gebhart/patrepeval huggingface dataset:
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency (2015)

This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. (Funded by Johns Hopkins University and others; ClinicalTrials.gov number, NCT01876511.).
Characterization and Comparison of ‘Standard’ and ‘Young’ Tumour‐Infiltrating Lymphocytes for Adoptive Cell Therapy at a Danish Translational Research Institution (2011)

Adoptive cell therapy (ACT) with ex vivo expanded tumour-infiltrating lymphocytes (TILs) in combination with IL-2 is an effective treatment for metastatic melanoma. Modified protocols of cell expansion may allow the treatment of most enrolled patients and improve the efficacy of adoptively transferred cells. The aims of this study were to establish and validate the novel 'Young TIL' method at our institution and perform a head-to-head comparison of clinical-grade products generated with this protocol opposed to the conventional 'Standard TIL', which we are currently using in a pilot ACT trial for patients with melanoma. Our results confirm that 'Young TILs' display an earlier differentiation state, with higher CD27 and lower CD56 expression. In addition, CD8(+) TILs expressing CD27 had longer telomeres compared with the CD27(-). A recently described subset of NK cells, endowed with a high expression of CD56 (CD56(bright)), was detected for the first time in both types of cultures but at a higher frequency on Young TILs. Young and Standard TILs' reactivity against autologous tumours was similar, with significant expression of TNF-α/IFN-γ/CD107a by CD8(+) TILs detected in all cultures analysed. However, either slow expansion with high-dose IL-2 only or large numerical expansion with a rapid expansion protocol, which is required for current therapeutic protocols, significantly modified TIL phenotype by reducing the frequency of less differentiated, cancer-specific TILs. These studies further support the adoption of the Young TIL method in our current ACT trial and highlight the importance of continuous quality control of expansion protocols.
Cell-type-specific signatures of microRNAs on target mRNA expression (2006)

Although it is known that the human genome contains hundreds of microRNA (miRNA) genes and that each miRNA can regulate a large number of mRNA targets, the overall effect of miRNAs on mRNA tissue profiles has not been systematically elucidated. Here, we show that predicted human mRNA targets of several highly tissue-specific miRNAs are typically expressed in the same tissue as the miRNA but at significantly lower levels than in tissues where the miRNA is not present. Conversely, highly expressed genes are often enriched in mRNAs that do not have the recognition motifs for the miRNAs expressed in these tissues. Together, our data support the hypothesis that miRNA expression broadly contributes to tissue specificity of mRNA expression in many human tissues. Based on these insights, we apply a computational tool to directly correlate 3' UTR motifs with changes in mRNA levels upon miRNA overexpression or knockdown. We show that this tool can identify functionally important 3' UTR motifs without cross-species comparison.
Expression of chemokines in the CSF and correlation with clinical disease activity in patients with multiple sclerosis. (2002)

Increased CXCL10 and decreased CCL2 concentrations in the CSF are associated with relapses in MS. Although serial values from individual patients were not available, this study suggests that CXCL10 and CCL2 may return towards baseline concentrations after a relapse. Correlation of CXCL10 with CD4(+) T cell expression of CXCR3 was consistent with its chemoattractant role for activated lymphocytes. Thus CXCL10 neutralising agents and CXCR3 receptor antagonists may be therapeutic targets in MS.
Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q10. (1985)

