gebhart/patrepeval huggingface dataset:
Plasma Cell Development in Synovial Germinal Centers in Patients with Rheumatoid and Reactive Arthritis (1999)

Plasma cells are found surrounding the inflammatory infiltrates of macrophages, T, and B cells in the synovial tissue of patients with rheumatoid and reactive arthritis. This characteristic arrangement suggests that in the synovial tissue CD20+ B cells differentiate into plasma cells. To examine clonal relationships, we have used micromanipulation to separately isolate CD20+ B cells and plasma cells from single infiltrates. DNA was extracted, and from both populations the VH/VL gene repertoires was determined. The data show that in the inflamed synovial tissue activated B cells are clonally expanded. During proliferation in the network of follicular dendritic cells, V gene variants are generated by the hypermutation mechanism. Surprisingly, we do not find identical rearrangements between CD20+ B cells and plasma cells. Nevertheless, the finding of clonally related plasma cells within single infiltrates suggests that these cells underwent terminal differentiation in the synovial tissue. These results indicate that B cell differentiation in the synovial tissue is a dynamic process. Whereas CD20+ B cells may turnover rapidly, plasma cells may well be long lived and thus accumulate in the synovial tissue. The analysis of individual B cells recovered from synovial tissue opens a new way to determine the specificity of those cells that take part in the local immune reaction. This will provide new insights into the pathogenesis of chronic inflammatory diseases like rheumatoid or reactive arthritis.
Effect of the amine non‐leaving group on the structure and stability of DNA complexes with cis‐[Pt(R‐NH2)2(NO3)2] (1991)

The antitumor compound cis-[Pt(NH3)2Cl2] (cisplatin), conserves two ammine ligands during the reaction with its cellular target DNA. Modifications of these non-leaving groups change the antineoplastic properties of this compound and its genotoxic effects. It is therefore of interest to determine the influence of non-leaving groups on the structure and stability of DNA in vitro. We have investigated platinum-DNA adducts formed by cis-[Pt(R-NH2)2(NO3)2] (where R-NH2 = NH3, methylamine, cyclobutylamine, cyclopentylamine and cyclohexylamine) as a function of DNA binding. All compounds quantitatively reacted with DNA in less than 1 h at 37 degrees C. They formed bifunctional adducts with adjacent nucleotides judging from the displacement of the intercalating molecule ethidium bromide, ultraviolet absorption spectroscopy and circular dichroism. Substitution of a H on the NH3 ligand by alkyl groups dramatically destabilized the platinum-DNA complex. Thermal stability decreased progressively with an increasing number of carbon atoms, delta tm = -4.4 degrees C for 3 cyclohexylamine-platinum-DNA adducts/1000 nucleotides, conditions where cisplatin had no effect. DNA adducts with cyclobutylamine and cyclohexylamine ligands inhibited the hydrolysis of platinum-DNA complexes by S1 nuclease. Km for the digestion of DNA containing these lesions was 2.3 times greater than for cisplatin, indicating steric inhibition of enzyme-substrate complex formation. These results show that the non-leaving groups of substituted cis-Pt(II) compounds may destabilize DNA and interfere with protein-DNA interactions. These perturbations may have consequences for the genotoxic and antitumor activities of platinum compounds.
Regulation of blood pressure by the type 1A angiotensin II receptor gene. (1995)

