gebhart/patrepeval huggingface dataset:
Rapid development of nucleic acid diagnostics (2002)

There has been a significant increase, fueled by technologies front the human genome project, in the availability of nucleic acid sequence information for viruses and bacteria. This paper presents a computer-assisted process that begins with nucleic acid sequence information and produces highly specific pathogen signatures. When combined with instrumentation using the polymerase chain reaction, the resulting diagnostics are both specific and sensitive. The computational and engineering aspects of converting raw sequence data into pathogen-specific and instrument-ready assays are presented. Examples and data are presented for specific pathogens, including foot-and-mouth disease virus and the human immunodeficiency virus.
Evolutionary dynamics of CRISPR gene drives (2017)

The alteration of wild populations has been discussed as a solution to a number of humanity's most pressing ecological and public health concerns. Enabled by the recent revolution in genome editing, clustered regularly interspaced short palindromic repeats (CRISPR) gene drives-selfish genetic elements that can spread through populations even if they confer no advantage to their host organism-are rapidly emerging as the most promising approach. However, before real-world applications are considered, it is imperative to develop a clear understanding of the outcomes of drive release in nature. Toward this aim, we mathematically study the evolutionary dynamics of CRISPR gene drives. We demonstrate that the emergence of drive-resistant alleles presents a major challenge to previously reported constructs, and we show that an alternative design that selects against resistant alleles could greatly improve evolutionary stability. We discuss all results in the context of CRISPR technology and provide insights that inform the engineering of practical gene drive systems.
Highly enantioselective epoxidation catalysts derived from 1,2-diaminocyclohexane (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHighly enantioselective epoxidation catalysts derived from 1,2-diaminocyclohexaneEric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li DengCite this: J. Am. Chem. Soc. 1991, 113, 18, 7063–7064Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://pubs.acs.org/doi/10.1021/ja00018a068https://doi.org/10.1021/ja00018a068research-articleACS PublicationsRequest reuse permissionsArticle Views18059Altmetric-Citations896LEARN 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
Upper Airway Anesthesia Reduces Phasic Genioglossus Activity During Sleep Apnea (1997)

We hypothesize that stimulation of upper-airway mechanoreceptors during obstructive apnea augments upper airway muscle activity. If so, upper-airway anesthesia (UAA) should reduce mechanoreceptor output and therefore upper-airway muscle activity. To test this hypothesis, we studied the effect of UAA on the relationship between the phasic activity of the moving-time average (MTA) of the genioglossus electromyogram (EMG-GG) and the esophageal pressure deflection (DP) during obstructive apneas in non-rapid-eye-movement (NREM) sleep in a group of six men with severe sleep apnea. Before UAA, the phasic EMG-GG was linearly related to the deflections in esophageal pressure (DP) during the last three occluded breaths (both progressively increased). After UAA, the mean ratio of EMG-GG to DP decreased to 23% of the control value, from 0.17 +/- 0.04 to 0.04 +/- 0.01 (mean +/- SEM) arbitrary units/cm H2O (p < 0.05). The mean slope of the EMG-GG-versus-DP regression lines also decreased to 23% of the control value, from 0.22 +/- 0.03 to 0.05 +/- 0.01 arbitrary units/ cm H2O (p < 0.01). These findings suggest that stimulation of upper-airway mechanoreceptors during obstructive apnea in NREM sleep augments phasic genioglossus activity.
The role of free radicals in the pathogenesis of rheumatoid arthritis. (2003)

Free radicals are reactive chemical species that differ from other compounds in that they have unpaired electrons in their outer orbitals. They are capable of damaging cellular components, and accumulating evidence suggests that they may contribute to various disease entities including inflammatory joint disease. Reactive oxygen species (ROS) as well as reactive nitrogen species (RNS) can directly or indirectly damage basic articular constituents and lead to the clinical expression of the inflammatory arthritis. Hydroxyl radicals degrade isolated proteoglycans, and HOCl fragments collagen. Hydrogen peroxide, which is very diffusible, readily inhibits cartilage proteoglycan synthesis, e.g. by interfering with ATP synthesis, in part by inhibiting the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase in chondrocytes, aggravating the effects of proteolytic and free-radical-mediated cartilage degradation. Peroxynitrite and HOCl may facilitate cartilage damages by inactivating TIMPs. TIMP-1 inhibits stromelysins, collagenases and gelatinases and this ability is lost after ONOO(-) or HOCl treatment. HOCl can also activate latent forms of neutrophil collagenases and gelatinase with obvious consequences. Hypochlorous acid, ONOO(-) and O(2)(*-) react with ascorbate, which is essential for cartilage function, leading to low levels of ascorbate in synovial fluid. Low concentrations of H2O(2), O(2)(*-) or both, accelerate bone resorption by osteoclasts, whereas NO. inhibits it. NO. promotes chondrocyte apoptosis, inhibits proteoglycan synthesis and activates latent metalloproteinases and cyclooxygenase. ROS, produced by activated phagocytes, could alter the antigenic behaviour of immunoglobulin G, producing fluorescent protein aggregates that can further activate phagocytic cells. Radical-exposed IgG is able to bind rheumatoid factor and results in the generation of C3alpha. This reaction may be self-perpetuating within the rheumatoid joint, suggesting that free radicals play a role in the chronicity of the inflammatory reaction which is a key question regarding to which extent free radicals contribute to the consequences of inflammation, such as the cartilage and bone destruction. Reactive oxygen intermediates can also function as signaling messengers to activate transcription factors, like NFkB and AP-1, and induce gene expression. All this knowledge might serve to apply a rational selection of antioxidants for possible therapeutic purposes, enforcing combination therapy of the inflammatory joint disease.
Alterations in Myocardial Cardiolipin Content and Composition Occur at the Very Earliest Stages of Diabetes:  A Shotgun Lipidomics Study (2007)