Coenzyme Q10 (CoQ10), a biochemically established redox component of respiration including the coupled mechanisms of electron transfer and oxidative phosphorylation, is naturally present in the human myocardium. A double-blind and double-crossover trial has been conducted by administering CoQ10 and a matching placebo orally to two groups of patients having class III or IV cardiomyopathy (classification according to criteria of the New York Heart Association). Group A received CoQ10 and then placebo; group B received placebo and then CoQ10. Blood levels of CoQ10 and cardiac function were determined at 0 and 4 weeks (control stabilization period) and at 16 and 28 weeks (after the 12-week CoQ/placebo-treatment periods). For group A, significant increases in CoQ10 blood levels and cardiac function occurred during CoQ10 treatment and then decreased during crossover to placebo. For group B, there was no change in CoQ10 blood levels and cardiac function during placebo treatment, but increases in both parameters occurred in crossover to CoQ10. These patients, steadily worsening and expected to die within 2 years under conventional therapy, generally showed an extraordinary clinical improvement, indicating that CoQ10 therapy might extend the lives of such patients. This improvement could be due to correction of a myocardial deficiency of CoQ10 and to enhanced synthesis of CoQ10-requiring enzymes.
Stereoselective synthesis of diacids by the nickel cyanide and phase-transfer-catalyzed carbonylation of alkynols. Novel dependency of product stereochemistry and optimum stirring speed on the nature of the phase-transfer agent (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective synthesis of diacids by the nickel cyanide and phase-transfer-catalyzed carbonylation of alkynols. Novel dependency of product stereochemistry and optimum stirring speed on the nature of the phase-transfer agentNistala. Satyanarayana and Howard. AlperCite this: Organometallics 1991, 10, 3, 804–807Publication Date (Print):March 27, 1991Publication History Published online1 May 2002Published inissue 27 March 1991https://pubs.acs.org/doi/10.1021/om00049a049https://doi.org/10.1021/om00049a049research-articleACS PublicationsRequest reuse permissionsArticle Views188Altmetric-Citations26LEARN 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
Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5 (1999)

The Dlx5 gene encodes a Distal-less-related DNA-binding homeobox protein first expressed during early embryonic development in anterior regions of the mouse embryo. In later developmental stages, it appears in the branchial arches, the otic and olfactory placodes and their derivatives, in restricted brain regions, in all extending appendages and in all developing bones. We have created a null allele of the mouse Dlx5 gene by replacing exons I and II with the E. coli lacZ gene. Heterozygous mice appear normal. Beta-galactosidase activity in Dlx5+/- embryos and newborn animals reproduces the known pattern of expression of the gene. Homozygous mutants die shortly after birth with a swollen abdomen. They present a complex phenotype characterised by craniofacial abnormalities affecting derivatives of the first four branchial arches, severe malformations of the vestibular organ, a delayed ossification of the roof of the skull and abnormal osteogenesis. No obvious defect was observed in the patterning of limbs and other appendages. The defects observed in Dlx5-/- mutant animals suggest multiple and independent roles of this gene in the patterning of the branchial arches, in the morphogenesis of the vestibular organ and in osteoblast differentiation.
Polyketide synthase and non-ribosomal peptide synthetase thioesterase selectivity: logic gate or a victim of fate? (2015)

Type 1, α/β hydrolase-like thioesterase (TE) domains are essential offloading enzymes, releasing covalently bound products from fatty acid, polyketide, and non-ribosomal peptide biosynthetic complexes. The release step can occur by attack of an exogenous nucleophile effecting hydrolysis or transesterification or by an intramolecular O-, N-, or C-nucleophile, effecting macrolactonization, macrolactamization or Claisen-like condensation of the product. Thus in addition to ensuring turnover of the pathway, TEs provide access to increased chemical diversity. We review the diversity, structure, and mechanism of PKS and NRPS TEs and discuss recent works that highlight the role of TEs as potential arbitrators in offloading. In particular, we examine cases where TEs act as logic gates that ask a particular question about the substrate and use this information to determine the substrate's fate. As the TE mechanism occurs via two steps, we analyze both the loading and release steps independently as logic gates. The use of logic gates provides an important perspective when evaluating the evolution of TEs within a pathway, as well as highlighting work towards the goal of predicting TE function in unknown and engineered pathways.
Fertilizing capacity of transgenic and non-transgenic rabbit spermatozoa after heterospermic insemination (2005)

