gebhart/patrepeval huggingface dataset:
Sindbis virus expression vectors: packaging of RNA replicons by using defective helper RNAs (1993)

Since the recovery of infectious RNA transcripts from full-length cDNA clones, alphavirus genome RNAs have been engineered to allow expression of heterologous RNAs and proteins. The highest levels of expression of heterologous products are achieved when the viral structural genes are replaced by the heterologous coding sequences. Such recombinant RNAs are self-replicating (replicons) and can be introduced into cells as naked RNA, but they require trans complementation to be packaged and released from cells as infectious virion particles. In this report, we describe a series of defective Sindbis virus helper RNAs which can be used for packaging Sindbis virus RNA replicons. The defective helper RNAs contain the cis-acting sequences required for replication as well as the subgenomic RNA promoter which drives expression of the structural protein genes. In cells cotransfected with both the replicon and defective helper RNAs, viral nonstructural proteins translated from the replicon RNA allow replication and transcription of the defective helper RNA to produce the virion structural proteins. A series of defective helper RNAs were compared for the ability to package the replicon RNA as well as for the ability to be replicated and packaged. One defective helper RNA not only packaged the replicon but also was itself encapsidated and would be useful under conditions in which extensive amplification is advantageous. Other defective helper RNAs were able to package the replicon efficiently but were packaged very poorly themselves. These helpers should be useful for applications in which expression of the viral structural proteins or virus spread is not desired.
Gene Delivery Systems in Surgery (1993)

Increased understanding of the genetic basis of human disease has led to a number of potential gene-based therapies for various medical and surgical disorders. The development of efficient methods for delivering genes to mammalian cells in vitro has increased the potential clinical utility of gene-based therapies; however, a major focus of research has been more efficient delivery to appropriate target cells, in vivo as well as in vitro, to establish gene therapy as an effective clinical modality for common disorders. Despite substantial progress, a number of critical technical issues to enhance and optimize not only gene transfer but also gene expression must be resolved. These future technological developments will be essential for the widespread clinical implementation of gene-based therapy.
Gene replacement strategies for lung cancer (1998)

Considerable evidence has accumulated that cancer has a genetic origin based on the development of somatic mutations in families of genes responsible for critical functions of cellular DNA repair, growth control, and division. Restoration of the function of a single pivotal gene product appears sufficient to mediate antitumor effects that are potentially clinically significant. For example, restoration of wild-type p53 function in the cancer cell by gene transfer is sufficient to cause either cell-cycle arrest or apoptosis. This effect is not restricted to p53 but has been observed for oncogenes and other tumor suppressor genes as well. Genes can be delivered with sufficient efficiency by direct intratumoral injection to mediate tumor regression as shown in preclinical studies and phase I clinical trials in non-small cell lung cancer. Although clinical trials of gene replacement are in the earliest stages, this treatment offers a unique mechanism of action with a potentially high therapeutic index.
Reversible Alopecia Universalis During Treatment with PEG-Interferon and Ribavirin for Chronic Hepatitis C (2005)

The combination of PEG-interferon and ribavirin is currently recommended for the treatment of chronic hepatitis C, which is a common cause of morbidity and mortality worldwide. Hair disorders have often been described during interferon therapy, which include reversible hair discoloration, hypertricosis and alopecia. Ribavirin is reported to cause photoallergic reactions. We report two cases of alopecia universalis, with complete hair loss extended to the whole body, secondary to PEG-interferon and ribavirin combination therapy for chronic hepatitis C virus infection. Both female patients were infected by genotype 1 and presented alopecia during the second half of a 48-week therapy, concurrently with low levels of ferritin and thyroid dysfunction (patient 1) or depression (patient 2). Patient 1 withdrew from the therapy on week 26 and, due to the occurrence of maculo-erythematous cutaneous eczema, underwent corticosteroid therapy with complete hair regrowth. Patient 2 completed the scheduled therapy and showed a spontaneous complete hair regrowth. It should be noted that in spite of an early (within 4 weeks of therapy) virological response, patient 1 had a disease relapse after therapy withdrawal and corticosteroid therapy, while patient 2 maintained a sustained virological response. In conclusion, interferon therapy may trigger reversible alopecia universalis in susceptible patients. However, given the benign and reversible nature of this side effect, patients who achieve a virological response should be strongly advised to complete the treatment in order to prevent disease relapse.
Activation of basophil and mast cell histamine release by eosinophil granule major basic protein. (1983)

