gebhart/patrepeval huggingface dataset:
Functional Analysis of Amino Acid Residues Constituting the dNTP Binding Pocket of HIV-1 Reverse Transcriptase (1998)

In order to understand the functional implication of residues constituting the dNTP-binding pocket of human immunodeficiency virus type 1 reverse transcriptase, we performed site-directed mutagenesis at positions 65, 72, 113, 115, 151, 183, 184, and 219, and the resulting mutant enzymes were examined for their biochemical properties and nucleotide selectivity on RNA and DNA templates. Mutations at positions 65, 115, 183, 184, and 219 had negligible to moderate influence on the polymerase activity, while Ala substitution at positions 72 and 151 as well as substitution with Ala or Glu at position 113 severely impaired the polymerase function of the enzyme. The K219A, Y115F, and Q151M mutants had no influence on the fidelity; Y183A, Y183F, K65A, and Q151N mutants exhibited higher fidelity on both RNA and DNA templates, while Y115A was less error-prone selectively on a DNA template. Analysis of the three-dimensional model of the enzyme-template primer-dNTP ternary complex suggests that residues Tyr-183, Lys-65, and Gln-151 may have impact on the flexibility of the dNTP-binding pocket by virtue of their multiple interactions with the dNTP, template, primer, and other neighboring residues constituting the pocket. Recruitment of the correct versus incorrect nucleotides may be a function of the flexibility of this pocket. A relatively rigid pocket would provide greater stringency, resulting in higher fidelity of DNA synthesis in contrast to a flexible pocket. Substitution of a residue having multiple interactions with a residue having reduced interaction capability will alter the internal geometry of the pocket, thus directly influencing the fidelity.
Crystallization of amorphous silicon during thin-film gold reaction (1987)

The crystallization of a-Si in a-Si (50-nm) and Au (5-nm) thin-film bilayers has been investigated during heat treatment in a transmission electron microscope. When crystallization of a-Si first begins at 130 °C, the Au-Si alloy (Au and a precursor phase) reflections observed at lower temperatures vanish, and several new reflections from metastable Au-Si compounds occur. Dendritically growing islands of poly-Si are observed after heating at 175 °C. If the samples are held at a constant temperature of 175 °C for 10 min, the poly-Si islands coalesce. The formation of poly-Si depends on the diffusion of Au into a-Si and the formation of metastable Au-Si compounds, which act as transport phases for both Si and Au. After crystallization Au segregates to the front and back surfaces of the poly-Si film. The result of this work and earlier diffraction investigations are interpreted in terms of superlattices based on a sublattice. A fundamental body-centered-cubic structure with a=5.52 Å and composition Au4Si is suggested for the Au-Si compounds.
Alpha-1-antitrypsin replacement therapy: current status (2006)

There might be a possible, but so far unproven, role of alpha-1-antitrypsin augmentation therapy in reducing the progression of emphysema in subsets of patients with alpha-1-antitrypsin deficiency. Placebo-controlled, randomized clinical trials are required to draw firm conclusions. Recent advances in the understanding of the molecular pathology provide opportunities for development of new therapeutic targets for this genetic disorder.
Changing Treatment Paradigms in Metastatic Breast Cancer (2015)

Advances in understanding tumor biology, particularly signaling pathways, have led to the development and approval of many novel agents and have changed the landscape of therapy for patients with metastatic breast cancer. This review highlights some of the recent successes and failures in breast cancer drug development, including strategies to overcome endocrine and human epidermal growth factor 2-neu (HER2) resistance, targeting triple-negative breast cancers (which do not express the HER2, estrogen, and progesterone receptors) through novel receptors, harnessing the immune system, and new ways of targeting angiogenesis. For patients with metastatic breast cancer, expanding therapeutic options through clinical trial participation is a crucial part of modern oncology practice. As we continue to learn how to use targeted therapies in the context of genomic medicine, analysis of the tumor in real-time may become increasingly important, giving researchers the information needed to start combining therapies in a biologically informed manner.
Human-like antibodies neutralizing Western equine encephalitis virus (2014)

