gebhart/patrepeval huggingface dataset:
Conformational Dependence ofAnaplasma marginaleMajor Surface Protein 5 Surface-Exposed B-Cell Epitopes (1998)

The Anaplasma marginale outer membrane is composed of immunogenic major surface proteins (MSPs) linked both covalently and noncovalently in multimeric complexes (M. C. Vidotto, T. C. McGuire, T. F. McElwain, G. H. Palmer, and D. P. Knowles, Infect. Immun. 62:2940-2946). Consequently, effective induction of antibody against surface-exposed MSP epitopes has been postulated to require maintenance of MSP secondary through quatenary structures. Using MSP5 as a model and the approach of epitope mapping with recombinant expressed full-length and truncated proteins, we demonstrated that the immunodominant surface epitope bound by monoclonal antibody (MAb) ANAF16C1 required disparate amino- and carboxy-terminal regions of MSP5, indicating the conformational dependence of this epitope. The required amino-terminal MSP5 region included the cysteines involved in intramolecular disulfide bonding. The dependence of the immunodominant epitope on disulfide bonding was confirmed by loss of MAb ANAF16C1 binding to MSP5 following disulfide bond reduction and covalent modification of the reduced sulfhydryl groups. The recognition of the MSP5 immunodominant epitope by antibody induced by protective immunization with A. marginale outer membranes was also conformationally dependent, as shown by the loss of epitope binding following serum adsorption with native but not reduced and denatured A. marginale. Importantly, the antibody response to all immunodominant MSP5 surface epitopes was restricted to conformationally dependent epitopes, since the binding of polyclonal anti-MSP5 antibody to the A. marginale surface could be blocked by adsorption with native but not denatured and reduced MSP5. These results confirm the importance of the secondary and tertiary structures of MSP epitopes as immune system targets and support the testing of immunogens which maintain the required conformation.
The iterative time reversal mirror: A solution to self-focusing in the pulse echo mode (1991)

Accurate focusing in an inhomogeneous medium is difficult to implement. In order to focus on a reflective target we have extended the concept of optical phase-conjugate mirrors, valid for monochromatic signals, to broadband pulses such as those used in ultrasound echography. The transducer’s linear response to the acoustic pressure allows one to replace the phase conjugation by a time reversal operation on the pulse echo signals. The time reversal mirror is an array of transmit–receive transducers. A first incident wave is reflected by the target. The received signals are stored in shift registers, reversed in time, and then reemitted. The main advantage of this process is that waves distorted by the propagation through an aberrating medium are corrected by the mirror operation and the back propagation through the medium. When the medium contains several reflectors, this time reversal process can be iterated in order to focus on the most reflective one. We present theoretical results on this principle, numerical simulations, and experimental results with a 1-D array working at a central frequency of 3 MHz.
Tissue-resident macrophages in the intestine are long lived and defined by Tim-4 and CD4 expression (2018)

A defining feature of resident gut macrophages is their high replenishment rate from blood monocytes attributed to tonic commensal stimulation of this site. In contrast, almost all other tissues contain locally maintained macrophage populations, which coexist with monocyte-replenished cells at homeostasis. In this study, we identified three transcriptionally distinct mouse gut macrophage subsets that segregate based on expression of Tim-4 and CD4. Challenging current understanding, Tim-4<sup>+</sup>CD4<sup>+</sup> gut macrophages were found to be locally maintained, while Tim-4<sup>-</sup>CD4<sup>+</sup> macrophages had a slow turnover from blood monocytes; indeed, Tim-4<sup>-</sup>CD4<sup>-</sup> macrophages were the only subset with the high monocyte-replenishment rate currently attributed to gut macrophages. Moreover, all macrophage subpopulations required live microbiota to sustain their numbers, not only those derived from blood monocytes. These findings oppose the prevailing paradigm that all macrophages in the adult mouse gut rapidly turn over from monocytes in a microbiome-dependent manner; instead, these findings supplant it with a model of ontogenetic diversity where locally maintained subsets coexist with rapidly replaced monocyte-derived populations.
Gemcitabine: Single-Agent and Combination Therapy in Non-Small Cell Lung Cancer (1999)

