensional Electrowetting Arrays CONCLUSION APPENDICES VHDL Queuing Model Hierarchical Environment with SystemC Keywords: Nanoscience, Nanotechnology
Measuring the sensations of urge and bladder filling during cystometry in urge incontinence and the effects of neuromodulation (2002)

A new patient operated key-pad device provided a reliably objective measure of sensations of urge during urodynamics without the need for prompting. Neuromodulation using noninvasive pudendal afferent stimulation suppressed these sensations whilst increasing bladder volume.
Toward Early Safety Alert Endpoints: Exploring Biomarkers Suggestive of Microbicide Failure (2013)

Several microbicides, including nonoxynol-9 (N-9) and cellulose sulfate (CS), looked promising during early trials but failed in efficacy trials. We aimed to identify Phase I mucosal safety endpoints that might explain that failure. In a blinded, randomized, parallel trial, 60 healthy premenopausal sexually abstinent women applied Universal HEC placebo, 6% CS or 4% N-9 gel twice daily for 13½ days. Endpoints included immune biomarkers in cervicovaginal lavage (CVL) and endocervical cytobrushes, inflammatory infiltrates in vaginal biopsies, epithelial integrity by naked eye, colposcopy, and histology, CVL anti-HIV activity, vaginal microflora, pH, and adverse events. Twenty women enrolled per group. Soluble/cellular markers were similar with CS and placebo, except secretory leukocyte protease inhibitor (SLPI) levels decreased in CVL, and CD3(+) and CD45(+) cells increased in biopsies after CS use. Increases in interleukin (IL)-8, IL-1, IL-1RA, and myeloperoxidase (MPO) and decreases in SLPI were significant with N-9. CVL anti-HIV activity was significantly higher during CS use compared to N-9 or placebo. CS users tended to have a higher prevalence of intermediate Nugent score, Escherichia coli, and Enterococcus and fewer gram-negative rods. Most Nugent scores diagnostic for bacterial vaginosis were in N-9 users. All cases of histological inflammation or deep epithelial disruption occurred in N-9 users. While the surfactant N-9 showed obvious biochemical and histological signs of inflammation, more subtle changes, including depression of SLPI, tissue influx of CD45(+) and CD3(+) cells, and subclinical microflora shifts were associated with CS use and may help to explain the clinical failure of nonsurfactant microbicides.
TRANSFORMATION IN YEAST: DEVELOPMENT OF A HYBRID CLON- ING VECTOR AND ISOLATION OF THE CAN! GENE (Saccharomyces cerevisiae, plasmid vector; arginine permease) (1979)

SUMMARY We have constructed a plasmid, YEpl3, which when used in conjunction with transformation in yeast is a suitable vector for isolating specific yeast genes. The plasmid consists of pBR322, the LEU2 gene of yeast, and a DNA fragment containing a yeast origin of replication from 2/~ circle. We have demonstrated the utility of this cloning system by isolating the yeast gene encoding the arginine permease, CAN1, from a pool of random yeast DNA fragments inserted into YEpl3.
Glioblastoma multiforme: The terminator (2000)

Glioblastoma multiforme is the most aggressive of the gliomas, a collection of tumors arising from glia or their precursors within the central nervous system. Clinically, gliomas are divided into four grades; unfortunately, the most aggressive of these, grade 4 or glioblastoma multiforme (GBM), is also the most common in humans. Because most patients with GBMs die of their disease in less than a year and essentially none has long-term survival, these tumors have drawn significant attention; however, they have evaded increasingly cleaver and intricate attempts at therapy over the last half-century. The paper by Gromeier et al. (1) in this issue of PNAS is the newest chapter in this saga, describing a hybrid virus that infects and kills clonal human glioma cell lines, in culture and implanted in athymic mice, without affecting nonneoplastic cells within the brain. For those viewing this battle from a distance, the continued unsuccessful attempts at novel therapies for this disease may be difficult to understand. However, for those treating these patients, and certainly for the patients themselves, the importance and urgency of each attempt is clear.
The Design and Development of Deferiprone (L1) and Other Iron Chelators for Clinical Use: Targeting Methods and Application Prospects (2004)

Iron is essential for all human cells as well as neoplastic cells and invading microbes. Natural and synthetic iron chelators could affect biological processes involving iron and other metal ions in health and disease states. Iron overload is the most common metal toxicity condition worldwide. There are currently two iron chelating drugs, which are mostly used for the treatment of thalassaemia and other conditions of transfusional iron overload. Deferoxamine was until recently the only approved iron chelating drug, which is effective but very expensive and administered parenterally resulting in low compliance. Deferiprone (L1 or 1,2-dimethyl-3-hydroxypyrid-4-one) is the world's first and only orally active iron chelating drug, which is effective and inexpensive to synthesise thus increasing the prospects of making it available to most thalassaemia patients in third world countries who are not currently receiving any form of chelation therapy. Deferiprone has equivalent iron removal efficacy and comparable toxicity to deferoxamine. There are at least four other known iron chelators, which are currently being developed. Even if successful, these are not expected to become available for clinical use in the next five years and to be as inexpensive as deferiprone. The variation in the chemical, biological, pharmacological, toxicological and other properties of the chelating drugs and experimental chelators provide evidence of the difference in the mode of action of chelators and the need to identify and select molecular structures and substituents based on structure/activity correlations for specific pharmacological activity. Such information may increase the prospects of designing new chelating drugs, which could be targeted and act on different tissues, organs, proteins and iron pools that play important role not only in the treatment of iron overload but also in other diseases of iron and other metal imbalace and toxicity including free radical damage. Chelating drugs could also be designed, which could modify the enzymatic activity of iron and other metal containing enzymes, some of which play a key role in many diseases such as cancer, inflammation and atherosclerosis. Other applications of iron chelating drugs could involve the detoxification of toxic metals with similar metabolic pathways to iron such as Al, Cu, Ga, In, U and Pu.
Book reviews (1993)

