gebhart/patrepeval huggingface dataset:
Equilibrium denaturation of human growth hormone and its cysteine-modified forms. (1990)

The equilibrium denaturation of human growth hormone (hGH) derived from heterologous gene expression in Escherichia coli was studied. Denaturation was measured by ultraviolet absorbance, intrinsic fluorescence, far ultraviolet circular dichroism, and size exclusion chromatography. The denaturation transitions obtained from each method of detection were coincident, indicating a two-state denaturation mechanism. The denaturation transitions were independent of the concentration of protein. The Gibbs free energy of unfolding is 14.5 +/- 1 kcal/mol. Human growth hormone contains two disulfide bridges between residues 53-165 (large loop) and 182-189 (small loop). The small loop was selectively reduced and cysteines alkylated with iodoacetic acid or iodoacetamide. The tetra-S-carbamidomethylated and tetra-S-carboxymethylated derivatives were also prepared. All S-alkylated hGH forms were indistinguishable from the native conformations in the absence of denaturant by far ultraviolet circular dichroism. The circular dichroism-detected equilibrium denaturation of each derivative was determined and the Gibbs free energy of unfolding of the tetra-S-modified forms was 5.3 +/- 0.5 kcal/mol and of the di-S-alkylated derivatives was 11.2 +/- 0.8 kcal/mol. These results for hGH are different than previously obtained results for bovine, ovine, and rat growth hormones. Stable equilibrium intermediates have been identified for these non-human species of growth hormone. The stable intermediates observed in the denaturation of reduced, alkylated hGH or nonhunam growth hormones are similar and characterized as compact, helical, lacking native-like tertiary structure, and having a tendency to aggregate. The apparent absence of intermediates in the folding of oxidized hGH is due to the relative instability of intermediates compared with their native structures. The hGH conformation is at least 5 kcal/mol more stable than the growth hormones from other species. Reduction and alkylation of the disulfide bridges of hGH diminish the stability differences between the native and intermediate states, such that the denaturation behavior is similar to the nonhuman growth hormones with well-populated intermediates. Most proteins do not demonstrate equilibrium folding intermediates presumably because intermediates are only marginally stable in conditions that disrupt the native state. The folding results with hGH and alkylated hGH substantiate this.
Vaccination-Induced Autoimmune Vitiligo Is a Consequence of Secondary Trauma to the Skin (2004)

A major concern for cancer vaccines targeting self-tumor antigens is the risk of autoimmune sequelae. Although antitumor immunity correlates with autoimmune disease in some preclinical models, the mechanism(s) linking antitumor immunity and subsequent autoimmune pathology remain(s) to be determined. In the current study, we demonstrated that intradermal (i.d.) immunization with a recombinant adenovirus (Ad) expressing the murine melanoma antigen tyrosinase-related protein 2 (AdmTrp-2) results in a moderate level of tumor protection against the B16F10 murine melanoma without any vitiligo. Similar immunization with an Ad encoding human Trp-2 (AdhTrp-2) resulted in 50-fold greater protective immunity and produced vitiligo in all of the mice, suggesting that the development of autoimmunity may reflect the potency of the vaccine. Interestingly, delivery of AdhTrp-2 by i.m. injection generated protective immunity comparable with that seen in mice that received the vaccine by the i.d. route, but none of the recipients in the i.m. group developed vitiligo. The cellular and humoral responses in the i.m. immunized mice were greater than in the i.d. group; therefore, the lack of vitiligo was not caused by reduced efficacy of the vaccine. These results led us to hypothesize that vaccine-induced vitiligo was associated with local inflammatory responses. Mice immunized i.m. with AdhTrp-2 did develop vitiligo when they subsequently were injected i.d. with either a control Ad vector or complete Freund's adjuvant, suggesting that vitiligo is initiated by some form of trauma within the skin. Our data demonstrated that autoimmune pathology is not an unavoidable outcome of effective cancer vaccines directed against self-tumor antigens.
Starved and Asphyxiated: How Can CD8+ T Cells within a Tumor Microenvironment Prevent Tumor Progression (2016)