With the advent of several newer agents with single-agent response rates greater than 20% and approximately 30%-40% in combination therapy, non-small cell lung cancer (NSCLC) may now be considered a malignancy that is moderately sensitive to chemotherapy. Examples of these agents include the taxanes, paclitaxel and docetaxel; vinorelbine, a new vinca alkaloid, and the camptothecins, of which CPT-11 is the most actively studied agent. Another new and exciting agent is gemcitabine, a nucleoside analogue structurally related to cytosine arabinoside. Gemcitabine's mechanism of action is activated by deoxycytidine kinase to dFdCMP, dFdCDP and dFdCTP. The latter two compounds, when incorporated into DNA, result in chain termination. Phase I studies using a short infusion schedule given weekly for three weeks followed by one week off established 1,000-1,250 mg/m2/week as the maximum tolerated dose. Single-agent gemcitabine has been extensively studied in patients with chemotherapy-naïve advanced NSCLC with response rates of approximately 20%. Response rates for the combination of gemcitabine plus cisplatin are approximately 28%-54% in phase II trials. Recently, this combination has been studied in randomized phase II and III trials revealing improvements in response rates, time to progression and, in the phase III trial, survival. Current and future studies are evaluating gemcitabine in non-cisplatin combinations (i.e., taxanes).
Late onset Alzheimer’s disease genetics implicates microglial pathways in disease risk (2017)

Alzheimer's disease (AD) is a highly heritable complex disease with no current effective prevention or treatment. The majority of drugs developed for AD focus on the amyloid cascade hypothesis, which implicates Aß plaques as a causal factor in the disease. However, it is possible that other underexplored disease-associated pathways may be more fruitful targets for drug development. Findings from gene network analyses implicate immune networks as being enriched in AD; many of the genes in these networks fall within genomic regions that contain common and rare variants that are associated with increased risk of developing AD. Of these genes, several (including CR1, SPI1, the MS4As, TREM2, ABCA7, CD33, and INPP5D) are expressed by microglia, the resident immune cells of the brain. We summarize the gene network and genetics findings that implicate that these microglial genes are involved in AD, as well as several studies that have looked at the expression and function of these genes in microglia and in the context of AD. We propose that these genes are contributing to AD in a non-Aß-dependent fashion.
Synthesis and Biological Evaluation of Phorbol‐Resiniferatoxin (RTX) Hybrids (2004)

Abstract Phorboid 20‐homovanillates modified on ring C to mimic the constitution and conformation of the ultrapotent vanilloid resiniferatoxin (RTX) and on the AB ring system to suppress the tumour‐promoting potential of the terpenoid core were prepared. Several unexpected reactions were discovered, and the structure‐activity relationships for this class of vanilloid ligands were expanded. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)
Sindicato e partido político em Gramsci (2009)

Apresenta o pensamento de Antonio Gramsci como reflexões que permitem à classe trabalhadora se conscientizar como classe, e nessa perspectiva possa articular os diversos instrumentos de luta contra a lógica do capital, principalmente através do Partido Político. É possível que os trabalhadores valorizem toda e qualquer forma de organização e de luta, dentre eles os sindicatos, e os potencializem para a construção de uma nova sociedade, além do capital. Assim, Gramsci tece uma série de críticas aos sindicatos, mostrando suas potencialidades e limites contra a ordem do capital, permitindo-nos perceber que é preciso um instrumento de luta, que ajude a classe trabalhadora a se organizar, a se mobilizar e a se formar, e esse instrumento é o Partido Político da Classe Trabalhadora.Palavras-chave: Classe Trabalhadora. Sindicato. Partido Político.
(Fluorocyclopropyl)quinolones. 2. Synthesis and Stereochemical Structure-Activity Relationships of Chiral 7-(7-Amino-5-azaspiro[2.4]heptan-5-yl)-1-(2-fluorocyclopropyl)quinolone Antibacterial Agents (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT(Fluorocyclopropyl)quinolones. 2. Synthesis and Stereochemical Structure-Activity Relationships of Chiral 7-(7-Amino-5-azaspiro[2.4]heptan-5-yl)-1-(2-fluorocyclopropyl)quinolone Antibacterial AgentsYouichi Kimura, Shohgo Atarashi, Katsuhiro Kawakami, Kenichi Sato, and Isao HayakawaCite this: J. Med. Chem. 1994, 37, 20, 3344–3352Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://pubs.acs.org/doi/10.1021/jm00046a019https://doi.org/10.1021/jm00046a019research-articleACS PublicationsRequest reuse permissionsArticle Views2263Altmetric-Citations73LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
The granin family of uniquely acidic proteins of the diffuse neuroendocrine system: comparative and functional aspects (2004)

