Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating microparticles and procoagulant activity in elderly patients.

BACKGROUND Microparticles (MP) are shed membrane vesicles released from activation or apoptosis of several cell types and carry a procoagulant activity. Age is associated with a procoagulant state, but the role of MP in this setting is unknown, as the relationship of MP to aging in humans. We tested the hypotheses that elderly persons compared with young persons may have different patterns of expression of MP and procoagulant activity in stable or septic conditions. METHODS Patients from Emergency and Geriatric Departments were divided into four groups according to their age (< 50 or > or = 75 years old) and the presence of systemic infection (yes or no). The diagnosis of infection was reached when it was classified as certain or possible by an expert panel. Circulating MP were isolated from venous citrated blood. Cytofluorometry using specific antibodies was performed to determine the origins of MP (endothelial microparticles [EMP], red blood cell microparticles, or platelet microparticles). Procoagulant activity was determined using annexin V (prothrombinase activity) and tissue factor (TF) assays. RESULTS One hundred and eleven patients were included. Elderly patients expressed a decrease in EMP in stable conditions, associated with a decrease in procoagulant annexin V MP in septic conditions (p < .05), and higher EMP levels were found in elderly infected patients who died during hospital stay than in survivors (p = .04). Compared with young patients, response to sepsis was altered in elders concerning EMP, annexin V MP, and TF-bearing MP. CONCLUSION Elderly patients expressed a different pattern of MP in stable conditions, with a different response to sepsis in procoagulant activity modification.
Chloroquine Inhibits Autophagy to Potentiate Antiestrogen Responsiveness in ER+ Breast Cancer

Purpose: Estrogen receptor-α (ERα)-targeted therapies including tamoxifen (TAM) or Faslodex (ICI) are used to treat ER+ breast cancers. Up to 50% of tumors will acquire resistance to these interventions. Autophagy has been implicated as a major driver of antiestrogen resistance. We have explored the ability of chloroquine (CQ), which inhibits autophagy, to affect antiestrogen responsiveness. Experimental Design: TAM-resistant MCF7-RR and ICI-resistant/TAM cross-resistant LCC9 ER+ breast cancer cells were injected into mammary fat pads of female athymic mice and treated with TAM and/or ICI in combination with oral low-dose CQ. Results: We show that CQ can increase antiestrogen responsiveness in MCF7-RR and LCC9 cells and tumors, likely through the inhibition of autophagy. However, the combination of ICI+CQ was less effective than CQ alone in vivo, unlike the TAM+CQ combination. Antiestrogen treatment stimulated angiogenesis in tumors but did not prevent CQ effectiveness. The lower efficacy of ICI+CQ was associated with ICI effects on cell-mediated immunity within the tumor microenvironment. The mouse chemokine KC (CXCL1) and IFNγ were differentially regulated by both TAM and ICI treatments, suggesting a possible effect on macrophage development/activity. Consistent with these observations, TAM+CQ treatment increased tumor CD68+ cells infiltration, whereas ICI and ICI+CQ reduced peripheral tumor macrophage content. Moreover, macrophage elimination of breast cancer target cells in vitro was reduced following exposure to ICI. Conclusion: CQ restores antiestrogen sensitivity to resistant tumors. Moreover, the beneficial combination of TAM+CQ suggests a positive outcome for ongoing neoadjuvant clinical trials using this combination for the treatment of ER+ ductal carcinoma in situ lesions. Clin Cancer Res; 20(12); 3222–32. ©2014 AACR.
Designing antibodies for the inhibition of gastrin activity in tumoral cell lines

Gastrin and its derivatives are becoming important targets for immunotherapy of pancreatic, gastric and colorectal tumors. This study was conducted to design antibodies able to block gastrin binding to the gastrin/cholecystokinin‐2 (CCK‐2) receptor in order to delay tumor growth. The authors have used different gastrin molecules, combined with the diphtheria toxoid, to generate and select human single chain variable fragments (scFvs) as well as mouse monoclonal antibodies and scFvs against different regions of gastrin. There was a remarkable conservation in the antibody repertoire against gastrin, independently of the approach and the species. The germlines most frequently used in gastrin antibody formation were identified. Three different epitopes were identified in the gastrin molecule. The resulting mouse monoclonal antibodies and scFvs were analyzed for gastrin neutralization using Colo 320 WT cells, which overexpress the CCK‐2 receptor. The gastrin neutralizing activity assay showed that N‐terminal specific mouse monoclonal antibodies were more efficient to inhibit proliferation of Colo 320 WT cells than the anti‐C terminal antibodies. Moreover, the human antigastrin scFvs obtained in this study inhibited significantly the proliferation of Colo 320 tumoral cells. These findings should contribute to a more rational design of antibody‐based antigastrin therapies in cancer, including passive administration of human antibodies with blocking activity. © 2008 Wiley‐Liss, Inc.
Serine Hydrolase Inhibitors Block Necrotic Cell Death by Preventing Calcium Overload of the Mitochondria and Permeability Transition Pore Formation*