Although cancer immunotherapy has achieved significant breakthroughs in recent years, its overall efficacy remains limited in the majority of patients. One major barrier is exhaustion of tumor antigen-specific CD8(+) tumor-infiltrating lymphocytes (TILs), which conventionally has been attributed to persistent stimulation with antigen within the tumor microenvironment (TME). A series of recent studies have highlighted that the TME poses significant metabolic challenges to TILs, which may contribute to their functional exhaustion. Hypoxia increases the expression of coinhibitors on activated CD8(+) T cells, which in general reduces the T cells' effector functions. It also impairs the cells' ability to gain energy through oxidative phosphorylation. Glucose limitation increases the expression of programed cell death protein-1 and reduces functions of activated CD8(+) T cells. A combination of hypoxia and hypoglycemia, as is common in solid tumors, places CD8(+) TILs at dual metabolic jeopardy by affecting both major pathways of energy production. Recently, a number of studies addressed the effects of metabolic stress on modulating CD8(+) T cell metabolism, differentiation, and functions. Here, we discuss recent findings on how different types of metabolic stress within the TME shape the tumor-killing capacity of CD8(+) T cells. We propose that manipulating the metabolism of TILs to more efficiently utilize nutrients, especially during intermittent periods of hypoxia could maximize their performance, prolong their survival and improve the efficacy of active cancer immunotherapy.
Characterization of a 16-channel optical/electronic selector for fast packet-switched WDMA networks (1994)

We report the demonstration of a 16-channel optical/electronic selector for applications in fast packet-switched wavelength division multi-access networks. The selector chip has four differential transimpedance amplifiers with each amplifier shared by four photodetectors, giving a total of 16 channels selected by two stages of MESFET switches. The channel switching time is approximately 10 ns. No appreciable crosstalk is observed from neighboring channels in the first-stage switches, and a 0.35 dB crosstalk penalty is measured through the second-stage switches at a BER of 10/sup -9/ with -20 dBm average optical power in the interference channel. The selector can also be reconfigured as an unswitched four-channel array receiver.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Tobacco mosaic virus: a pioneer to cell–to–cell movement (1999)

Cell-to-cell movement of tobacco mosaic virus (TMV) is used to illustrate macromolecular traffic through plant intercellular connections, the plasmodesmata. This transport process is mediated by a specialized viral movement protein, P30. In the initially infected cell, P30 is produced by transcription of a subgenomic RNA derived from the invading virus. Presumably, P30 then associates with a certain proportion of the viral RNA molecules, sequestering them from replication and mediating their transport into neighbouring uninfected host cells. This nucleoprotem complex is targeted to plasmodesmata, possibly via interaction with the host cell's cytoskeleton. Prior to passage through a plasmodesma, the plasmodesmatal channel is dilated by the movement protein. It is proposed that targeting of P30-TMV RNA complexes to plasmodesmatal involves binding to a specific cell-wall-associated receptor molecule. This protein, designated p38, also functions as a protein kinase, phosphorylating P30 at its carboxy-terminus and minimizing P30-induced interference with plasmodesmatal permeability during viral infection.
Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome (2020)

Dravet syndrome (DS) is an intractable developmental and epileptic encephalopathy caused largely by de novo variants in the <i>SCN1A</i> gene, resulting in haploinsufficiency of the voltage-gated sodium channel α subunit Na<sub>V</sub>1.1. Here, we used Targeted Augmentation of Nuclear Gene Output (TANGO) technology, which modulates naturally occurring, nonproductive splicing events to increase target gene and protein expression and ameliorate disease phenotype in a mouse model. We identified antisense oligonucleotides (ASOs) that specifically increase the expression of productive <i>Scn1a</i> transcript in human cell lines, as well as in mouse brain. We show that a single intracerebroventricular dose of a lead ASO at postnatal day 2 or 14 reduced the incidence of electrographic seizures and sudden unexpected death in epilepsy (SUDEP) in the F1:129S-<i>Scn1a</i> <sup>+/-</sup> × C57BL/6J mouse model of DS. Increased expression of productive <i>Scn1a</i> transcript and Na<sub>V</sub>1.1 protein was confirmed in brains of treated mice. Our results suggest that TANGO may provide a unique, gene-specific approach for the treatment of DS.
Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom. (1991)

Recurrence or progression of intracranial tumours and potentially avoidable metabolic consequences of hypopituitarism were the main causes of death. Growth hormone treatment probably did not contribute to new tumour development. Creutzfeldt-Jakob disease after pituitary growth hormone treatment continues to occur in the United Kingdom. This cohort must remain under long term review.
Analysis of the Gene Cluster Encoding Toluene/ o -Xylene Monooxygenase from Pseudomonas stutzeri OX1 (1998)