The chromogranins A (CgA) and B (CgB) and secretogranin II (SgII) constitute the main members of a family of uniquely acidic secretory proteins in elements of the diffuse neuroendocrine system. These genetically distinct proteins, CgA, CgB, SgII and the less well known secretogranins III-VII are collectively referred to as 'granins' and characterised by numerous pairs of basic amino acids as potential cleavage sites for processing by the co-stored prohormone converting enzymes PC 1/3 and PC2. This review is directed towards comparative and functional aspects of the granins with emphasis on their phylogenetically conserved sequences. Recent developments provide ample evidence of widely different effects and targets for the intact granins and their derived peptides, intracellularly in the directed trafficking of storage components during granule maturation and extracellularly in autocrine, paracrine and endocrine interactions. Most of the effects assigned to the granin derived peptides fit into patterns of direct or indirect inhibitory modulations of major functions. So far, peptides derived from CgA (vasostatins, chromacin, pancreastatin, WE-14, catestatin and parastatin), CgB (secretolytin) and SgII (secretoneurin) are the most likely candidates for granin-derived regulatory peptides, of postulated relevance not only for homeostatic processes, but also for tissue assembly and repair, inflammatory responses and the first line of defence against invading microorganisms.
Expression and Characterization of Recombinant Murine Factor VIII (2002)

Hemophilia A is the inherited bleeding disorder that results from mutation of blood coagulation factor VIII (fVIII). Described here is the generation of a regulated expression system producing recombinant murine fVIII. Murine B-domainless fVIII was expressed at a peak level of 4 units/106 cells/24 h in serum-free media. Subsequently, a two-step purification procedure resulted in 5,300-fold enrichment and a 70% yield. Highly purified recombinant murine fVIII had a specific coagulant activity of 660 units per nanomole. It underwent proteolytic processing by thrombin to yield an activated heterotrimer that demonstrated significantly greater stability than activated human fVIII. Recombinant murine fVIII was utilized to generate an anti-fVIII polyclonal antibody. Intravenous injection of recombinant murine fVIII into hemophilia A mice failed to induce a significant anti-fVIII immune response using a schedule that yielded high titer inhibitory antibodies to human fVIII. This may provide an important model for the study of immune tolerance to fVIII.
Learning Instance Occlusion for Panoptic Segmentation (2019)

Panoptic segmentation requires segments of both "things" (countable object instances) and "stuff" (uncountable and amorphous regions) within a single output. A common approach involves the fusion of instance segmentation (for "things") and semantic segmentation (for "stuff") into a non-overlapping placement of segments, and resolves overlaps. However, instance ordering with detection confidence do not correlate well with natural occlusion relationship. To resolve this issue, we propose a branch that is tasked with modeling how two instance masks should overlap one another as a binary relation. Our method, named OCFusion, is lightweight but particularly effective in the instance fusion process. OCFusion is trained with the ground truth relation derived automatically from the existing dataset annotations. We obtain state-of-the-art results on COCO and show competitive results on the Cityscapes panoptic segmentation benchmark.
Expression of the protective antigen of Bacillus anthracis by Lactobacillus casei: towards the development of an oral vaccine against anthrax (1999)