The aim of this study was to evaluate fertilizing capacity of transgenic and non-transgenic rabbits from 3 rabbit breeds (NZW, Californian and Marder) after heterospermic insemination using phenotypic (white, black and white, and blue) and genotypic (transgene – hFVIII gene) markers. Semen from males was used to make pools of 3 males (one of each breed) and to perform heterospermic insemination. Insemination was carried out in hormonally treated young females with about 10 million of spermatozoa per insemination dose (1.0 ml). Although each female was inseminated with approximately the same number of spermatozoa, sperm from one transgenic male (NZW) was dominant, significant difference was observed in the offspring among the males with similar semen quality (53% vs. 30-17%, P<0.01-0.001). Based on our results we can conclude that transgenesis had no effect on fertilizing capacity of transgenic spermatozoa during heterospermic insemination.
Bronchiolitis Obliterans Syndrome in Chemical Workers Producing Diacetyl for Food Flavorings (2007)

Exposure to an agent during diacetyl production appears to be responsible for causing bronchiolitis obliterans syndrome in chemical process operators, consistent with the suspected role of diacetyl in downstream food production.
Human brain n-chimaerin cDNA encodes a novel phorbol ester receptor (1990)

A human brain-specific cDNA encoding n-chimaerin, a protein of predicted molecular mass 34 kDa, has sequence identity with two different proteins: protein kinase C (PKC) at the N-terminus and BCR protein [product of the breakpoint-cluster-region (BCR) gene, involved in Philadelphia chromosome translocation] at the C-terminus [Hall, Monfries, Smith, Lim, Kozma, Ahmed, Vannaisungham, Leung & Lim (1990) J. Mol. Biol. 211, 11-16]. The sequence identity of n-chimaerin with PKC includes the cysteine-rich motif CX2CX13CX2CX7CX7C, and amino acids upstream of the first cysteine residue, but not the kinase domain. This region of PKC has been implicated in the binding of diacylglycerol and phorbol esters in a phospholipid-dependent fashion. Part of this cysteine-rich motif (CX2CX13CX2C) has the potential of forming a 'Zn-finger' structure. Phorbol esters cause a variety of physiological changes and are among the most potent tumour promoters that have been described. PKC is the only known protein target for these compounds. We now report that n-chimaerin cDNA encodes a novel phospholipid-dependent phorbol ester receptor, with the cysteine-rich region being responsible for this activity. This finding has wide implications for previous studies equating phorbol ester binding with the presence of PKC in the brain.
English Interference Loans as a Resource in the Functional Expansion of St. Lucian Creole (1984)

This paper is a study of language contact between French Creole and English on the Caribbean island of St. Lucia. Although much of the discussion is related to grammatical questions, the implications go beyond issues in descriptive linguistics. The nature of English-Creole contact is an important question for St. Lucian education and social life in general, especially given the increased promotion of Creole as a medium of contact between the St. Lucian government and people, and the possibilities of the future use of Creole as a medium of education and literacy. The study gives some evidence that English-Creole contact in St. Lucia is a phenomenon that may provide one of the mechanisms for the use of St. Lucian Creole (SLC) as an official or literary language, as demonstrated by the speech of St. Lucians in official and literary settings. The first part of the paper outlines the material and social history of the island as it relates to the language situation, particularly to forms of English- Creole contact. The second part reviews some models of language contact phenomena developed by linguists in the past several years, and describes some terminology taken from a study of a socially analagous situation on the Atlantic coast of Costa Rica. The third part is a discussion of some material from Creole texts which were recorded in St. Lucia in official or literary settings, and a description of some of the formal aspects of English-Creole contact, specifically English interference loans in Creole discourse. By way of conclusion, the paper discusses problems of language development raised by St. Lucian language planners and educators, as they relate to the phenomena described in the study.
Alternative Granulation Technique: Melt Granulation (1996)

