Miracle-dz/UniFAR-FTUs huggingface dataset:
A monoclonal antibody directed against human von Willebrand factor induces type 2B‐like alterations

Summary. We have previously described a monoclonal antibody (mAb), 1C1E7, against von Willebrand factor (VWF), that increases ristocetin‐induced platelet aggregation (RIPA) and induces a preferential binding of the high‐molecular‐weight multimers of VWF to platelet GPIb. Further investigations using a rotational viscometer at a shear rate of 4000 s−1 could now demonstrate that shear‐induced platelet aggregation (SIPA) is significantly increased with 1C1E7 and that this could be completely inhibited by the anti‐GPIb mAb 6D1. In contrast, platelet adhesion to a collagen surface at a shear rate of 2600 s−1, using a rectangular perfusion chamber, was significantly inhibited in the presence of 1C1E7. When citrated whole blood was incubated with 1C1E7, a spontaneous binding of VWF to the platelet GPIb could be demonstrated by flow cytometric analysis. Parallel to this, a decrease of the highest molecular weight multimers of VWF in the plasma was found. Platelets with bound VWF on their surface were able to form macroaggregates but were no longer able to adhere. These phenomena are very similar to the alterations described in von Willebrand's disease type 2B. The epitope of this mAb could be localized to the N‐terminal part of the subunit; therefore a distant conformational change in the A1 domain of VWF is suggested.
LyF-1, a transcriptional regulator that interacts with a novel class of promoters for lymphocyte-specific genes

We have studied transcriptional control of the murine terminal deoxynucleotidyltransferase (TdT) gene, which is activated specifically in immature B and T lymphocytes. This analysis has led to the identification and purification of a 50-kDa sequence-specific DNA-binding protein, LyF-1, that interacts with the approximate consensus sequence PyPyTGGGAGPu and is enriched in cells at most stages of B- and T-cell differentiation. LyF-1 binds tightly to an element in the TdT promoter that we show is required for transcription in lymphocytes. LyF-1 also interacts with an element in the immunoglobulin mu enhancer, called microB, that was recently shown to be important for lymphocyte-specific enhancer activity. Moreover, LyF-1 binds to the promoters for the lymphocyte-specific genes lambda 5, VpreB, and lck, all of which we speculate have additional features in common with the TdT promoter. Thus, LyF-1 may be a general transcriptional activator for genes whose expression is restricted to the B- and/or T-lymphocyte lineages.
Quantitative Dynamics of Plasmodium yoelii Sporozoite Transmission by Infected Anopheline Mosquitoes

ABSTRACT Malaria transmission begins with the injection of Plasmodium sporozoites into the skin of a vertebrate host by infected anopheline mosquitoes. Although the size of the sporozoite inoculum likely affects the course of the disease, the number of sporozoites injected by infected mosquitoes has not been determined in vivo. Using a quantitative PCR assay, we determined the number of sporozoites injected into mice by single mosquitoes. Analysis of 59 mosquito feedings showed that a single infected mosquito injected between 0 and 1,297 sporozoites, with a mean of 123 and a median of 18. Twenty-two percent of infected mosquitoes injected no sporozoites. The number of sporozoites injected was only weakly correlated to the salivary gland load. To better understand the large variability in sporozoite injection among mosquitoes, we quantified the sporozoites injected by individual mosquitoes on three different days. Approximately 20% of moderately to heavily infected mosquitoes injected few to no sporozoites on all 3 days, suggesting that some mosquitoes are poor transmitters of sporozoites. Other mosquitoes injected high numbers of sporozoites on at least one of the days observed and minimal numbers on the other day(s), supporting the hypothesis that sporozoite injection is discontinuous, a pattern that may aid in the establishment of malaria infection.
Pentoxifylline Inhibits Integrin-Mediated Adherence of 12(S)-HETE and TNFα-Activated B16F10 Cells to Fibronectin and Endothelial Cells