Bacillus anthracis is the causative organism of the disease anthrax. The ability of the organism to form resistant spores and infect via the aerosol route has led to it being considered as a potential biological warfare agent. The current available human vaccines are far from ideal, they are expensive to produce, require repeated doses and may invoke transient side-effects in some individuals. There is also evidence to suggest that they may not give full protection against all strains of B. anthracis. A new generation of anthrax vaccine is therefore needed. The use of Lactobacillus as a vector for expression of heterologous proteins from pathogens supplies us with a safe system, which can be given orally. Lactobacilli are commensals of the gut, generally regarded as safe and have intrinsic adjuvanticity. Oral vaccines may stimulate the mucosol immune system to produce local IgA responses in addition to systemic responses. These vectors are delivered at the mucosal surface, the site where the infection actually occurs and where the first line of defence lies. The gene encoding the protective antigen (PA) of B. anthracis, an immunogenic non-toxic component of the two toxins produced, is being cloned into different homologous vectors and subsequently transformed to various Lactobacillus strains. High intracellular expression levels for the PA in Lact. casei were achieved. Mucosal antigen presentation and humoral and cellular immune responses following immunization with transformants expressing PA in various ways (intracellular, surface-anchored and extracellular) are being studied.
Chitosan: a novel platform in proton-driven DNA strand rearrangement actuation (1900)

Nanometre-scaled DNA machine based on molecular recognition properties of DNA has now become a powerful tool in nanodevices, miniaturized structure, and nanofabrication. The common principle behind designing a DNA nanomachine is DNA strand exchange or rearrangement, which is solely controlled by the stabilization through associative and dissociative forces arising from base pair interaction of DNA molecules. Thus, highly effective DNA reaction actuator will make DNA nanomachine more flexible, controllable, and powerful device. Here, we report the novel polymer-mediated platform in proton-driven DNA strand rearrangement actuation. This cationic low molecular weight water-soluble chitosan (LMWSC) exhibited pH-dependent complexation with oligodeoxynucleotides (ODN). It formed complex with ODN only at low pH and accelerated the DNA strand exchange (or rearrangement) reaction between dsDNA and its complementary ssDNA at pH 5.0. However, no complexation was observed between LMWSC and ODN at neutral pH. We assume that at physiological pH, LMWSC is not protonated enough for formation of complex with ODN. Therefore, it can not diminish the electrostatic repulsion among the negatively charged DNA strands of the three-stranded intermediate formed during the strand exchange reaction. In contrast, LMWSC becomes positively charged at acidic pH, and it stabilizes the three-stranded intermediate by spreading out the accumulated counter-ions and increasing the entropy of the system. This fascinating observation prompted us to believe that this intelligent proton-driven DNA reaction actuator has a potential for the precise control of DNA nanomachine and would be applied for operating and controlling nanoscaled machine.
Collaborative control: a robot-centric model for vehicle teleoperation (2001)

Lausanne (EPFL) served as host institution (institution d’accueil) for this thesis and provided research facilities and infrastructure. Telerobotic systems have traditionally been designed and solely operated from a human point of view. Though this approach suffices for some domains, it is sub-optimal for tasks such as operating multiple vehicles or controlling planetary rovers. Thus, I believe it is worthwhile to examine a new system model for teleoperation: collaborative control. In collaborative control, a human and a robot collaborate to perform tasks and to achieve common goals. Instead of a supervisor dictating to a subordinate, the human and the robot engage in dialogue to exchange information, to ask questions, and to resolve differences. Instead of serving the human as a mere tool, the robot can operate more like a partner. With this approach, the robot has more freedom in execution and is more likely to find good solutions when there are problems. With collaborative control, the human is able to function as a resource for the robot, providing information and processing just like other system modules. In particular, the robot can ask the human questions as it works, to obtain assistance with cognition and perception during task
Advantages of next-generation sequencing versus the microarray in epigenetic research (2009)