Background: Mitochondrial calcium overload triggers permeability transition pore formation, fatty acid release, and necrotic cell death. Results: Pyrrophenone and KT195 inhibit cell death by blocking mitochondrial calcium uptake. Conclusion: Serine hydrolase inhibitors block mitochondrial calcium uptake but do not directly inhibit the enzyme releasing fatty acids during pore formation. Significance: Serine hydrolase inhibitors have potential to block necrotic cell death associated with disease. Perturbation of calcium signaling that occurs during cell injury and disease, promotes cell death. In mouse lung fibroblasts A23187 triggered mitochondrial permeability transition pore (MPTP) formation, lactate dehydrogenase (LDH) release, and necrotic cell death that were blocked by cyclosporin A (CsA) and EGTA. LDH release temporally correlated with arachidonic acid release but did not involve cytosolic phospholipase A2α (cPLA2α) or calcium-independent PLA2. Surprisingly, release of arachidonic acid and LDH from cPLA2α-deficient fibroblasts was inhibited by the cPLA2α inhibitor pyrrophenone, and another serine hydrolase inhibitor KT195, by preventing mitochondrial calcium uptake. Inhibitors of calcium/calmodulin-dependent protein kinase II, a mitochondrial Ca2+ uniporter (MCU) regulator, also prevented MPTP formation and arachidonic acid release induced by A23187 and H2O2. Pyrrophenone blocked MCU-mediated mitochondrial calcium uptake in permeabilized fibroblasts but not in isolated mitochondria. Unlike pyrrophenone, the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol and CsA blocked cell death and arachidonic acid release not by preventing mitochondrial calcium uptake but by inhibiting MPTP formation. In fibroblasts stimulated with thapsigargin, which induces MPTP formation by a direct effect on mitochondria, LDH and arachidonic acid release were blocked by CsA and 1-oleoyl-2-acetyl-sn-glycerol but not by pyrrophenone or EGTA. Therefore serine hydrolase inhibitors prevent necrotic cell death by blocking mitochondrial calcium uptake but not the enzyme releasing fatty acids that occurs by a novel pathway during MPTP formation. This work reveals the potential for development of small molecule cell-permeable serine hydrolase inhibitors that block MCU-mediated mitochondrial calcium overload, MPTP formation, and necrotic cell death.
To wrap or not wrap? What is expected? Some initial findings from a study on gift wrapping

This paper aims to explore and discuss the expectations surrounding the decision to wrap a gift. Gift wrapping can enable an object to be turned into a gift through the development of meaning that symbolises it as a gift. There are two key expectations surrounding the use of gift wrapping. The first expectation is that receivers prefer gifts to be wrapped and the second expectation is that the gift meets individual and social expectations of what a gift should look like. Data was gathered using three qualitative techniques; observation, interviews and projective workshops. These initial findings form part of a larger research study into gift wrapping.
How do novice teachers in Finland perceive their professional agency?

This study investigated novice teachers’ perceptions of their professional agency during the initial years of their work in schools. The research questions were: (i) How do novice teachers perceive their professional agency within their work, and what do they see as the main restrictions and resources affecting that agency? (ii) How do novice teachers perceive their professional agency in the construction and renegotiation of their professional identities, and what do they see as the main restrictions and resources affecting their sense of agency? In theoretical terms, we adhere to a subject-centered sociocultural approach. This implies understanding subjects as active agents from a developmental perspective, with attention also given to professional identities. The subjects of this study were 13 qualified primary-level class teachers who had worked from one to five years as class teachers in Finnish primary schools. Data from open-ended interviews with the novice teachers were analyzed using thematic analysis. The findings indicated that all the novice teachers perceived strong agency in their opportunities to apply and develop pedagogical practices within the classroom. However, they had a much weaker sense of agency as regards the social management of the classroom. When the teachers entered into the practical school context, most of them became aware that they would have to renegotiate their professional identities. This involved re-assessing their professional ideals and ethical standards. The major perceived constraint emerged from their lack of competence in providing support for the children’s psychological well-being. The role of the school principal was seen crucial for the novice teachers’ work in the schools: the principal was seen as acting as a resource but also as a constraint on the teacher’s sense of professional agency, both at the individual and school levels. In addition, close collaboration and support from other teachers in difficult everyday situations was seen as crucial for the teachers’ survival in the practical school context. The study provides insights into the challenges and constraints affecting novice teachers’ sense of professional agency, and on the resources and support that they need in their first years at work.
Sexuality in context: Variation and the sociolinguistic perception of identity