Major basic protein (MBP) is a primary constituent of eosinophil granules. In this report, we demonstrate that MBP from human eosinophil granules initiates a nonlytic histamine release from human leukocytes. A direct effect of MBP on basophils was confirmed using purified human basophils. The kinetics of release were similar to those reported for poly-L-arginine, although MBP was less potent than poly-L-arginine of similar molecular weight. Reduction and alkylation of MBP diminished both the potency and efficacy of the molecule. Native MBP also stimulated histamine secretion from purified rat peritoneal mast cells in a manner characteristic of other polycations. These results emphasize the bidirectional nature of the basophil/mast cell-eosinophil regulatory axis.
Logic Synthesis for Quantum State Generation (2016)

Quantum computation established itself as a promising emerging technology and, hence, attracted considerable attention in the domain of computer-aided-design (CAD). However, quantum mechanical phenomena such as superposition, phase shifts, or entanglement lead to a logic model which poses serious challenges to the development of a proper design flow for quantum circuits. Consequently, researchers addressed synthesis of quantum circuits not as a single design step, but considered sub-tasks such as synthesis of Boolean components or synthesis of restricted subsets of quantum functionality. Generating a particularly desired quantum state is another of these sub-tasks. However, logic synthesis of quantum circuits accomplishing that has hardly been considered yet. In this work, we propose a generic method which automatically synthesizes a quantum circuit generating any desired quantum state from an initially given basis state. The proposed method allows for both, a theoretical determination of upper bounds as well as an experimental evaluation of the number of quantum gates needed for this important design step.
Comprehensive evaluation of isoprenoid biosynthesis regulation in Saccharomyces cerevisiae utilizing the Genome Reporter Matrix™ (1999)

Gene expression profiling is rapidly becoming a mainstay of functional genomic studies. However, there have been relatively few studies of how the data from expression profiles integrate with more classic approaches to examine gene expression. This study used gene expression profiling of a portion of the genome of Saccharomyces cerevisiae to explore the impact of blocks in the isoprenoid biosynthetic pathway on the expression of genes and the regulation of this pathway. Approximately 50% of the genes whose expression was altered by blocks in isoprenoid biosynthesis were genes previously known to participate in the pathway. In contrast to this simple correspondence, the regulatory patterns revealed by different blocks, and in particular by antifungal azoles, was complex in a manner not anticipated by earlier studies.
[The efficiency of fast track protocol in elderly patients who underwent coronary artery surgery]. (2003)

Fast track protocol in patients older than 65 years is a suitable technique by using modern cardiac surgery methods. This protocol is successfully used by selecting the suitable patients and following the patients carefully in the postoperative period.
Transgene-mediated cosuppression in the C. elegans germ line (2000)

Functional silencing of chromosomal loci can be induced by transgenes (cosuppression) or by introduction of double-stranded RNA (RNAi). Here, we demonstrate the generality of and define rules for a transgene-mediated cosuppression phenomenon in the Caenorhabditis elegans germ line. Functional repression is not a consequence of persistent physical association between transgenes and endogenous genes or of mutations in affected genes. The cosuppression mechanism likely involves an RNA mediator that defines its target specificity, reminiscent of RNAi. Cosuppression is strongly abrogated in rde-2 and mut-7 mutants, but is not blocked in an rde-1 mutant, indicating that cosuppression and RNAi have overlapping but distinct genetic requirements.
Strain and temperature sensitivity of a single-mode polymer optical fiber (2005)