The renin-angiotensin system plays a critical role in sodium and fluid homeostasis. Genetic or acquired alterations in the expression of components of this system are strongly implicated in the pathogenesis of hypertension. To specifically examine the physiological and genetic functions of the type 1A receptor for angiotensin II, we have disrupted the mouse gene encoding this receptor in embryonic stem cells by gene targeting. Agtr1A(-/-) mice were born in expected numbers, and the histomorphology of their kidneys, heart, and vasculature was normal. AT1 receptor-specific angiotensin II binding was not detected in the kidneys of homozygous Agtr1A(-/-) mutant animals, and Agtr1A(+/-) heterozygotes exhibited a reduction in renal AT1 receptor-specific binding to approximately 50% of wild-type [Agtr1A(+/+)] levels. Pressor responses to infused angiotensin II were virtually absent in Agtr1A(-/-) mice and were qualitatively altered in Agtr1A(+/-) heterozygotes. Compared with wild-type controls, systolic blood pressure measured by tail cuff sphygmomanometer was reduced by 12 mmHg (1 mmHg = 133 Pa) in Agtr1A(+/-) mice and by 24 mmHg in Agtr1A(-/-) mice. Similar differences in blood pressure between the groups were seen when intraarterial pressures were measured by carotid cannulation. These studies demonstrate that type 1A angiotensin II receptor function is required for vascular and hemodynamic responses to angiotensin II and that altered expression of the Agtr1A gene has marked effects on blood pressures.
A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF- B and enhanced IRF-3/STAT1 activation) (2005)

To identify the molecular basis underlying the functions of tumor-associated macrophages (TAMs), we characterized the gene expression profile of TAMs isolated from a murine fibrosarcoma in comparison with peritoneal macrophages (PECs) and myeloid suppressor cells (MSCs), using a cDNA microarray technology. Among the differentially expressed genes, 15 genes relevant to inflammation and immunity were validated by real-time polymerase chain reaction (PCR) and protein production. Resting TAMs showed a characteristic gene expression pattern with higher expression of genes coding for the immunosuppressive cytokine IL-10, phagocytosis-related receptors/molecules (Msr2 and C1q), and inflammatory chemokines (CCL2 and CCL5) as expected, as well as, unexpectedly, IFN-inducible chemokines (CXCL9, CXCL10, CXCL16). Immunohistology confirmed and extended the in vitro analysis by showing that TAMs express M2-associated molecules (eg, IL-10 and MGL1), as well as CCL2, CCL5, CXCL9, CXCL10, and CXCL16, but no appreciable NOS2. Lipopolysaccharide (LPS)-mediated activation of TAMs resulted in defective expression of several proinflammatory cytokines (eg, IL-1beta, IL-6, TNF-alpha) and chemokines (eg, CCL3), as opposed to a strong up-regulation of immunosuppressive cytokines (IL-10, TGFbeta) and IFN-inducible chemokines (CCL5, CXCL9, CXCL10, CXCL16). Thus, profiling of TAMs from a murine sarcoma revealed unexpected expression of IFN-inducible chemokines, associated with an M2 phenotype (IL-10high, IL-12low), and divergent regulation of the NF-kappaB versus the IRF-3/STAT1 pathway.
A Survey of Position Trackers (1992)

This paper is a survey of position-tracking technologies and their use in virtual reality (VR) applications. A framework is established to evaluate the suitability of a position-tracking implementation for virtual reality use. Mechanical, optical, magnetic, and acoustic implementations are discussed with examples of each. Also, the effect of position tracking on a virtual reality user is discussed, especially with regard to the position tracker's role as a cause of simulation sickness. A catalog of implementations and uses is included in an appendix.
Expression of Amino-Terminal Portions or Full-Length Viral Replicase Genes in Transgenic Plants Confers Resistance to Potato Virus X Infection. (1992)

The first open reading frame (ORF 1) of potato virus X (PVX) encodes a putative replicase gene. Transgenic tobacco lines expressing ORF 1 are resistant to PVX infection when inoculated with either PVX or PVX RNA. Analyses of lines containing various portions of the ORF 1 gene demonstrated that resistance is conferred to plants by expressing approximately the first half of the ORF 1 gene. One line expressing the untranslated leader and first 674 codons of ORF 1 is highly resistant to PVX infection. Conversely, lines expressing either approximately the third or fourth quarter of the ORF 1 gene, which contain the conserved nucleotide triphosphate (NTP) binding motif and Gly-Asp-Asp (GDD) motif, respectively, are not protected from PVX infection. In the resistant full-length and amino-terminal lines, lower numbers of local lesions were observed, and the virus accumulation in the inoculated and upper leaves was reduced when compared with the nontransformed control. When the performance of the most resistant ORF 1 line was compared with the most resistant coat protein (CP) line in a resistance test, the best ORF 1 line was more resistant to PVX infection than the best transgenic line expressing the PVX CP gene. These findings define a promising new approach for controlling plant viral infection.
Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell targeting of mutant Kras in transgenic mice. (2003)