This article illustrates the use of an empirical method for examining the perceptual identification of gayness in male speakers. It demonstrates how, by digitally manipulating the speech of isolated individuals, it is possible to obtain reliable evidence that pitch range and sibilant duration may act as indexical of a gay male identity. Further scrutiny of this result, however, illustrates that linguistic indexicality is not as straightforward as it originally appears. Subsequent analyses of the data highlight the ways in which the perceptual evaluation of sexuality is a highly contingent process, dependent upon a variety of sociolinguistic factors. An envelope of variation in listeners' affective judgments of a speaker is shown to exist, and it is argued that research on the perception of identity must go beyond identification of salient features, and also consider when and why these features are not salient.I greatly benefited from the insight and assistance of the following people, whom I would like to thank: Renée Blake, Lisa Davidson, Penny Eckert, Rudi Gaudio, Ron Butters, Keith Walters, Barbara Johnstone, and three anonymous reviewers. Earlier versions of this article were presented at the Linguistic Society of America Annual Meeting in Oakland, California, in January 2005, and the 72nd Southeastern Conference on Linguistics (SECOL) in Raleigh, North Carolina in April 2005. I thank the participants at those events for their questions and comments. All errors are, of course, my own.
Integrating Students with Moderate and Severe Disabilities into General Education Classes

Interviews were conducted to gather advice about integration from general and special education teachers and administrators from 10 schools in five school districts where students with moderate and severe disabilities had recently been integrated into general education schools and classrooms. The study explored not only the educational change process, but general educators' perceptions of factors that had initially created and later reduced their resistance to integration. Qualitative analysis of interview data revealed teachers' perceptions of the success of integration, as well as their advice to others contemplating integration: district administrators, building administrators, special education teachers, and general education teachers.
Emotional Connection, Materialism, and Religiosity: An Islamic Tourism Experience

ABSTRACT Materialism and Islamic religiosity have been studied in tourism, but the influence of these concepts on the emotional connections established during an actual religious experience has yet to be explored. This study develops a model that links Islamic religiosity and materialism with the religious experience, communitas, and emotional connection with a sample of 538 Iranian Umrah participants using partial least squares. The study found significant effects of religious connection upon emotional connection. The research also identified the positive influence of Islamic religiosity upon communitas and the religious experience, alongside a negative impact of materialism on the religious experience.
Impact of Recasts and Prompts on the Learning of English Third Person Singular Marker by Persian Learners of English

Based on the controversial beliefs among L2 teachers about effective corrective feedback (CF) strategies, recast and prompts as 2 kinds of CF have drawn the attention of L2 researchers(e.g., Braidi, 2002; Iwashita, 2003; Loewen & Philp, 2006; Panova & Lyster, 2002; Sheen, 2004). Despite these numbers of studies, debate continues to exist about their usefulness as a CF technique. Whereas recasts provide a correct reformulation of L2 learners‘ nontarget utterance, the other alternative type of feedback in L2 classroom settings is referred to as prompts (Lyster, 2004) because they provide signals that prompt L2 learners to selfrepair rather than provide them with a correct reformulation of their nontarget utterance. Hence, the focus of this study was to examine the effect of recasts in comparison to prompts on the learning of English third person singular marker ―s‖ by Iranian preintermediate L2 learners. Two CF techniques of recasts and prompts were utilized in 2 experimental groups in response to their errors in using the correct form of the verb for third person singular subject. In the third group as the control group, No-CF was provided by the L2 teacher. The results revealed that the Prompts Group had outperformed the Recast Group and No-CF Group. Thus, it could be concluded that prompts as a CF strategy led to more gains than CF that provided the L2 learners with the correct form (recast) than No-CF.
Court Culture: An Explanation of Variations in the Use of Bail by Magistrates’ Courts

It has long been recognised that there are significant variations in the use of bail in magistrates’ courts. A recent study carried out in South Wales suggests that these variations cannot be fully accounted for by differences in the cases heard. The findings suggest that the explanation lies in the culture of the courts and the effect that this has on the working practices of participants, principally the Crown Prosecution Service (CPS) and defence solicitors which in turn reinforces and perpetuates the ‘court culture’.
Functional Organization for Direction of Motion and Its Relationship to Orientation Maps in Cat Area 18