Background: Pentoxifylline (PTX), a phosphodiesterase inhibitor, inhibits homing of metastatic B16F10 melanoma cells to the lung. Studies on the mechanism of action of PTX showed inhibition of adhesion of cultured melanoma cells to various extracellular matrix substrates and inhibition of cell surface integrin expression. The aim of this study was to determine the effect of PTX on surface expression of integrin and integrin-mediated adhesion induced by biological mediators, tumour necrosis factor (TNF) α and 12(S)-hydroxyeicosatetraenoic acid (HETE), in B16F10 cells. Materials and Methods: B16F10 cells were treated with 12(S)-HETE (1 µM, 1 h), TNFα (5 ng/ml, 2 h) and phorbol 12-myristate 13-acetate (400 nM, 20 min), and the effect of PTX on these treatments was studied by flow cytometry, adhesion assay and confocal microscopy. Results: 12(S)-HETE and TNFα brought about an increase in the surface expression of β1 integrins and F10 cell adhesion to fibronectin and endothelial cells; this increased adhesion was mediated at least in part by alterations in the localization of β1 integrins. Pretreatment with PTX was able to completely abrogate this induction in integrin expression. Conclusion: PTX can inhibit surface expression of integrin and integrin-mediated adhesion induced by several biological mediators, and this might be a possible mechanism for its antimetastatic action, in vivo.
The optimum marker for the detection of lymphatic vessels

Podoplanin, lymphatic vessel endothelial hyaluronic acid receptor-1, prospero-related homeobox-1 and vascular endothelial growth factor receptor 3 have been demonstrated to have crucial roles in the development of the lymphatic system and lymphangiogenesis process by combining with their corresponding receptors. Thus, the four markers have been widely used in labelling lymphatic vessels for the detection of lymphangiogenesis and lymphatic vessel invasion. Numerous authors have aimed to identify the roles of these four markers in the lymphatic system and the mechanisms have been partly clarified at the molecular level. The aim of the present review was to comprehensively clarify the characteristics and latent action modes of the four markers in order to determine which is the best one for the detection of lymphangiogenesis and lymphatic vessel invasion.
Who's Cheating Whom?.

An article about cheating practically writes itself. It must begin, of course, with a shocking statistic or two to demonstrate the pervasiveness of the problem, perhaps accompanied by a telling anecdote or a quotation from a shrugging student (“Well, sure, everyone does it”). This would be followed by a review of different variants of unethical behavior and a look at who is most likely to cheat. Finally, a list of ideas must be provided for how we can deter or catch cheaters, along with a stern call for greater vigilance.
Responsible Development of Self-learning Assisted Living Technology for Older Adults with Mild Cognitive Impairment or Dementia

In this paper we present work in progress in the Assisted Living Project – responsible innovations for dignified lives at home for people with mild cognitive impairment or dementia. The project has a distinctly interdisciplinary approach and engages experts in nursing and occupational therapy, in ethics and responsible research and innovation, and in technology, in particular automation and machine learning. Our approach is to involve the end-users, their family and their care providers and develop technology responsibly together with them. The technological approach employs self-learning systems to develop solutions that provide individualised support in accordance with the user’s values, choices, and preferences. The paper presents our approach, current findings and future plans.
Community Knowledge Sharing in Practice: The Eureka Story