Several recent studies from the field of epigenetics have combined chromatin-immunoprecipitation (ChIP) with next-generation high-throughput sequencing technologies to describe the locations of histone post-translational modifications (PTM) and DNA methylation genome-wide. While these reports begin to quench the chromatin biologists thirst for visualizing where in the genome epigenetic marks are placed, they also illustrate several advantages of sequencing based genomics compared to microarray analysis. Accordingly, next-generation sequencing (NGS) technologies are now challenging microarrays as the tool of choice for genome analysis. The increased affordability of comprehensive sequence-based genomic analysis will enable new questions to be addressed in many areas of biology. It is inevitable that massively-parallel sequencing platforms will supercede the microarray for many applications, however, there are niches for microarrays to fill and interestingly we may very well witness a symbiotic relationship between microarrays and high-throughput sequencing in the future.
Current Therapies and New Strategies for the Management of Alzheimer’s Disease (2010)

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that currently affects millions of Americans. There is no cure at present and no real long-term hope for patients with AD. While partially effective in improving symptoms, currently available treatments approved by the US Food and Drug Administration (FDA) do not halt progression of AD, or address the underlying mechanism of the disease, in part because the etiology of AD is still an active area of investigation. Identification of risk factors and the pathogenic mechanism of AD hold the promise of bringing forth novel treatments and perhaps even a cure. In this review, we will summarize some of the risk factors for AD, AD diagnosis, and current treatments. Novel therapeutic strategies such as inhibition of beta-amyloid peptide (Abeta), tau-mediated pathogenesis, and receptors for advanced glycation end products (RAGE), as well as neuroprotective and anti-inflammatory approaches and the impact of cholesterol-lowering, botanical, and nutritional agents are also reviewed.
Immunohistochemical distribution of type I, II and III collagens in the rabbit supraspinatus tendon insertion. (1994)

The collagen fibres in the area of attachment of the supraspinatus tendon to bone were studied immunohistochemically in 12 mature female New Zealand white rabbits. The labelling of type I collagen was uniformly prominent in the bone as well as in the fascicles of the tendon proper but inconspicuously scattered in the unmineralised and mineralised zones of the fibrocartilage. Type II collagen, not detected in the tendon proper, was widespread in both zones of the fibrocartilage. Type III collagen, on the other hand, appeared to be confined mainly to the zone of unmineralised fibrocartilage, in addition to its presence in the endotenon of the tendon proper. The region of the tidemark failed to show immunostaining for any of the collagen fibre types. In conclusion, this study demonstrates that, although all the principal fibrous collagen types are constituents of the supraspinatus tendon at its attachment site, the distribution pattern of immunolabelling varies from zone to zone.
Opposite Effects of β-cell Differentiation and Growth on Reg Expression in Human Fetal Pancreatic Cells (1994)

Reg is a gene associated with regeneration of pancreatic islets. We have previously shown that nicotinamide induces differentiation of human fetal beta-cells in tissue culture and that hepatocyte growth factor/scatter factor (HGF/SF) is mitogenic for the fetal beta-cells. We now tested whether these conditions, supporting either differentiation or growth, are associated with changes in reg gene expression in human fetal pancreatic cells. Culture for 7 days with 10 mM nicotinamide led to a fourfold decrease in reg mRNA levels (23 +/- 12% of control, n = 5, P < 0.001). In contrast, HGF/SF increased reg expression threefold (302 +/- 68% of control, n = 4, P < 0.05). Nicotinamide, which does not alter the differentiation level of adult beta-cells, did not significantly affect reg expression in adult human islets (84 +/- 4% of control, n = 2, NS). Thus, a higher level of endocrine differentiation is associated with a lower level of reg expression, and a higher rate of beta-cell replication results in increased reg transcription. These results provide the first evidence of a molecular marker, the reg gene, to distinguish between proliferation and differentiation of human beta-cells.