We have measured the optical phase sensitivity of fiber based on poly(methyl methacrylate) under near-single-mode conditions at 632.8 nm wavelength. The elongation sensitivity is 131 +/- 3 x 10(5) rad m(-1) and the temperature sensitivity is -212 +/- 26 rad m(-1) K(-1). These values are somewhat larger than those for silica fiber and are consistent with the values expected on the basis of the bulk polymer properties.
“Tau immunotherapy: Hopes and hindrances” (2017)

Alzheimer's disease (AD) is a progressive neurological disorder having two major pathological hallmarks: the extracellular senile plaques and intracellular neurofibrillary tangles composed of amyloid beta protein and hyperphosphorylated tau respectively. Removal of protein deposits from AD brains are the newer attempts for treating AD. The major developments in this direction have been the amyloid and tau based therapeutics. While senile plaque removal employing monoclonal antibodies (mAbs) restore brain function in mouse models of AD, tau has been recently introduced as the major neurodegenerative factor mediating neural cell death. So, several research groups have focused on tau therapy. So far, the outcome of tau immunotherapy has been promising and clearance of hyperphosphorylated tau has been shown to restore the brain function in animal models. But the point is which phosphorylated tau is the most critical form to be removed from the brain, especially because removal of physiologic tau can cause neurodegenerative consequence. Recently, we have shown that phosphorylated tau at Thr231 in the cis conformation is a very early driver of neurodegeneration and cis mAb treatment efficiently restores brain structure and function in TBI models. Because of efficient therapeutic effects in mice model of TBI and considering cis pT231-tau accumulation in AD brains, it could be a very good candidate for tau immunotherapy upon several tauopathy disorders including AD.
Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer—Response (2013)

We wish to thank Radvanyi and colleagues for their excellent letter that documents the strong rationale to combine PD-1 signaling blockade with adoptively transferred antigen-specific T cells or ex vivo expanded tumor-infiltrating lymphocytes (TIL). Our review was not meant to be comprehensive and space limitations precluded mention of all potentially relevant combinations with antagonists of PD-1 signaling. In fact, the first experimental data showing the application of anti-PD-L1 antibody for the treatment of cancer were generated in an adoptive T-cell transfer model (1). Very recent data from the phase I trial of nivolumab and ipilimumab in metastatic melanoma provided evidence for the hypothesis that combining PD-1 signaling blockade with other immunotherapy agents or approaches will improve treatment outcome (2). One of our patients on the latter trial, whose disease progressed on the combination of nivolumab and ipilimumab, subsequently responded to TIL therapy administered at another center. Although only an anecdote, it suggests a relevant role for cell therapies even in this era of other highly active immune-modulating agents (2). We look forward to the clinical data from trials combining adoptive cell therapy with anti-PD1 or anti-PD-L1.See the original Letter to the Editor, p. 5541M. Sznol is a consultant/advisory board member of Bristol-Myers Squibb, Genesis Biopharma, and MedImmune. No potential conflicts of interest were disclosed by the other author.
The behavior of microring electrodes (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe behavior of microring electrodesMartin Fleischmann, Saibal Bandyopadhyay, and Stanley PonsCite this: J. Phys. Chem. 1985, 89, 25, 5537–5541Publication Date (Print):December 1, 1985Publication History Published online1 May 2002Published inissue 1 December 1985https://doi.org/10.1021/j100271a046RIGHTS & PERMISSIONSArticle Views130Altmetric-Citations67LEARN 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 InReddit PDF (474 KB) Get e-Alerts
MAXIZYMEs: Allosterically controllable ribozymes with biosensor functions (2000)

Ribozymes are catalytic RNAs that can cleave RNAs at specific sites, thus they have been employed to degrade a target mRNA in vivo. Development of allosterically controllable ribozymes is of great current interest, but it remained difficult to furnish such functions to ribozymes in cultured cells or in animals. Recently, we designed allosterically controllable ribozymes termed maxizymes, which have sensor arms that recognize target mRNA sequences and, in the presence of such target sequences only, they form a cavity that can capture catalytically indispensable ions, cleaving the target. The maxizyme was applied to therapy for chronic myelogenous leukemia (CML). It cleaved specifically the chimeric BCR-ABL mRNA, which caused CML, without damaging the normal ABL or BCR mRNA in mammalian cells and also in mice, providing the first successful example for allosteric control of the activity of artificial ribozymes in vivo.
A theoretical study on magnetic induction frequency dependence of phase shift in oedema and haematoma (2006)