A melt granulation process has been investigated (1, 2) which efficiently agglomerates pharmaceutical powders for use in both immediate- and sustained-release solid dosage forms. The process utilizes materials that are effective as granulating fluids when they are in the molten state. Cooling of the agglomerated powders and the resultant solidification of the molten materials completes the granulation process. Both the molten agglomeration and cooling solidification were accomplished in a high shear Collette Gral mixer equipped with a jacketed bowl. Hence, the melt granulation process replaces the conventional granulation and drying operations which use water or alcohol solutions. The melt granulation process has been investigated using immediate- and sustained-release TAVIST® (clemastine fumarate USP) tablet formulations. The TAVIST granulations have been characterized by power consumption monitoring, measurement of the granulation particle size distribution, bulk and tapped density determinations, and loss-on-drying measurements. Scale-up of the melt granulation process for the sustained release TAVIST tablet formulation was judged successful based on a comparison of the hardness, friability, weight uniformity during compression, disintegration time, and dissolution rate data obtained at different manufacturing scales.
In prostate cancer, low adiponectin levels are not associated with insulin resistance (2015)

In spite of what would have been expected from the relevant literature, our data suggest that the hypoadiponectinaemia in prostatic cancer does not appear to be associated with insulin resistance.
A General Strategy for the Chemoenzymatic Synthesis of Asymmetrically Branched N -Glycans (2013)

A systematic, efficient means of producing diverse libraries of asymmetrically branched N-glycans is needed to investigate the specificities and biology of glycan-binding proteins. To that end, we describe a core pentasaccharide that at potential branching positions is modified by orthogonal protecting groups to allow selective attachment of specific saccharide moieties by chemical glycosylation. The appendages were selected so that the antenna of the resulting deprotected compounds could be selectively extended by glycosyltransferases to give libraries of asymmetrical multi-antennary glycans. The power of the methodology was demonstrated by the preparation of a series of complex oligosaccharides that were printed as microarrays and screened for binding to lectins and influenza-virus hemagglutinins, which showed that recognition is modulated by presentation of minimal epitopes in the context of complex N-glycans.
A Myb-related transcription factor is involved in the phytochrome regulation of an Arabidopsis Lhcb gene. (1997)

We have isolated the gene for a protein designated CCA1. This protein can bind to a region of the promoter of an Arabidopsis light-harvesting chlorophyll a/b protein gene, Lhcb1*3, which is necessary for its regulation by phytochrome. The CCA1 protein interacted with two imperfect repeats in the Lhcb1*3 promoter, AAA/cAATCT, a sequence that is conserved in Lhcb genes. A region near the N terminus of CCA1, which has some homology to the repeated sequence found in the DNA binding domain of Myb proteins, is required for binding to the Lhcb1*3 promoter. Lines of transgenic Arabidopsis plants expressing antisense RNA for CCA1 showed reduced phytochrome induction of the endogenous Lhcb1*3 gene, whereas expression of another phytochrome-regulated gene, rbcS-1A, which encodes the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, was not affected. Thus, the CCA1 protein acts as a specific activator of Lhcb1*3 transcription in response to brief red illumination. The expression of CCA1 RNA was itself transiently increased when etiolated seedlings were transferred to light. We conclude that the CCA1 protein is a key element in the functioning of the phytochrome signal transduction pathway leading to increased transcription of this Lhcb gene in Arabidopsis.
Randomized phase II trial of cisplatin with mitomycin or doxorubicin for malignant mesothelioma by the Cancer and Leukemia Group B. (1993)

Moderate antitumor activity has been observed with both regimens. In this randomized phase II trial, the overall response rates, time to treatment failure, and overall survival appear to be similar for the two regimens tested.
Second Cysteine-rich Domain of Dickkopf-2 Activates Canonical Wnt Signaling Pathway via LRP-6 Independently of Dishevelled (2002)