An organization’s most valuable knowledge—its essential intellectual capital—is not limited to the information in ofcial document repositories and databases, such as scientic formulae, ‘‘hard’’ research data, computer codes, codied procedures, nancial gures, customer records, and the like. It also includes the largely undocumented ideas, insights, and know-how of its members (see, for example, Nonaka and Takeuchi, 1995; Stewart, 1997; Davenport and Prusak, 1997; Senge et al., 1999). This informal (often tacit) knowledge is deeply rooted in individuals’ experiences and the culture of their work communities. It commonly originates as practical solutions— through everyday inventions and discoveries—to the problems they must solve and thus serves as the critical resource for ordinary work practice (see, especially, Brown and Duguid, 1991, 2000). Much of this knowledge often remains embedded in practice. Small circles of colleagues and work groups commonly share crucial steps in a new practice and fresh solutions to recalcitrant problems through conversations and stories, with members  lling in the background and gaps from their own experience. These groups and communities use the local vernacular to express these instructions and stories. Organizations face the challenge of somehow converting this valuable but mainly local knowledge into forms that other members of the organization can understand and, perhaps most important, act on. Here we present a detailed account of one organization’s effort to encourage inventiveness, capture new ideas, and use technology to then share the best of this knowledge beyond a local work group. Our account is based on our experiences during seven years with the design, development, deployment, and evaluation of the Eureka system at Xerox Corporation. Xerox uses Eureka to support the customer service engineers (CSEs) who repair the copiers and printers installed at customer sites. In four iterations, the system went from an experiment that researchers at the Xerox Palo Alto Research Center (PARC) designed to measure the value of codied eld experience to a system deployed to 20,000 CSEs worldwide. By focusing on communities and how they share knowledge in ordinary practice, we developed a set of questions and a methodology that we hope will enable others to build similar community knowledge-sharing systems. However, deploying any knowledge system involves pushing changes within a corporate culture; understanding the Eureka experience and the problems facing all knowledge systems to be deployed in the real world requires equal focus on these challenges. Our narrative covers the history of this project, carefully detailing the fundamental interrelationships between the social and the technical.We include a framework for building these kinds of community systems (see the sidebar) and our reections on the barriers to organizational change that their proponents confront.
Histological and Ultrastructural Studies on the Intestine of Guntea Loach, Lepidocephalichthys Guntea (Cypriniformes, Cobitidae)

Abstract The cellular organizations of intestine in Lepidocephalichthys guntea (Hamilton, 1822) have been described by light as well as scanning and transmission electron microscopy. The intestine is short and straight like, marked into anterior, middle and posterior region based on mucosal folds, number and size of columnar epithelial cells and mucous cells, thickness of submucosa and muscularis layer. The mucosa of anterior intestine forms high folds, which are lined with compactly arranged columnar epithelial cells and mucous cells. In the middle intestine, folds are pointless whereas the posterior intestine is without folds. The submucosa is formed of thin layer of connective tissue, contained collagen bundles and blood capillaries, comparatively well developed in the posterior intestine. By scanning electron microscopy, outlines of the luminal surface of anterior and middle intestine is embossed with oval or rounded columnar epithelial cells contained densely packed stubby microridges. The posterior intestine has closely set longitudinal folds characterized with minute blood capillaries and columnar epithelial cells having inconspicuous microridges. Ultrastructurally, the mucosal surface of the intestine consists of mucous cells with electron dense granules and columnar epithelial cells having numerous microvilli, mitochondria, endoplasmic reticulum, lysosomes and Golgi body. Cellular components of the anterior and middle intestine participate in the absorption whereas the presence of enormous blood vessels and capillary net work of posterior intestine probably responsible for air breathing.
Optimizing risk stratification in cardiac rehabilitation with inclusion of a comorbidity index.

PURPOSE The risk stratification criteria of the American Association of Cardiovascular and Pulmonary Rehabilitation include guidelines to be used in stratifying cardiac rehabilitation (CR) patients for risk of disease progression (long term) and clinical events (short term). Noncardiac comorbidities are not included as indicators in these criteria. This study was designed to ascertain the prevalence of noncardiac comorbidities among CR patients, and to assess their relation to the current risk stratification algorithm for clinical events. METHODS Patients were stratified into high-, intermediate-, and low-risk groups according to the American Association of Cardiovascular and Pulmonary Rehabilitation risk stratification criteria for clinical events (ARSE) at program entry. Within each risk group, age, gender, race, and noncardiac comorbidities were ascertained. Comorbidities were summarized in a comorbidity index (CMI). The relation between clinical events and risk status by ARSE and CMI was evaluated by logistic regression. RESULTS Among 490 patients (age, 60 +/- 12 years; 35% women; 30% nonwhite) enrolled in CR with ischemic heart disease, the number of comorbidities ranged from 0 to 7 (median, 2; 75th percentile, 3). The patients categorized in the three ARSE groups differed significantly in age and comorbidities. Although ARSE tended to identify patients with a greater comorbidity burden, 38% of the patients with a comorbidity index exceeding the 75th percentile were not classified in the highest ARSE group. Clinical events increased across ARSE and CMI risk strata. Both ARSE and CMI were independent predictors of events in an age-, gender-, and race-adjusted logistic regression analysis (ARSE odds ratio [OR], 1.56; 95% confidence interval [CI], 1.14-2.12; CMI OR, 1.23, 95% CI, 1.03a-1.47). Events were predicted best when both classifications were combined. Exploratory gender-specific analyses suggested that ARSE performed better among men than among women, whereas CMI was a more important predictor among women. CONCLUSIONS To appreciate more fully the overall complexity of disease among CR patients, ARSE should be supplemented not only with the inclusion of cardiac risk factors, as suggested in the current guidelines, but also with an assessment of noncardiac comorbidities.
Calnexin acts as a molecular chaperone during the folding of glycoprotein B of human cytomegalovirus