Activating mutation of the Kras oncogene is the most frequent and perhaps the earliest genetic alteration associated with pancreatic cancer. To examine the link between mutant Kras and exocrine pancreatic cancer, we generated transgenic mice carrying an elastase-mutant Kras transgene, which targets expression to pancreatic acinar cells. Most elastase-Kras founder mice displayed perinatal pancreatic acinar cell hyperplasia and dysplasia. However, adult mice in two surviving lineages displayed preinvasive pancreatic neoplastic lesions with ductal morphology, thereby providing a unique mouse model in which lesion histotype and initiating genetic alteration overlap with the human disease. Our findings suggest that Kras mutation is associated with development of early stage duct-like lesions in pancreas, but that additional alterations must accompany progression to malignancy.
Pathologic assessment of the vulnerable human coronary plaque (2004)

Despite significant strides towards an understanding of the initiation and progression of atherosclerosis and the influence of risk factors, coronary heart disease remains the principal killer in the western world.1 If progress in the field is to continue in the 21st century, one must focus on high risk patients with lesions that are vulnerable to thrombosis together with the triggering mechanisms that cause plaques to rupture at a precise location and time. Although animal studies have helped define the molecular mechanisms of atherosclerosis, a convincing model of plaque rupture still does not exist. Therefore, the development of future treatments targeted against plaque instability is contingent upon our ability to confidently recognise precursor lesions likely to thrombose; this will be primarily achieved via improved imaging modalities.

Insights into the mechanisms of coronary thrombosis extend from detailed analyses of underlying plaque morphologies in necropsy specimens from sudden death victims.2,3 In 50–75% of these cases, the culprit lesion (fatal plaque) shows a coronary thrombus whereas the remainder without thrombi exhibit stable coronary plaques with > 75% cross sectional area luminal narrowing.4 The major cause of acute coronary thrombosis is plaque rupture, and the precursor lesion has been termed vulnerable plaque (fig 1) or, as defined by our laboratory, the thin cap fibroatheroma (TCFA). In this review, we will critically analyse the pathology of plaque rupture with emphasis on its relation to TCFAs and healed plaque ruptures to gain a better understanding of the lesion most responsible for coronary morbidity and mortality.



 Figure 1 
 A non-haemodynamically limiting thin cap fibroatheroma. (A) Low power view of a thin cap fibroatheroma (TCFA) with a relatively large eccentric necrotic core (NC) and an overlying thin fibrous cap (< 65 μm); the greyish material in the lumen is barium gelatin (Movat pentachrome, ×20). (B) Image of …
The Mitochondrial Carrier Family of Transport Proteins: Structural, Functional, and Evolutionary Relationships (1993)