This study describes the development of the first neutralizing antibodies against Western equine encephalitis virus (WEEV), a member of the genus Alphavirus. WEEV is transmitted by mosquitoes and can spread to the human central nervous system, causing symptoms ranging from mild febrile reactions to life-threatening encephalitis. WEEV has been classified as a biological warfare agent by the US Centers for Disease Control and Prevention. No anti-WEEV drugs are currently commercially available. Neutralizing antibodies are useful for the pre- and post-exposure treatment of WEEV infections. In this study, two immune antibody gene libraries were constructed from two macaques immunized with inactivated WEEV. Four antibodies were selected from these libraries and recloned as scFv-Fc, with a human Fc part. These antibodies bound WEEV specifically in ELISA with little or no cross-reaction with other alphaviruses. They were further analyzed by immunohistochemistry. All binders were suitable for the intracellular detection of WEEV particles. Neutralizing activity was determined in vitro. Three of the four antibodies were found to be neutralizing; about 1 ng/mL of the best antibody (ToR69-3A2) neutralized 50% of 5x10(4) TCID 50/mL. Due to its human-like nature with a germinality index of 89% (VH) and 91% (VL), the ToR69-3A2 antibody is a promising candidate for future passive vaccine development.
Endometriosis (2009)

This review emphasizes the participation of estrogen and inflammation in the development of endometriosis. A feedback cycle in which prostaglandins and aromatase activity are prominent allows for the persistence of endometriotic tissue. Knowledge of this cycle has important implications for the treatment of endometriosis.
Economic Weed Control in High Plains Cotton (1990)

This study considered factors that affect the weed control efficacy and profitability of several major herbicides used in cotton ( Gossypium hirsutum L.) on the High Plains. The herbicides were Caparol 1 (N,N'‐bis{1‐methylethyl}‐6‐(methylthio)‐1,3,5‐triazine‐2,4‐diamine), Dual (2‐chloro‐N‐{2‐ethyl‐6‐methylphenyl}‐N‐{2‐methoxy‐1‐methylethyl}acetamide), Prowl (N‐{1‐ethylpropyl}‐3,4‐dimethyl‐2,6‐dinitrobenzenamine), Sancap (6‐{ethylthio}‐N,N'bis‐{1‐methylethyl}‐1,3,5‐triazine‐2,4‐diamine), and Treflan (2,6‐di‐nitro‐N,N‐dipropyl‐4‐{trifluoromethyl}benzenamine). Results indicate that: (i) little additional yield is necessary to justify the use of herbicides; (ii) conditions present when herbicides are applied and crops planted affect herbicide effectiveness (generally, higher temperatures at application and planting dates result in better control and/or higher additional yields); and (iii) in some cases farmers should reduce the manufacturers' recommended rates of herbicide application to increase their profit.
LAS PALMAS ACADÉMICAS DE FRANCIA, A DOS PROFESORAS DE LA ENP Y CCH (2004)