The spectroscopic distribution of induction phase shift as a function of the relative volume of oedema and haematoma in the brain, lung and muscle in the bulk of tissue was produced from the available tissue data and a simple mathematical model of electromagnetic induction in tissue. The results show that the phase shift is sensitive to the relative volume of oedema/haematoma at frequencies higher than approximately 10 MHz. The effect of oedema/haematoma on brain, lung and muscle tissues is tissue-type specific. Increasing the volume of tissue has the effect of lowering the frequency at which the phase shift becomes sensitive to the volume of oedema/haematoma. The results indicate that bulk induction measurement of the phase shift has the potential for becoming a simple means for non-contact detection of formation of oedema and haematoma in brain, lung and muscle tissues.
Enzymatic Reduction of Hydrophobic β,δ-Diketo Esters (2001)

The regio- and enantioselective reduction of two hydrophobic β,δ-diketo esters is presented. Enzymatic reduction of racemic tert-butyl 4-methyl-3,5-dioxohexanoate (rac-1) with alcohol dehydrogenase from Lactobacillus brevis (recLBADH) gave δ-hydroxy-β-keto ester syn-(4S,5R)-4 under dynamic kinetic resolution conditions (99.2% ee, syn:anti = 97:3, 66% isolated yield). The highly lipophilic tert-butyl-3,5-dioxoheptanoate (2) was reduced with the same sense of enantio- and regioselectivity by recLBADH. A biphasic system was applied in this case. The product, δ-hydroxy-β-keto ester (R)-9 (98.5% ee, 66% isolated yield), was converted into (R)-6-ethyl-5,6-dihydropyran-2-one [(R)-10], which is a naturally occurring fragrance.
The Use of Estrogens and Progestins and the Risk of Breast Cancer in Postmenopausal Women (1995)

The addition of progestins to estrogen therapy does not reduce the risk of breast cancer among postmenopausal women. The substantial increase in the risk of breast cancer among older women who take hormones suggests that the trade-offs between risks and benefits should be carefully assessed.
DNA tumor virus oncoproteins and retinoblastoma gene mutations share the ability to relieve the cell's requirement for cyclin D1 function in G1. (1994)

The retinoblastoma gene product (pRB) participates in the regulation of the cell division cycle through complex formation with numerous cellular regulatory proteins including the potentially oncogenic cyclin D1. Extending the current view of the emerging functional interplay between pRB and D-type cyclins, we now report that cyclin D1 expression is positively regulated by pRB. Cyclin D1 mRNA and protein is specifically downregulated in cells expressing SV40 large T antigen, adenovirus E1A, and papillomavirus E7/E6 oncogene products and this effect requires intact RB-binding, CR2 domain of E1A. Exceptionally low expression of cyclin D1 is also seen in genetically RB-deficient cell lines, in which ectopically expressed wild-type pRB results in specific induction of this G1 cyclin. At the functional level, antibody-mediated cyclin D1 knockout experiments demonstrate that the cyclin D1 protein, normally required for G1 progression, is dispensable for passage through the cell cycle in cell lines whose pRB is inactivated through complex formation with T antigen, E1A, or E7 oncoproteins as well as in cells which have suffered loss-of-function mutations of the RB gene. The requirement for cyclin D1 function is not regained upon experimental elevation of cyclin D1 expression in cells with mutant RB, while reintroduction of wild-type RB into RB-deficient cells leads to restoration of the cyclin D1 checkpoint. These results strongly suggest that pRB serves as a major target of cyclin D1 whose cell cycle regulatory function becomes dispensable in cells lacking functional RB. Based on available data including this study, we propose a model for an autoregulatory feedback loop mechanism that regulates both the expression of the cyclin D1 gene and the activity of pRB, thereby contributing to a G1 phase checkpoint control in cycling mammalian cells.
Michael-type addition of azoles of broad-scale acidity to methyl acrylate (2011)