Energy transduction in mitochondria requires the transport of many specific metabolites across the inner membrane of this eukaryotic organelle. We have screened the protein sequence database for proteins homologous to the mitochondrial ATP/ADP exchange carrier, and the homologous proteins found were similarly screened to ensure that all currently sequenced members of the mitochondrial carrier family (MCF) had been identified. Thirty-seven proteins were identified, 28 of which were less than 90% identical to any other sequenced member of the MCF, and the latter proteins fell into 10 clusters or subfamilies as follows: (1) ATP/ADP exchangers of mammals, plants, algae, yeast, and fungi (11 members); (2) a bovine oxoglutarate/malate exchanger (one member); (3) mammalian uncoupling carriers (five members); (4) yeast and mammalian phosphate carriers (three members); (5) MRS proteins that suppress mitochondrial splicing defects in Saccharomyces cerevisiae (two members); (6) a putative peroxysomal carrier of Candida boidinii; (7) a putative solute carrier from the protozoan, Oxytricha fallax; (8) a putative solute carrier from S. cerevisiae; (9) a putative solute carrier from Zea mays, and (10) two putative solute carriers from the mammalian thyroid gland. The specificities of proteins in clusters 5 to 10 are not known. A multiple alignment and an evolutionary tree of the 28 selected members of the MCF were constructed, thus defining the conserved residues and the phylogenetic relationships of the proteins. Hydropathy plots of the homologous regions were determined and averaged, and the average hydropathy plots were evaluated for sequence similarity. These analyses revealed that the six transmembrane spanners exhibited varying degrees of sequence conservation and hydrophilicity. These spanners, and immediately adjacent hydrophilic loop regions, were more highly conserved than other regions of these proteins. All members of the MCF appear to consist of a tripartite structure with each of the three repeated segments being about 100 residues in length. Each repeat contains two transmembrane spanners, the first being more hydrophobic with conserved glycyl and prolyl residues, the second, preceded by a highly conserved glycyl residue, being more hydrophilic with largely conserved hydrophilic residues in certain positions. Five of the six spanners are followed by the largely conserved sequence (D/E)-Hy (K/R)[- = any residue; Hy = a hydrophobic residue]. Based on both intracluster and intercluster statistical comparisons, repeats 1, 2, and 3 are homologous, but repeats 1 are more similar to each other than they are to repeats 2 or 3 or repeats 2 or 3 are to each other.(ABSTRACT TRUNCATED AT 400 WORDS)
Concordant activity of transgene expression cassettes inserted into E1, E3 and E4 cloning sites in the adenovirus genome (2009)

The expression level of a given transgene in an adenoviral vector genome can be accurately and quantitatively inferred from the expression of a marker protein encoded by a second transgene inserted elsewhere in the vector genome.
Identification of bacteria using mass spectrometry (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIdentification of bacteria using mass spectrometryJohn P. Anhalt and Catherine. FenselauCite this: Anal. Chem. 1975, 47, 2, 219–225Publication Date (Print):February 1, 1975Publication History Published online1 May 2002Published inissue 1 February 1975https://doi.org/10.1021/ac60352a007Request reuse permissionsArticle Views2133Altmetric-Citations369LEARN 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 (710 KB) Get e-Alertsclose Get e-Alerts
“Near miss” death in obstructive sleep apnea (1991)

Patients with obstructive sleep apnea who have concomitant chronic obstructive pulmonary disease or hypercarbia and hypoxemia are more prone to develop severe respiratory failure and probable death than those patients with apnea alone. The current study shows that recurrent respiratory failure and presumably mortality from this acute complication can be reversed with effective treatment of the obstructive apnea.
Differential Attraction of Malaria Mosquitoes to Volatile Blends Produced by Human Skin Bacteria (2010)

The malaria mosquito Anopheles gambiae sensu stricto is mainly guided by human odour components to find its blood host. Skin bacteria play an important role in the production of human body odour and when grown in vitro, skin bacteria produce volatiles that are attractive to A. gambiae. The role of single skin bacterial species in the production of volatiles that mediate the host-seeking behaviour of mosquitoes has remained largely unknown and is the subject of the present study. Headspace samples were taken to identify volatiles that mediate this behaviour. These volatiles could be used as mosquito attractants or repellents. Five commonly occurring species of skin bacteria were tested in an olfactometer for the production of volatiles that attract A. gambiae. Odour blends produced by some bacterial species were more attractive than blends produced by other species. In contrast to odours from the other bacterial species tested, odours produced by Pseudomonas aeruginosa were not attractive to A. gambiae. Headspace analysis of bacterial volatiles in combination with behavioural assays led to the identification of six compounds that elicited a behavioural effect in A. gambiae. Our results provide, to our knowledge, the first evidence for a role of selected bacterial species, common on the human skin, in determining the attractiveness of humans to malaria mosquitoes. This information will be used in the further development of a blend of semiochemicals for the manipulation of mosquito behaviour.
Complete nucleotide sequence of the Actinomyces viscosus T14V sialidase gene: presence of a conserved repeating sequence among strains of Actinomyces spp (1993)