ROSA MARIA DUR N GILI, JEFA DEL DEPARTAMENTO DE FRANCES DE ESCUELA NACIONAL PREPARATORIA (ENP), RECIBIO LAS PALMAS ACADEMICAS QUE OTORGA FRANCIA, EN UNA CEREMONIA EFECTUADA EN EL INSTITUTO FRANCES DE AMERICA LATINA (IFAL), EL 13 DEL PRESENTE MES. ACADEMICA PREPARATORIANA EXPRESO SU SATISFACCION POR RECIBIR CONDECORACION DE MANOS DE GERARD FONTAINE, CONSEJERO DE COOPERACION Y DE ACCION CULTURAL DE EMBAJADA DE FRANCIA EN MEXICO, EN EL RECINTO AL QUE LLAMO LA CASA DE MI JUVENTUD. SENALO QUE COMENZO A TRABAJAR PROFESIONALMENTE EN EL IFAL SIENDO ADOLESCENTE; AHI APROBO SU EXAMEN DE BACHILLERATO; TUVO ALUMNOS COMO MANUELA REYES, ESPOSA DE ALFONSO REYES, SALVADOR MORENO, EL GRAN COMPOSITOR, Y A UN JOVEN MEDICO TALENTOSO, QUIEN TIEMPO DESPUES SE CONVERTIRIA EN SU ESPOSO. ASIMISMO, DIJO QUE UNO DE SUS INTERESES HA SIDO EL DE TENDER PUENTES ACADEMICOS ENTRE EL IFAL Y ENP, QUE HAN PERMITIDO UN C LIDO DI LOGO ENTRE CULTURAS, LO QUE DESPUES EXTENDIO AL ORFEO CATAL N. ROSA MARIA DUR N GILI HA SABIDO ALIMENTAR CON SENSIBILIDAD E INTELIGENCIA, PARA SI MISMA Y PARA LOS DEM S, UN DI LOGO FECUNDO Y UN ENCUENTRO ENRIQUECEDOR ENTRE LAS CULTURAS MEXICANA Y FRANCESA, INDICO GERARD FONTAINE, DURANTE UNA BREVE RESENA BIOGR FICA DE HOMENAJEADA. LUEGO DEL TRIUNFO DE FRANCO EN ESPANA, SU PADRE, UNA FIGURA REPUBLICANA DE PRIMER PLANO, TUVO QUE EXILIARSE A FRANCIA Y ES ASI COMO ELLA LLEGA A CIUDAD DE MONTPELLIER. POSTERIORMENTE, REALIZO NUEVAMENTE UN VIAJE, ESTA VEZ A UN NUEVO CONTINENTE Y A UNA NUEVA PATRIA: MEXICO. AQUI HA VIVIDO SIN RENUNCIAR A NADA, NI A SU IDENTIDAD CULTURAL, NI A SU CARRERA PROFESIONAL, NI A SU AF N POR DESCUBRIR. EGRESADA DE FACULTAD DE FILOSOFIA Y LETRAS DE UNAM, TIENE UNA ESPECIALIDAD EN DID CTICA DEL FRANCES POR EL IFAL Y SORBONA; SU CURIOSIDAD INTELECTUAL, DESTACO GERARD FONTAINE, HA LLEVADO A PERFECCIONARSE SIN CESAR PARA OFRECER SIEMPRE ALGO M S Y MEJOR A SUS ALUMNOS Y COLEGAS. ES PROFESORA DE FRANCES EN ENP DESDE 1960. A PRINCIPIOS DE LOS ANOS SETENTA, FUNDO CON ALGUNOS AMIGOS ASOCIACION DE PROFESORES E INVESTIGADORES DE FRANCES DE QUE HASTA HORA SIGUE SIENDO REFERENCIA Y autorIDAD MORAL. CON SU EJEMPLO, ROSA MARIA DUR N NOS MUESTRA QUE ES POSIBLE SER UNA MUJER PLENA Y PROFESIONISTA, EN PALABRAS DE SU HERMANO, EL PROFESOR MANUEL DUR N. EN CEREMONIA SE CONDECORO TAMBIEN CON LAS PALMAS ACADEMICAS A NICOLE LAFOREST MARS, PROFESORA DEL COLEGIO DE CIENCIAS Y HUMANIDADES.
The role of high mobility group box 1 (HMGB-1) in the diabetic retinopathy inflammation and apoptosis. (2015)