Human cytomegalovirus glycoprotein B (gB) is synthesized as a 105-kDa nonglycosylated polypeptide and cotranslationally modified by addition of N-linked oligosaccharides to a 160-kDa precursor in the endoplasmic reticulum (ER). It is then transported to the Golgi complex, where it is endoproteolytically cleaved to form the disulfide-linked mature gp55-116 complex. Pulse-chase experiments demonstrate that the 160-kDa gB precursor was transiently associated with calnexin, a membrane-bound chaperone, in the ER. The association was maximal immediately after synthesis, and they dissociated with a half-time of 15 min. Complete inhibition of binding by tunicamycin or castanospermine indicates the importance of N-linked oligosaccharides for it. Nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that during an initial stage in the biogenesis, the 160-kDa gB precursor was first synthesized as a fully reduced form and rapidly converted to an oxidized form, with a half-time of 18 min. Both forms of the gB precursor could bind to calnexin. The kinetics of the conversion from the fully reduced to the oxidized form coincided with that of dissociation of the 160-kDa gB precursor from calnexin, suggesting that the two steps are closely related.
Well-Being and Control in Older Persons: The Prediction of Well-Being from Control Measures

The interrelation of six facets of control and their ability to predict well-being in older persons were studied in an age and gender stratified community sample aged fifty-five to eighty-nine. An extended conceptual framework of control facets is introduced including “established” facets, such as mastery, self-efficacy and internal health locus of control and “new” control facets such as neuroticism, social inadequacy, and sense of coherence. An interview and a postal questionnaire included measures of the control facets and the Affect Balance Scale. Correlations between control measures were mostly modest. Negative affect was predicted by neuroticism and sense of coherence. Tendencies of independent association of mastery with global well-being and of social inadequacy with positive affect were established.
The in vitro evaluation of isolated procyanidins as modulators of cytokine-induced eotaxin production in human alveolar epithelial cells

BACKGROUND: Populations that consume procyanidin-rich diets are less susceptible to inflammatory disease. Allergic asthma is an inflammatory lung disease perpetuated by a hyperreactive airway epithelium and eosinophil infiltration into the lung. Eotaxin-1 (CCL11) mediates eosinophil migration into tissues and its modulation could represent a means to assist the management of airway inflammation. OBJECTIVE: Here we evaluated procyanidins as a means of modulating CCL11 production in vitro. METHODS: We used human lung epithelial cells (A549) and optimized the conditions to induce CCL11 production in vitro. Cells were exposed to procyanidins for 6 h prior to an inflammatory insult of 5 ng/mL IL-4 with 5 ng/mL TNF for 48 h. An enzyme-linked immunosorbent assay was used to measure CCL11 production. RESULTS: Cells exposed to 5 M procyanidin A2 prior to the inflammatory challenge showed significantly inhibited (36%) CCL11 production. Under the same conditions, procyanidins B1 and B2 elicited no effect. Furthermore, combinations of procyanidins A2 and B2 (5 M total) demonstrated no evidence of a synergistic interaction. CONCLUSIONS: These data demonstrate that the regulation of CCL11 by lung epithelial cells is not ubiquitous among the three investigated procyanidins. We demonstrate a differential inhibition of CCL11 by A-type and B-type procyanidins. This evidence supports further studies into procyanidins, specifically A-type, for managing inappropriate airway inflammation.
Multicontact vector fields on Hessenberg manifolds