Recently, we have identified the dramatic depletion of cardiolipin (CL) in diabetic myocardium 6 weeks after streptozotocin (STZ) injection that was accompanied by increases in triacylglycerol content and multiple changes in polar lipid molecular species. However, after 6 weeks in the diabetic state, the predominant lipid hallmarks of diabetic cardiomyopathy were each present concomitantly, and thus, it was impossible to identify the temporal course of lipid alterations in diabetic myocardium. Using the newly developed enhanced shotgun lipidomics approach, we demonstrated the dramatic loss of abundant CL molecular species in STZ-treated hearts at the very earliest stages of diabetes accompanied by a profound remodeling of the remaining CL molecular species including a 16-fold increase in the content of 18:2-22:6-22:6-22:6 CL. These alterations in CL metabolism occur within days after the induction of the diabetic state and precede the triacylglycerol accumulation manifest in diabetic myocardium. Similarly, in ob/ob mice, a dramatic and progressive redistribution from 18:2 FA-containing CL molecular species to 22:6 FA-containing CL molecular species was also identified. Collectively, these results demonstrate alterations in CL hydrolysis and remodeling at the earliest stages of diabetes and are consistent with a role for alterations in CL content in precipitating mitochondrial dysfunction in diabetic cardiomyopathy.
Research on vocabulary assessment (2000)

In the previous chapter, we saw how tests play a role in research on vocabulary within the field of second language acquisition (SLA). Now we move on to consider research in the field of language testing, where the focus is not so much on understanding the processes of vocabulary learning as on measuring the level of vocabulary knowledge and ability that learners have reached. Language testing is concerned with the design of tests to assess learners for a variety of practical purposes that can be summarised under labels such as placement, diagnosis, achievement and proficiency. However, in practice this distinction between second language acquisition research and assessment is difficult to maintain consistently, because, on the one hand, language testing researchers have paid relatively little attention to vocabulary tests and, on the other hand, second language acquisition researchers working on vocabulary acquisition have often needed to develop tests as an integral part of their research design. Thus, some of the important work on how to measure vocabulary knowledge and ability has been produced by vocabulary acquisition researchers rather than language testers; the latter have tended either to take vocabulary tests for granted or, in the 1990s, to be interested in more integrative and communicative measures of language proficiency.
Overview of Time-Base Correction Techniques and their Applications (1976)

The advent of high-performance electromechanical servo systems and of an electronically variable delay-line (EVDL)-type time-base corrector for videotape recorders (VTRs) made recovery of a properly phased color video possible in the early 1960s. The development of the video digitization and memory technique in the late 1960s produced a digital time-base corrector (DTBC) of expanded capture range at a commercially acceptable cost. Use of VTR systems with the color-under technique, with its acceptable color video performance, operational economy and simplicity, has become widespread in many non-broadcast fields as well as in the electronic newsgathering field. An important application of DTBC is for color-under VTRs, and many variations of DTBCs are being developed to further improve the performance when used with VTRs. A DTBC is also a useful ancillary element of high-performance VTRs, including quadruplex types.
Extraction of Renilla-type luciferin from the calcium-activated photoproteins aequorin, mnemiopsin, and berovin. (1975)