Diabetic Retinopathy (DR) is one of the most common complications of the late phase diabetes, and also a common cause of blindness. High mobility group box 1 (HMGB-1) is considered to be an inflammatory mediator in the late phase that promotes inflammation and neovascularization in diabetes. Therefore, this paper discussed the role of HMGB-1 in diabetic retinopathy inflammation and neovascularization. 96 adult SD rats were randomly divided into control and diabetes group. The diabetic rat model was established by intraperitoneal injection of streptomycin (0.1 mol/L). Western blot was applied to determine HMGB-1 and its receptor RAGE and TLR2 protein expression in the serum. TUNEL was used to detect retinal apoptosis. Immunofluorescence was performed to test HMGB1 protein expression in retina. HBGM-1 and RAGE expression in diabetic rat retina was significantly higher than the control (P < 0.05), while TLR2 expression was lower (P < 0.05). TUNEL detection showed that diabetic rat retinal cells presented obviously higher apoptosis rate (P < 0.05). Immunofluorescence test revealed that HMGB1 largely expressed in the diabetic rat retinal cells (P < 0.05). HMGB1 may involve in the pathogenesis of diabetic retinopathy by binding with RAGE receptor to accelerate rat retinal cells apoptosis.
Ten myths of multimodal interaction (1999)

article Free Access Share on Ten myths of multimodal interaction Author: Sharon Oviatt Oregon Graduate Institute of Science and Technology, Beaverton Oregon Graduate Institute of Science and Technology, BeavertonView Profile Authors Info & Claims Communications of the ACMVolume 42Issue 11Nov. 1999pp 74–81https://doi.org/10.1145/319382.319398Published:01 November 1999Publication History 372citation8,275DownloadsMetricsTotal Citations372Total Downloads8,275Last 12 Months374Last 6 weeks43 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteView all FormatsPDF
In Vitro Development of Reconstructed Porcine Oocytes after Somatic Cell Nuclear Transfer1 (2000)

This study was designed to examine the developmental ability of porcine embryos after somatic cell nuclear transfer. Porcine fibroblasts were isolated from fetuses at Day 40 of gestation. In vitro-matured porcine oocytes were enucleated and electrically fused with somatic cells. The reconstructed eggs were activated using electrical stimulus and cultured in vitro for 6 days. Nuclear-transferred (NT) embryos activated at a field strength of 120 V/mm (11.6 +/- 1.6%) showed a higher developmental rate as compared to the 150-V/mm group (6.5 +/- 2.3%) (P: < 0.05), but the mean cell numbers of blastocysts were similar between the two groups. Rates of blastocyst development from NT embryos electrically pulsed at different times (2, 4, and 6 h) after electrofusion were 11.6 +/- 2.9, 6.6 +/- 2.3, and 8.1 +/- 3.3%, respectively. The mean cell numbers of blastocysts developed from NT embryos were gradually decreased (30.4 +/- 10.4 > 24.6 +/- 10.1 > 16.5 +/- 7.4 per blastocyst) as exposure time (2, 4, and 6 h) of nuclei to oocyte cytoplast before activation was prolonged. There was a significant difference in the cell number between the 2- and 6-h groups (P: < 0. 05). Nuclear-transferred embryos (9.4 +/- 0.9%) had a lower developmental rate than in vitro fertilization (IVF)-derived (21.4 +/- 1.9%) or parthenogenetic embryos (22.4 +/- 7.2%) (P: < 0.01). The mean cell number (28.9 +/- 11.4) of NT-derived blastocysts was smaller than that (38.6 +/- 10.4) of IVF-derived blastocysts (P: < 0. 05) and was similar to that (29.9 +/- 12.1) of parthenogenetic embryos. Our results suggest that porcine NT eggs using somatic cells after electrical activation have developmental potential to the blastocyst stage, although with smaller cell numbers compared to IVF embryos.
A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H‐2b mice: Fine specificity and T cell receptor Vβ expression of encephalitogenic T cells (1995)