In 1850, Liouville proved that any C conformal map between domains in R is necessarily the restriction of the action of one element of O(1, 4). Cowling, De Mari, Koranyi and Reimann recently prove a Liouvilletype result: they defined a generalized contact structure on homogeneous spaces of the type G/P, where G is a semisimple Lie group and P a minimal parabolic subgroup, and they show that the group of “contact” mappings coincides with G. In this paper, we consider the problem of characterizing the “contact” mappings on a natural class of submanifolds of G/P, namely the Hessenberg manifolds. Mathematics subject classification 2000: 22E46, 53A30, 57S20.
Molecular Tyrosine Phosphatases Regulate AMPA Receptor Trafficking during Metabotropic Glutamate Receptor-Mediated Long-Term Depression

Two forms of long-term depression (LTD), triggered by activation of NMDA receptors (NMDARs) and metabotropic glutamate receptors (mGluRs), respectively, can be induced at CA1 synapses in the hippocampus. Compared with NMDAR-LTD, relatively little is known about mGluR-LTD. Here, we show that protein tyrosine phosphatase (PTP) inhibitors, orthovanadate and phenylarsine oxide, selectively block mGluR-LTD induced by application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG-LTD), because NMDAR-LTD is unaffected by these inhibitors. Furthermore, DHPG-LTD measured using whole-cell recording is similarly blocked by either bath-applied or patch-loaded PTP inhibitors. These inhibitors also block the changes in paired-pulse facilitation and coefficient of variation that are associated with the expression of DHPG-LTD. DHPG treatment of hippocampal slices was associated with a decrease in the level of tyrosine phosphorylation of GluR2 AMPA receptor (AMPAR) subunits, an effect blocked by orthovanadate. Finally, in dissociated hippocampal neurons, orthovanadate blocked the ability of DHPG to reduce the number of AMPA receptor clusters on the surface of dendrites. Again, the effects of PTP blockade were selective, because NMDA-induced decreases in surface AMPAR clusters was unaffected by orthovanadate. Together, these data suggest that activation of postsynaptic PTP results in tyrosine dephosphorylation of AMPARs and their removal from the synapse.
A Phase Calibration Method Based on Phase Gradient Autofocus for Airborne Holographic SAR Imaging

Holographic synthetic aperture radar tomography can realize full 3-D reconstructions of objects over 360° with very high resolution, and thus becomes an interesting 3-D imaging technique. However, due to the uncompensated platform motion errors, phase errors among different tracks usually exist in this imaging mode, which will hinder the 3-D image focusing. In this letter, a phase calibration method based on phase gradient autofocus is proposed to mitigate the influence of these phase errors. It exploits the space-invariant characteristic of the phase errors in a limited scene and uses an efficient and robust multibaseline autofocus to calibrate the phase errors among the multiple circular tracks. Experimental results with the GOTCHA real data are carried out to demonstrate the validity and feasibility of the proposed method.
GAD-reactive CD 4 1 Th 1 Cells Induce Diabetes in NOD / SCID Mice

Although glutamic acid decarboxylase (GAD) has been implicated in IDDM, there is no direct evidence showing GAD-reactive T cells are diabetogenic in vivo. To address this issue, 3-wk-old NOD mice received two injections of purified rat brain GAD; one mouse rapidly developed diabetes 3 wk later. Splenocytes from this mouse showed a proliferative response to purified GAD, and were used to generate a CD4 1 T cell line, designated 5A, that expresses TCRs encoding V b 2 and V b 12. 5A T cells exhibit a MHC restricted proliferative response to purified GAD, as well as GAD65 peptide 524–543. After antigen-specific stimulation, 5A T cells secrete IFN g and TNF a / b , but not IL-4. They are also cytotoxic against NOD-derived hybridoma cells (expressing I-A g7 ) that were transfected with rat GAD65, but not nontransfected hybridoma cells. Adoptive transfer of 5A cells into NOD/SCID mice produced insulitis in all mice. Diabetes occurred in 83% of the mice. We conclude that GAD injection in young NOD mice may, in some cases, provoke diabetes due to the activation of diabetogenic T cells reactive to GAD65 peptides. Our data provide direct evidence that GAD65 autoimmunity may be a critical event in the pathogenesis of IDDM. ( J. Clin. Invest. 1998. 101:68– 73.)