Recent evidence suggests that members of the Dickkopf (Dkk) family can directly bind to LDL-related protein (LRP)-6, resulting in inhibition of Wnt-activated signaling. To further characterize the interactions between Dkk and LRP proteins, conditioned media containing individually conserved cysteine-rich domains of Dkk-1 and Dkk-2 were prepared. Although full-length Dkk-1 and Dkk-2 and the second cysteine-rich domains of both Dkk molecules inhibited Wnt-3a-induced activation of lymphoid enhancing factor (LEF)-1, a downstream target of the canonical pathway, we found that the second cysteine-rich domain of Dkk-2 (Dkk-2C2) was able to stimulate the canonical pathway when LRP-6 was ectopically expressed in NIH3T3 cells. This effect of Dkk-2C2 could be blocked by a monoclonal antibody specific to the second YWTD repeat domain of LRP-5/6, suggesting that Dkk-2C2 acts via LRP-6. We also showed that while both Axin and the DIX domain of Dishevelled (Dvl) could inhibit Dkk-2C2-induced activation of LEF-1, the DEP domain of Dvl, which inhibited Wnt-induced activation of LEF-1, failed to inhibit the activation of LEF-1 by Dkk-2C2 or by an activated form of LRP-5, LRPC2. In addition, glycogen synthase kinase-3 beta, a potent inhibitor for both Dvl and Wnt, also failed to inhibit LRPC2 or Dkk-2C2. Furthermore, knocking-down the expression of Dvl molecules by short interfering RNAs specific to Dvl inhibited Wnt-induced, but not LRPC2-induced, activation of LEF-1. All the evidence indicates that Dkk-2C2 signals through LRP proteins, which does not require Dvl, while Wnt protein may employ both Dvl, presumably through Fz, and LRP to achieve more efficient signal transduction.
Biochemical and Structural Characterization of the Interaction of Memapsin 2 (β-Secretase) Cytosolic Domain with the VHS Domain of GGA Proteins (2003)

Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease that initiates the hydrolysis of beta-amyloid precursor protein (APP) leading to the production of amyloid-beta and the onset of Alzheimer's disease (AD). Both memapsin 2 and APP are transported from the cell surface to endosomes where APP hydrolysis takes place. Thus, the intracellular transport mechanism of memapsin 2 is important for understanding the pathogenesis of AD. We have previously shown that the cytosolic domain of memapsin 2 contains an acid-cluster-dileucine (ACDL) motif that binds the VHS domain of GGA proteins (He et al. (2002) FEBS Lett. 524, 183-187). This mechanism is the presumed recognition step for the vesicular packaging of memapsin 2 for its transport to endosomes. The phosphorylation of a serine residue within the ACDL motif has been reported to regulate the recycling of memapsin 2 from early endosomes back to the cell surface. Here, we report a study on the memapsin 2/VHS domain interaction. Using isothermal titration calorimetry, the dissociation constant, K(d), values are 4.0 x 10(-4), 4.1 x 10(-4), and 3.1 x 10(-4) M for VHS domains from GGA1, GGA2, and GGA3, respectively. With the serine residue replaced by phosphoserine, the K(d) decreased about 10-, 4-, and 14-fold for the same three VHS domains. A crystal structure of the complex between memapsin 2 phosphoserine peptide and GGA1 VHS was solved at 2.6 A resolution. The side chain of the phosphoserine group does not interact with the VHS domain but forms an ionic interaction with the side chain of the C-terminal lysine of the ligand peptide. Energy calculation of the binding of native and phosphorylated peptides to VHS domains suggests that this intrapeptide ionic bond in solution may reduce the change in binding entropy and thus increase binding affinity.
Fetal Anatomy of the Human Carotid Sheath and Structures In and Around It (2010)

The aim of this study was to find basic rules governing the morphological development of the typical neurovascular sheath. We carried out histological examination of 15 paraffin-embedded mid-term fetuses at 9-25 weeks of gestation (three fetuses each at 9, 12, 15, 20, and 25 weeks). As the result, the vagus nerve showed a high propensity to change its topographical relationship with the common carotid artery (CCA) during 9-20 weeks of gestation: that is, from a primitive ventral course to a final dorsal course. The adventitia of the great arteries, which was distinct from other fascial structures, became evident by 15 weeks. The carotid sheath appeared at and after 20 weeks: it was clearly separated from the prevertebral lamina of the deep cervical fasciae, but fused with the pretracheal lamina covering the strap muscles. Thus the carotid sheath, as well as the topographical relationships of structures within it, seems to become established much later than the prevertebral and pretracheal laminae of the deep cervical fasciae. However, the adventitia of the cervical great arteries consistently becomes evident much earlier than the sheath, and it seems to be regarded as one of the basic components of the fetal deep cervical fasciae.