A predominant response to myelin oligodendrocyte glycoprotein (MOG) was recently observed in patients with multiple sclerosis (MS). To study the possible pathogenic role of T cell response to MOG in MS, we have investigated the encephalitogenic potential of MOG. Synthetic MOG peptides, pMOG 1-21, 35-55, 67-87, 104-117 and 202-218, representing predicted T cell epitopes, were injected into C57BL/6J and C3H.SW (H-2b) mice. The mice developed significant specific T cell responses to pMOG 1-21, pMOG 35-55 and pMOG 104-117. However, pMOG 35-55 was the only MOG peptide which could induce neurological impairment. The highly reproducible disease was chronic, with ascending paralysis and neuropathology comparable with those observed in experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein or proteolipid protein, except that in H-2b mice the disease was consistently non-remitting. These features differ markedly from those which we recently observed in PL (H-2u) mice with pMOG 35-55-induced disease. In PL mice, pMOG 35-55-induces atypical chronic relapsing EAE, the expression and progression of which are unpredictable. Hence, in different mouse strains, the same MOG peptide can induce typical EAE characterized by ascending paralysis, or atypical EAE with unpredictable clinical signs. pMOG 35-55-specific T cells from H-2b mice recognized an epitope within amino acids 40-55 of the MOG molecule, and pMOG 40-55-reactive T cell lines were encephalitogenic upon transfer into syngeneic recipients. The encephalitogenic pMOG 35-55-reactive C57BL/6J T cell lines expressed V beta 1, V beta 6, V beta 8, V beta 14 and V beta 15 gene segments, and the pMOG 35-55-reactive C3H.SW T cell lines expressed V beta 1, V beta 2, V beta 6, V beta 8, V beta 10, V beta 14, and V beta 15 gene segments. However, in both mouse strains, the utilization of the V beta 8 gene product was predominant (40-43%). The highly reproducible encephalitogenic activity of pMOG 35-55 strongly suggests a pathogenic role for T cell reactivity to MOG in MS and supports the possibility that MOG may also be a primary target antigen in the disease.
Optimum phase-acquisition technique for charge-pump PLL (1997)

In this paper, we propose a new optimum phase-acquisition algorithm controlling the loop gain of a charge-pump PLL (CP-PLL) in the sense of the MMSE criterion. A set of recursive difference equations minimizing RMS jitter of output phase is derived to obtain an optimum gear-shifting sequence with a zero-phase start (ZPS) assumption. It is shown that the optimum gear-shifting sequence is independent of the variance of the input phase jitter. A procedure for applying this sequence to the design of CP-PLL circuits is described, Both behavoral simulation and HSPICE circuit-level simulation demonstrate that the proposed design leads to an efficient CP-PLL having both fast acquisition and significant jitter reduction characteristics. The optimal gear-shifting CP-PLL outperforms the conventional CP-PLLs. These methods can be used for clock recovery applications such as data communication receivers, disk drive read/write channels, and local area networks, as well as for other applications requiring very short initial preamble periods.
Differential Expression of the Arabidopsis Cytochrome c Genes Cytc-1 and Cytc-2. Evidence for the Involvement of TCP-Domain Protein-Binding Elements in Anther- and Meristem-Specific Expression of the Cytc-1 Gene (2005)

The promoters of the Arabidopsis (Arabidopsis thaliana) cytochrome c genes, Cytc-1 and Cytc-2, were analyzed using plants transformed with fusions to the beta-glucuronidase coding sequence. Histochemical staining of plants indicated that the Cytc-1 promoter directs preferential expression in root and shoot meristems and in anthers. In turn, plants transformed with the Cytc-2 promoter fusions showed preferential expression in vascular tissues of cotyledons, leaves, roots, and hypocotyls, and also in anthers. Quantitative measurements in extracts prepared from different organs suggested that expression of Cytc-1 is higher in flowers, while that of Cytc-2 is higher in leaves. The analysis of a set of deletions and site-directed mutants of the Cytc-1 promoter indicated that a segment located between -147 and -156 from the translation start site is required for expression and that site II elements (TGGGCC/T) located in this region, coupled with a downstream internal telomeric repeat (AAACCCTAA), are responsible for the expression pattern of this gene. Proteins present in cauliflower nuclear extracts, as well as a recombinant protein from the TCP-domain family, were able to specifically bind to the region required for expression. We propose that expression of the Cytc-1 gene is linked to cell proliferation through the elements described above. The fact that closely located site II motifs are present in similar locations in several genes encoding proteins involved in cytochrome c-dependent respiration suggests that these elements may be the target of factors that coordinate the expression of nuclear genes encoding components of this part of the mitochondrial respiratory chain.
Widespread tissue distribution of aminopeptidase A, an evolutionarily conserved ectoenzyme recognized by the BP‐1 antibody (1993)