Photoproteins, which emit light in an oxygen-independent intramolecular reaction initiated by calcium ions, have been isolated from several bioluminescent organisms, including the hydrozoan jellyfish Aequorea and the ctenophore Mnemiopsis. The system of a related anthozoan coelenterate, the sea pansy Renilla reniformis, however, is oxygen dependent, requiring two organic components, luciferin and luciferase. Previously published indirect evidence indicates that photoproteins may contain a Renilla-type luciferin. We have now extracted in high yield a Renilla-type luciferin from three photoproteins, aequorin (45% yield), mnemiopsin (98% yield), and berovin (85% yield). Photoprotein luciferin, released from the holoprotein by mercaptoethanol treatment and separated from apo-photoprotein by gel filtration, no longer responds to calcium but now requires luciferase and O2 for light production. Photoprotein luciferin is identical to Renilla luciferin with respect to reaction kinetics and bioluminescence spectral distribution. In view of these results, the generally accepted hypothesis that the photoprotein chromophore is a protein-stabilized hydroperoxide of luciferin must be modified. We believe, instead, that the chromophore is free luciferin and that oxygen is bound as an oxygenated derivative of an amino-acid side chain of the protein. We propose the general term "coelenterate luciferin" to describe the light-producing chromophore from all bioluminescent coelenterates and ctenophores.
Refractive index of meibomian and other lipids (1986)

The refractive indices of human and rabbit meibomian secretions, and of several natural lipid mixtures and eye ointments, have been measured as a function of temperature and wavelength. A value of 1.482 was found for meibomian oil at typical eye surface temperature, but varies in humans between ca. 1.46 and 1.53 over the visible spectrum.
T-Cell Receptor Stimulation Elicits an Early Phase of Activation and a Later Phase of Deactivation of the Transcription Factor NFAT1 (1996)

We show here that NFAT1 is rapidly activated, then slowly deactivated, by stimulation of T cells through their antigen receptor. Within minutes of T-cell receptor stimulation, NFAT1 is dephosphorylated, translocates from the cytoplasm into the nucleus, and shows an increase in its ability to bind to DNA. These changes are dependent on calcium mobilization and calcineurin activation, since they are also elicited by ionomycin and are blocked by the immunosuppressive drug cyclosporin A. After several hours of T-cell receptor stimulation, the majority of the NFAT1 in the cell reverts to its original phosphorylated form, reappears in the cytoplasm, and again displays a low affinity for DNA. Deactivation of NFAT1 is facilitated by phorbol 12-myristate 13-acetate and inhibitors of capacitative calcium entry and most likely reflects the slow return of intracellular free calcium concentrations towards resting levels. Our results suggest that calcineurin-dependent signalling pathways mediate the early activation of NFAT1, while phorbol 12-myristate 13-acetate-dependent feedback pathways contribute to the late deactivation. Persistent NFAT-dependent cytokine gene transcription in activated T cells may be mediated by other NFAT family proteins in addition to NFAT1 during the immune response.
Image contrast enhancement using genetic algorithm (2003)

Proposes a method to enhance the contrast of a gray image using the genetic algorithm that measures the fitness of an individual by evaluating the intensity of spatial edges included in the image. By the ability of the genetic algorithm to search a solution in a global space, a relation between input and output gray levels is determined to convert an original gray image to an enhanced image with a good contrast. Experimental results show that the resulting images by the proposed method have good and natural contrasts compared with the resulting images by conventional methods through subjective evaluation and objective evaluation.
Analysis and prediction of antibacterial peptides (2007)

Among antibacterial peptides, there is preference for certain residues at N and C termini, which helps to demarcate them from non-antibacterial peptides. Both the termini play a crucial role in imparting the antibacterial property to these peptides. Among the methods developed, SVM shows the best performance in predicting antibacterial peptides followed by QM and ANN, in that order. AntiBP (Antibacterial peptides) will help in discovering efficacious antibacterial peptides, which we hope will prove to be a boon to combat the dreadful antibiotic resistant bacteria. A user friendly web server has also been developed to help the biological community, which is accessible at http://www.imtech.res.in/raghava/antibp/.
Bitter principles of the cucurbitaceae. I.—Observations on the chemistry of cucurbitacin a (1954)

Abstract Bitter principles have been isolated as solid foams from the fruits of several members of the Cucurbitaceae. Four bitter principles, provisionally named cucurbitacin A, B, C and D, were obtained in the crystalline state. The nature of the functional groups of cucurbitacin A, C 28 H 40 O 8 , was investigated and a detailed study of its hydrogenation has been carried out.
Introduction of Functional Groups into Peptides via <i>N</i>-Alkylation (2008)

An optimized protocol for the mild and selective Fukuyama-Mitsunobu reaction was used for mono- and di- N-alkylation on solid support. Thereby, nonfunctionalized aliphatic and aromatic residues are quickly introduced into transiently protected, primary amines of a linear peptide. N-Alkylation can also be used to implement alkyl chains carrying (protected) functionalities suited for subsequent modification. Applicability of this method is demonstrated by various N-alkylated analogues of a cyclic CXCR4 receptor antagonist originally developed by Fujii et. al.
Notes: Chromium Trichloride Tetrahydrofuranate (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNotes: Chromium Trichloride TetrahydrofuranateW Herwig and H ZeissCite this: J. Org. Chem. 1958, 23, 9, 1404Publication Date (Print):September 1, 1958Publication History Published online7 July 2003Published inissue 1 September 1958https://pubs.acs.org/doi/10.1021/jo01103a627https://doi.org/10.1021/jo01103a627research-articleACS PublicationsRequest reuse permissionsArticle Views1930Altmetric-Citations105LEARN 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
Relativism Revidivus: In Defense of Critical Relativism (1988)