Eamon Duffy, The Stripping of the Altars, Traditional Religion in England 1400–1580. New Haven, CT, Yale University Press, 1992, 654 pp. ISBN 0–300–053425–8. Harvey Ferguson, Religious Transformation in Western Society: The End of Happiness. London and New York, Routledge, 1992, xvi, 269 pp. ISBN 0–415–02574–5. Religiones Latinoamericanas 1 (Religiones: Cuestiones Tcoricometodoiogicas), Mexico City, Asociación Latinoamericana para el Estudio de las Religiones. January‐June 1991. Revista de Estudios Budistas I, 1, Mexico City, Asociación Latinoamericana de Estudios Budistas. April 1991. Koichi Shinohara and Gregory Schopen (eds), From Benares to Beijing: Essays on Buddhism and Chinese Religion. Canada, Mosaic Press, 1992, 304 pp. ISBN 0–88962–443–7. Robert E. Buswell, Jr and Robert M. Gimello (eds), Paths to Liberation: The Mārga and its Transformations in Buddhist Thought. Honolulu: Kuroda Institute, University of Hawaii Press, 1992, ix, 525 pp. Susan Grossman and Rivka Haut (eds), Daughters of the King: Women and the Synagogue. New York, The Jewish Publication Society, 1992, i‐340 pp. ISBN 0–8276–0395–9. Akbar S. Ahmed, Resistance and Control in Pakistan. London, Routledge, 1991. 2nd edition, first published in 1983 under the tide Religion and Politics in Muslim Society. Cambridge, Cambridge University Press, xx + 207 pp., £12.99 (paperback). ISBN 0–415–05797–3. Garry Wills, Under God: Religion and American Politics. New York and London, Simon and Schuster, 1990, 445 pp., £17.99 (hardback), £9.99 (paperback). J. Andrew Overman and Robert S. MacLennan (eds), Diaspora Jews and Judaism: Essays in Honor of and in Dialogue with, A. Thomas Kraabel. South Florida Studies in the History of Judaism 41, Atlanta, GA, Scholars Press, 1992, xviii + 368 pp., no price given. ISBN 1 55540 696 3. Christine Trevett, Women and Quakerism in the 17th Century. York, Sessions Book Trust, The Ebor Pess, 1991, 171 pp. Jan Peter Schouten, Revolution of the Mystics: On the Social Aspects of Viraiaivism. Kampcn, The Netherlands, Kok Pharos Publishing House, 1991, xiii + 331 pp. ISBN 90 242 3425 5. Michael L. Budde, The Two Churches: Catholicism and Capitalism in the World System. Durham, NC, Duke University Press, 1992, 172 pp., £25.00. ISBN 0–8223–1229–8. Teun Goudriaan (ed.), Ritual and Speculation in Early Tantrism: Studies in Honor of André Padoux. SUNY Series in Tantric Studies, Albany, NY, State University of New York Press, 1992, xv + 359 pp. ISBN 0–7914–0898–1. Robert S. Shepard, God's People in the Ivory Tower: Religion in the Early American University. Brooklyn, Carlson, 1991, 174 pp. $50.00. ISBN 0–926019–56–2.
Chloride uptake into cultured airway epithelial cells from cystic fibrosis patients and normal individuals. (1985)

The chloride permeability of airway and sweat ductal epithelium of cystic fibrosis (CF) patients is decreased. This abnormality could represent an intrinsic characteristic of the epithelial cell or the response to a tonic extrinsic stimulus, in vivo. We cultured airway epithelial cells derived from CF and non-CF individuals under identical conditions that were free from donor-specific factors. Differences in the characteristics of cells that multiplied under these circumstances are unlikely to reflect the effects of extrinsic modulation present in the host. After 8-12 days in culture, the cells of CF and non-CF patients were similar in morphology and intracellular electrolyte content, but the CF cultures took up chloride at a reduced rate. The difference could not be attributed to a higher intracellular potential in CF cells or to the presence of a stilbene anion-sensitive chloride-chloride exchange in non-CF cells. We conclude that epithelial cells from CF patients grown in the absence of extracellular factors of the host express reduced cellular chloride permeability, a defect similar to that found in vivo and in freshly excised nasal epithelium.