The nucleotide sequence of the Actinomyces viscosus T14V sialidase gene (nanH) and flanking regions was determined. An open reading frame of 2,703 nucleotides that encodes a predominately hydrophobic protein of 901 amino acids (M(r), 92,871) was identified. The amino acid sequence at the amino terminus of the predicted protein exhibited properties characteristic of a typical leader peptide. Five 12-amino-acid units that shared between 33 and 67% sequence identity were noted within the central domain of the protein. Each unit contained the sequence Ser-X-Asp-X-Gly-X-Thr-Trp, which is conserved among other bacterial and trypanosoma sp. sialidases. Thus, the A. viscosus T14V nanH gene and the other prokaryotic and eukaryotic sialidase genes evolved from a common ancestor. Southern hybridization analyses under conditions of high stringency revealed the existence of DNA sequences homologous to A. viscosus T14V nanH in the genomes of 18 strains of five Actinomyces species that expressed various levels of sialidase activity. The data demonstrate that the sialidase genes from divergent groups of Actinomyces spp. are highly conserved.
A Kinetic Test Characterizes Kinase Intramolecular and Intermolecular Autophosphorylation Mechanisms (2013)

Many protein kinases catalyze their own activation by autophosphorylation. The mechanism of this is generally considered to be intermolecular and similar to that used in substrate phosphorylation. We derived the kinetic signatures of the four simplest autophosphorylation reactions and developed a test to determine the autoactivation mechanism of individual kinases. Whereas autophosphorylation of Nek7 and Plk4 occurred through an intermolecular mechanism, the kinases Aurora-A and Chk2 followed an intramolecular mechanism. Autophosphorylation of Aurora-A was accelerated in the presence of its protein activator TPX2. Nek9, the binding partner for Nek7, had a concentration-dependent effect such that low amounts enhanced autoactivation of Nek7 and high amounts were inhibitory. A structural model of Aurora-A undergoing autophosphorylation confirmed that an intramolecular mechanism is physically possible, and provided an explanation for how TPX2 could stimulate both autophosphorylation and substrate phosphorylation. The distinct mechanisms of autoactivation have consequences for cellular regulation because each molecule of a kinase that undergoes intramolecular autophosphorylation is activated individually, whereas the activity of kinases that undergo intermolecular autophosphorylation can be rapidly self-amplified in the cell. Local control of individual molecules, such as Aurora-A, may be particularly advantageous for a kinase with multiple, distinct cellular roles.
Effects of Pemafibrate, a Novel Selective PPARα Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial (2018)

Pemafibrate significantly ameliorated lipid abnormalities and was well tolerated in patients with type 2 diabetes comorbid with hypertriglyceridemia.
Identification of early molecular markers for breast cancer (2011)

By comparing murine markers for the ductal carcinoma in situ (DCIS) of the mammary gland with genes up-regulated in human DCIS-samples we were able to identify a set of genes which might allow early detection of DCIS and invasive carcinomas in the future. The similarities between gene expression in DCIS and invasive carcinomas in our data suggest that the early detection and treatment of DCIS is of utmost relevance for the survival of patients who are at high risk of developing breast carcinomas.
Genetic engineering of T-cell receptors: TCR takes to titin (2013)

In this issue of Blood, Linette et al report a cautionary tale—a lethal off-target toxicity following T-cell receptor (TCR) optimization to enhance affinity against a tumor-associated antigen, MAGE-A3.
Bioreversible Protection of Nucleoside Diphosphates (2008)

Going incognito: A new prodrug approach has been developed to facilitate the diffusion of highly polar polyphosphorylated nucleosides across cell membranes (see scheme). Inside the cell, the masking groups on the nucleoside diphosphate should be cleaved rapidly by enzymes to release the antiviral active cargo.