Early B-lineage cells in mice express a cell surface glycoprotein, recognized by the BP-1 and 6C3 monoclonal antibodies, that has been identified as aminopeptidase A (APA E.C.3.4.11.7). In the present studies we obtained evidence by DNA "zoo-blot" analysis that the APA gene is highly conserved. This ectoenzyme catalyzes the removal of N-terminal Glu- and Asp-residues to convert angiotensin II to angiotensin III, a degradation step important in local regulation of blood pressure in mammals. To gain further insight into the physiology of this molecule, which is shared between immune and vascular systems, we examined the tissue distribution of BP-1 mRNA using a cDNA probe and of the protein antigen using the BP-1 antibody for immunohistology. APA transcripts were present in all tissues examined. Abundant BP-1/APA was found in the intestinal brush border of the small intestine, renal glomeruli, proximal renal tubules, pulmonary alveolar walls and vascular endothelium in many organs. Other tissues containing the BP-1 antigen included stromal cells in the thymus cortex, bile canaliculi in liver, gall bladder epithelium, interlobular ducts in pancreas, the ovarian theca interna, basement membrane of the epididymis and the splanchnopleure in placenta. APA enzyme activities have been identified in most of these locations, in keeping with identification of the BP-1/6C3 antigen as APA. The data suggest this ectopeptidase may serve diverse physiologic roles in a broad spectrum of tissues.
Lithiation of methoxypyridines directed by .alpha.-amino alkoxides (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLithiation of methoxypyridines directed by .alpha.-amino alkoxidesDaniel L. Comins and Michael O. KillpackCite this: J. Org. Chem. 1990, 55, 1, 69–73Publication Date (Print):January 1, 1990Publication History Published online1 May 2002Published inissue 1 January 1990https://pubs.acs.org/doi/10.1021/jo00288a014https://doi.org/10.1021/jo00288a014research-articleACS PublicationsRequest reuse permissionsArticle Views2173Altmetric-Citations74LEARN 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
Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells (2014)

Sequence-specific nucleases such as TALEN and the CRISPR/Cas9 system have so far been used to disrupt, correct or insert transgenes at precise locations in mammalian genomes. We demonstrate efficient 'knock-in' targeted replacement of multi-kilobase genes in human induced pluripotent stem cells (iPSC). Using a model system replacing endogenous human genes with their mouse counterpart, we performed a comprehensive study of targeting vector design parameters for homologous recombination. A 2.7 kilobase (kb) homozygous gene replacement was achieved in up to 11% of iPSC without selection. The optimal homology arm length was around 2 kb, with homology length being especially critical on the arm not adjacent to the cut site. Homologous sequence inside the cut sites was detrimental to targeting efficiency, consistent with a synthesis-dependent strand annealing (SDSA) mechanism. Using two nuclease sites, we observed a high degree of gene excisions and inversions, which sometimes occurred more frequently than indel mutations. While homozygous deletions of 86 kb were achieved with up to 8% frequency, deletion frequencies were not solely a function of nuclease activity and deletion size. Our results analyzing the optimal parameters for targeting vector design will inform future gene targeting efforts involving multi-kilobase gene segments, particularly in human iPSC.