ABSTRACT The toluene/ o -xylene monooxygenase cloned from Pseudomonas stutzeri OX1 displays a very broad range of substrates and a very peculiar regioselectivity, because it is able to hydroxylate more than one position on the aromatic ring of several hydrocarbons and phenols. The nucleotide sequence of the gene cluster coding for this enzymatic system has been determined. The sequence analysis revealed the presence of six open reading frames (ORFs) homologous to other genes clustered in operons coding for multicomponent monooxygenases found in benzene- and toluene-degradative pathways cloned from Pseudomonas strains. Significant similarities were also found with multicomponent monooxygenase systems for phenol, methane, alkene, and dimethyl sulfide cloned from different bacterial strains. The knockout of each ORF and complementation with the wild-type allele indicated that all six ORFs are essential for the full activity of the toluene/ o -xylene monooxygenase in Escherichia coli . This analysis also shows that despite its activity on both hydrocarbons and phenols, toluene/ o -xylene monooxygenase belongs to a toluene multicomponent monooxygenase subfamily rather than to the monooxygenases active on phenols.
A recombinant plasmid from which an infectious adeno-associated virus genome can be excised in vitro and its use to study viral replication (1987)

A recombinant plasmid carrying an infectious adeno-associated viral genome was constructed that differs in several key respects from previously described recombinants. First, the vector is pEMBL8(+), which allows isolation of viral plus and minus strands. Second, the inserted viral sequences contain two XbaI cleavage sites that flank the viral coding domain. These inserts do not affect replication of the virus, and they allow nonviral sequences to be easily inserted between the cis-acting terminal repeats of adeno-associated virus. Third, the viral genome is flanked by PvuII cleavage sites that allow the entire, infectious viral chromosome to be excised from plasmid sequences in vitro. Viral DNA was replicated more efficiently within adenovirus-infected 293 cells if it was excised from the vector with PvuII before transfection. Presumably, the increased efficiency reflects bypass of the excision step which must normally precede replication when a recombinant plasmid enters the nucleus. The ability to bypass the excision step was exploited to search for a viral function required specifically for excision of the viral genome from the integrated state. None of the mutants tested identified a gene product required for excision that was not also essential for replication. The ability to produce pure populations of viral plus and minus strands was used to demonstrate that both strands are infectious.
Second harmonic detection of spatially filtered two-photon excited fluorescence (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSecond harmonic detection of spatially filtered two-photon excited fluorescenceWalt G. Fisher and Fred E. LytleCite this: Anal. Chem. 1993, 65, 5, 631–635Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/ac00053a024https://doi.org/10.1021/ac00053a024research-articleACS PublicationsRequest reuse permissionsArticle Views82Altmetric-Citations17LEARN 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
The Army Research Laboratory ultra-wide band testbed radars (2002)

In 1988, the Army Research Laboratory (ARL) began a research program to determine the feasibility of bringing emerging technologies together to analyze the problem of seeing through an inhomogeneous medium such as tree/foliage cover or the ground. The results of these studies indicated that continuing work in this area and sponsoring enabling technologies could produce a realizable system, thus leading to an understanding of the physics associated with foliage and ground penetration radar. Based on technology available in 1988, ARL instrumented an ultra-wideband (UWB) synthetic aperture radar (SAR) to collect data supportive of foliage penetration (FOPEN) and ground penetration (OPEN) studies. These programs are aimed at measuring and analyzing the basic phenomenology of impulse radar, specifically the propagation effects of targets, clutter, and targets embedded in clutter. At the time, the system developed at ARL lacked real-time data collection capability. Low transmit-power and the relatively slow data-transfer rates from the A/D converter to the data archiving system resulted in a system that needed many pulses to coherently integrate the power up, produced large amounts of collected data, and require a 50-hour data collection period. Today, by taking advantage of commercial off-the-shelf processors, an advanced A/D converter, a more powerful transmitter, and lessons learned, the authors have designed and assembled a more capable impulse implementation. The paper describes this upgraded radar system and the associated components used in the radar.
Treatment of Vasculogenic Sexual Dysfunction with Pentoxifylline (1993)

These promising preliminary results suggest a well tolerated alternative therapy for erectile dysfunction in patients with mild to moderate penile vascular disease.
Involvement of advanced glycation end product-induced asymmetric dimethylarginine generation in endothelial dysfunction (2013)

Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, plays a role in endothelial dysfunction, an initial step of atherosclerosis. Advanced glycation end products (AGEs) also contribute to accelerated atherosclerosis. However, a pathophysiological crosstalk between ADMA and AGEs remains unclear. In this study, we investigated the relationship between ADMA and AGE level in patients with end-stage renal disease (ESRD) due to diabetic nephropathy. We also examined whether and how AGEs increased ADMA generation by cultured endothelial cells (ECs). Plasma ADMA levels were positively associated with serum AGE level and were inversely correlated with endothelial function determined by flow-mediated vasodilatation. AGEs dose dependently increased reactive oxygen species (ROS) generation in ECs, which was blocked by antisense DNA raised against receptor for AGEs (RAGE). Furthermore, AGEs decreased messenger RNA (mRNA) level of dimethylarginine dimethylaminohydrolase (DDAH)-II, an enzyme for ADMA degradation, reduced its total enzymatic activity and resultantly increased ADMA, all of which were completely blocked by an antioxidant, N-acetylcysteine. These results suggest that the AGE-RAGE-mediated ROS generation could be involved in endothelial dysfunction in diabetic ESRD patients partly by increasing the ADMA generation via suppression of DDAH activity in ECs.
An agent-based and spatially explicit model of pathogen dissemination in the intensive care unit* (2005)

Spatially explicit discrete element models, such as the model presented, may prove useful for analyzing the transmission of pathogens within the intensive care unit.
Alpha 4-integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep. (1994)

Eosinophils and T lymphocytes are thought to be involved in allergic airway inflammation. Both cells express the alpha 4 beta 1-integrin, very late antigen-4 (VLA-4, CD49d/CD29); alpha 4-integrins can promote cellular adhesion and activation. Therefore, we examined the in vivo effects of a blocking anti-alpha 4 monoclonal antibody, HP 1/2, on antigen-induced early and late bronchial responses, airway hyperresponsiveness, inflammatory cell influx, and peripheral leukocyte counts in allergic sheep. Sheep blood lymphocytes, monocytes, and eosinophils expressed alpha 4 and bound HP 1/2. In control sheep, Ascaris antigen challenge produced early and late increases in specific lung resistance of 380 +/- 42% and 175 +/- 16% over baseline immediately and 7 h after challenge, respectively, as well as airway hyperresponsiveness continuing for 14 d after antigen challenge. Treatment with HP 1/2 (1 mg/kg, i.v.) 30 min before antigen challenge did not affect the early increase in specific lung resistance but inhibited the late-phase increase at 5-8 h by 75% (P < 0.05) and inhibited the post-antigen-induced airway hyperresponsiveness at 1, 2, 7, and 14 d (P < 0.05, for each time). Intravenous HP 1/2 given 2 h after antigen challenge likewise blocked late-phase airway changes and postchallenge airway hyperresponsiveness. Airway administration of HP 1/2 (16-mg dose) was also effective in blocking these antigen-induced changes. Response to HP 1/2 was specific since an isotypic monoclonal antibody, 1E6, was ineffective by intravenous and aerosol administration. Inhibition of leukocyte recruitment did not totally account for the activity of anti-alpha 4 antibody since HP 1/2 neither diminished the eosinopenia or lymphopenia that followed antigen challenge nor consistently altered the composition of leukocytes recovered by bronchoalveolar lavage. Because airway administration of HP 1/2 was also active, HP 1/2 may have inhibited cell activation. Reduction of platelet-activating factor-induced eosinophil peroxidase release from HP 1/2-treated eosinophils supports such a mechanism. These findings indicate a role for alpha 4-integrins in processes that lead to airway late phase responses and persisting airway hyperresponsiveness after antigen challenge.
Bis(oxazolines) as chiral ligands in metal-catalyzed asymmetric reactions. Catalytic, asymmetric cyclopropanation of olefins (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBis(oxazolines) as chiral ligands in metal-catalyzed asymmetric reactions. Catalytic, asymmetric cyclopropanation of olefinsDavid A. Evans, Keith A. Woerpel, Mira M. Hinman, and Margaret M. FaulCite this: J. Am. Chem. Soc. 1991, 113, 2, 726–728Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/ja00002a080https://doi.org/10.1021/ja00002a080research-articleACS PublicationsRequest reuse permissionsArticle Views8688Altmetric-Citations853LEARN 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
Hydration of complexone complexes of lanthanide cations (1980)

The 1H n.m.r. spectra of some lanthanide(III) complexone complexes have been studied. The investigation showed that these complexes exist in states of fast exchange between different conformations on the surface of the metal ion. Measurements of the relaxation enhancements of water in the presence of these complexes showed a general decrease in the enhancements with increasing denticity of the ligands. This decrease was generally directly related to the hydration number of the complexes, but was also dependent on changes in electron-spin relaxation rates in different complexes.
OPALS: An optical communications technology demonstration from the International Space Station (2013)

Optical communication using space borne lasers has long promised to increase the amount of science data transmitted down to Earth. A first step in achieving operational capability is demonstrating the fundamentals of the optical link in an equivalent environment. The International Space Station, with its vast capability, is well suited to accommodate payloads aimed at advancing the readiness of such technologies.