An optimisation of Michael-type addition of azole derivatives of broad-scale acidity - ranging from 5.20 to 15.00 pK(a) units - namely 4-nitropyrazole, 3,5-dimethyl-4-nitropyrazole, 4(5)-nitroimidazole, 4,5-diphenylimidazole, 4,5-dicyanoimidazole, 2-methyl-4(5)-nitroimidazole, 5(4)-bromo-2-methyl-4(5)-nitroimidazole and 3-nitro-1,2,4-triazole to methyl acrylate as an acceptor was carried out. The optimisation process involved the use of an appropriate basic catalyst (DBU, DIPEA, NaOH, NaH, TEDA), a donor/base/acceptor ratio and the reaction temperature. The reactions were performed in DMF as solvent. Target Michael adducts were obtained in medium to excellent yields. Importantly, for imidazole and 1,2,4-triazole derivatives, no corresponding regioisomers were obtained.
Oostatic hormone inhibits biosynthesis of midgut proteolytic enzymes and egg development in mosquitoes (1988)

Abstract Injection of partially purified oostatic hormone (0.7 μg) into female Aedes aegypti inhibited egg development, proteolytic enzyme activity, and blood digestion in the midgut, whereas control injections of saline or insulin chain A (0.7 μg) did not affect these processes. Oostatic hormone given by enema, on the other hand, did not inhibit proteolytic enzyme activity, indicating that the hormone acts outside the midgut. A single injection of oostatic hormone (0.7 μg) caused a 1.7–1.5‐fold reduction in activity of trypsinlike enzymes during blood digestion, with a 10‐h delay in peak activity. Using [1,3‐ 3 H]diisopropylfluorophosphate (DFP) in the presence of 8 mM tosylamide‐2‐phenylethyl chloromethyl ketone, the synthesis of trypsinlike derivatives was followed in the midgut of female A. aegypti. A 4‐fold reduction in [1,3‐ 3 H]diisopropylphosphoryl‐trypsinlike derivatives was noted after oostatic hormone treatment. Several isozymes that are normally synthesized were absent in the presence of DFP, as assessed by polyacrylamide gel electrophoresis. Injection of oostatic hormone into decapitated and ovariectomized females that did not synthesize ecdysteroids inhibited trypsinlike enzyme synthesis and blood digestion in the midgut, indicating that oostatic hormone inhibits the midgut cells and not the ovary or the brain's endocrine system. Comparison between oostatic hormone and soybean trypsin inhibitor indicated that the former inhibited trypsin synthesis whereas the latter inhibited trypsin activity. A. aegypti oostatic hormone is not species specific and injections of the hormone into Culex quinquefasciatus, Culex nigripalpus , and Anopheles albimanus caused inhibition of egg development, blood digestion, and synthesis of trypsinlike enzymes. A direct relation between oostatic hormone synthesis and the regulation of trypsinlike activity in the midgut is proposed.
Complementarity‐determining region 2 is implicated in the binding of staphylococcal protein A to human immunoglobulin VHIII variable regions (1993)

Staphylococcal protein A (SPA) has two distinct binding sites on human immunoglobulins. In addition to binding to the Fc region of most IgG molecules, an "alternative" binding site has been localized to the Fab region of human immunoglobulins encoded by heavy chain variable gene segments belonging to the VHIII family. Comparison of amino acid sequences of closely related SPA-binding and -non-binding proteins suggested that VHIII-specific residues in the second complementarity-determining region (CDR2) were likely responsible for SPA binding activity. Site-directed mutagenesis of a single amino acid residue in CDR2 converted an IgM rheumatoid factor which did not bind SPA to an SPA binder. These findings, therefore, locate a critical site involved in SPA binding to the CDR2 of human immunoglobulins encoded by VHIII family gene segments.