Journal Article Relativism Revidivus: In Defense of Critical Relativism Get access Paul F. Anderson Paul F. Anderson Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Consumer Research, Volume 15, Issue 3, December 1988, Pages 403–406, https://doi.org/10.1086/209179 Published: 01 December 1988 Article history Received: 01 September 1987 Revision received: 01 July 1988 Published: 01 December 1988
Inhibition of macrophage phagocytosis by methylation inhibitors. Lack of correlation of protein carboxymethylation and phospholipid methylation with phagocytosis. (1985)

Adenosine (Ado), deoxyadenosine (dAdo), and adenine arabinoside (AraA) inhibit the phagocytosis of IgG-coated erythrocytes and zymosan by resident and thioglycollate-elicited macrophages (thio-macrophages) in a dose-dependent and reversible manner. 3-Deazaadenosine (3cAdo) and adenine (Ade) also inhibit the phagocytosis by resident macrophages. Homocysteine thiolactonate (Hcy) potentiates the inhibition by Ado and 3cAdo while erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) potentiates the inhibition by Ado, dAdo and AraA. This inhibition has a very rapid onset and the drugs do not interfere with the binding of IgG-coated erythrocytes to macrophages. The combination of Ado, Hcy and EHNA does not appreciably affect the intracellular level of ATP and S-adenosyl-L-methionine (AdoMet) in thio-macrophages but causes accumulations of Ado and S-adenosyl-L-homocysteine (AdoHcy) up to 135 and 145 nmol/mg of protein, respectively. During phagocytosis reversal, Ado is metabolized within 15 min while AdoHcy decreases log-arithmically with a half-life of 50 min. Carboxymethylation and phospholipid methylation, however, resume about 60-90 min after phagocytosis has recovered, and thus cannot function as transmembrane signals for phagocytosis. Other evidence showing the lack of correlation between phagocytosis and carboxymethylation inhibition include 1) Ado + Hcy inhibit carboxymethylation much better than Ado + EHNA (91 versus 75%) in thio-macrophage, but the two combinations show comparable phagocytosis inhibition potency; 2) Ado + Hcy inhibit carboxymethylation almost as well as Ado + Hcy + EHNA, but the latter is a much more effective drug combination for phagocytosis inhibition; 3) Ade and 3cAdo, although inhibiting resident macrophage phagocytosis as well as Ado + EHNA + Hcy, are much weaker carboxymethylation inhibitors; 4) dAdo and AraA potently inhibit phagocytosis but not carboxymethylation. The difference in the apparent methylation levels is not due to changes in the specific activities of AdoMet, which decrease with a half-life of 88 min. Interestingly, after the initial lag phase of about 90 min after the initiation of inhibition reversal, carboxymethylation and phagocytosis increase in parallel. In a log-log plot of carboxymethylation, phospholipid methylation, or phagocytosis versus the intracellular AdoHcy accumulation, a linear relationship is obtained. It is possible that AdoHcy accumulation is responsible for phagocytosis inhibition but inhibits by a mechanism other than interfering with protein and lipid methylations.
The Measurement of Prothrombin in Plasma (1953)

From the two-stage method carried out on the patient's plasma a method for the measurement of
Position effect variegation in Drosophila is associated with an altered chromatin structure. (1995)

A euchromatic gene placed in the vicinity of heterochromatin by a chromosomal rearrangement generally exhibits position effect variegation (PEV), a clonally inherited pattern showing gene expression in some somatic cells but not in others. The mechanism responsible for this loss of gene expression is investigated here using fly lines carrying a P element containing the Drosophila melanogaster white and hsp26 genes. Following mobilization of the P element, a screen for variegation of white expression recovered inserts at pericentric, telomeric, and fourth chromosome regions. Previously identified suppressors of PEV suppressed white variegation of pericentric and fourth chromosome inserts but not telomeric inserts on the second and third chromosomes. This implies a difference in the mechanism for gene repression at telomeres. Heat shock-induced hsp26 expression was reduced from pericentric and fourth chromosome inserts but not from telomeric inserts. Chromatin structure analysis revealed that the variegating inserts showed a reduction in accessibility to restriction enzyme digestion in the hsp26 regulatory region in isolated nuclei. Micrococcal nuclease digests showed that pericentric inserts were packaged in a more regular nucleosome array than that observed for euchromatic inserts. These data suggest that altered chromatin packaging plays a role in PEV.