The goal of this study was to explore the functional organization of direction of motion in cat area 18. Optical imaging was used to record the activity of populations of neurons. We found a patchy distribution of cortical regions exhibiting preference for one direction over the opposite direction of motion. The degree of clustering according to preference of direction was two to four times smaller than that observed for orientation. In general, direction preference changed smoothly along the cortical surface; however, discontinuities in the direction maps were observed. These discontinuities formed lines that separated pairs of patches with preference for opposite directions. The functional maps for direction and for orientation preference were closely related; typically, an iso-orientation patch was divided into regions that exhibited preference for opposite directions, orthogonal to the orientation. In addition, the lines of discontinuity within the direction map often connected points of singularity in the orientation map. Although the organization of both domains was related, the direction and the orientation selective responses were separable; whereas the selective response according to direction of motion was nearly independent of the length of bars used for visual stimulation, the selective response to orientation decreased significantly with decreasing length of the bars. Extensive single and multiunit electrical recordings, targeted to selected domains of the functional maps, confirmed the features revealed by optical imaging. We conclude that significant processing of direction of motion is performed early in the cat visual pathway.
TGFβ induces SIK to negatively regulate type I receptor kinase signaling

Signal transduction by transforming growth factor β (TGFβ) coordinates physiological responses in diverse cell types. TGFβ signals via type I and type II receptor serine/threonine kinases and intracellular Smad proteins that regulate transcription. Strength and duration of TGFβ signaling is largely dependent on a negative-feedback program initiated during signal progression. We have identified an inducible gene target of TGFβ/Smad signaling, the salt-inducible kinase (SIK), which negatively regulates signaling together with Smad7. SIK and Smad7 form a complex and cooperate to down-regulate the activated type I receptor ALK5. We further show that both the kinase and ubiquitin-associated domain of SIK are required for proper ALK5 degradation, with ubiquitin functioning to enhance SIK-mediated receptor degradation. Loss of endogenous SIK results in enhanced gene responses of the fibrotic and cytostatic programs of TGFβ. We thus identify in SIK a negative regulator that controls TGFβ receptor turnover and physiological signaling.
Vertical Antenna Tilt Optimization for LTE Base Stations

An optimal vertical antenna tilt in a wireless access network plays a key role for coverage and capacity in the system. The autonomous (re-)optimization of tilts bears a large saving potential for operators as manual intervention is particularly costly. In this paper, we present a heuristic variant of the gradient ascent method to continuously optimize antenna tilts with quick convergence. We show that the average spectral efficiency in the system increases by 10% and that the spectral efficiency at the cell edge (5% quantile) increases by 100% after optimization. Changing conditions during the operational phase of the network, as for instance cell outage, can successfully be detected and compensated by an autonomous re-optimization.
Perceived Racial Discrimination, Social Support, and Psychological Adjustment Among African American College Students

The purpose of this study was to examine three competing models of the relations among perceived discrimination, social support, and indicators of psychological adjustment in a sample of 135 African American college students. The three competing models, social support buffering, social support mobilization, and social support deterioration, were tested within a regression framework. The buffering model, which predicted that social support would interact with perceived discrimination such that individuals with high levels of social support would be protected from the harmful effects of discrimination, was not supported. The social support mobilization model, which predicted that support networks would mobilize to support individuals exposed to discrimination, was also not supported. Support was only obtained for the social support deterioration model, which predicted that social support would decrease for those exposed to discrimination. Perceived racial discrimination was associated with lower perceptions of social support, greater symptoms of depression, and lower levels of life satisfaction.
Long-term smoking results in haemostatic dysfunction in chronic smokers

Background: Smoking has been known to cause endothelial dysfunction and bronchial carcinoma and duration of smoking has been implicated in the effects of smoking on regular smokers. This study evaluated the effects of long-term smoking on some coagulation markers in chronic smokers. Materials and Methods: A total of 78 chronic smokers (age, 41 ± 20 years) where grouped according to duration of time they have smoked (2-6 years, 7-11 years, 12-16 years and 17-21 years), and included in the study. Bleeding time (BT), whole-blood clotting time (WBCT), total platelet count (TPC), prothrombin time (PT) and activated partial thromboplastin time with kaolin (APTTK) were estimated in the subjects using standard operative procedures. Statistical Analysis used: Graph pad prism software (Statmate) version 2.0 and SPSS version 20.0 were used for the statistical analysis and the test of significance was calculated using paired Student's t-test. Results: There was an inverse correlation between the durations of smoking and BT, WBCT, PT and APTTK coagulation markers and a linear correlation between the different durations and TPC, in the chronic smokers. The strongest effects was in the 12-16 years and 17-21 years duration (P < 0.05). Conclusion: The study revealed that long-term chronic cigarette-smoking can lead to haemostatic dysfunction in chronic smokers. Smoking should be generally discouraged as it could have far-reaching medical implications on this group of subjects, especially in bleeding emergency cases.
Computer-Aided Dynamic Characterization of Fourth-Order PWM DC–DC Converters

Average-value modeling of dc-dc converters has been an area of active research for many years. Developing accurate average-value models of higher order converters is further complicated by the presence of parasitics and waveform nonlinearity. This paper extends the numerical state-space averaging to the fourth-order capacitor-based switching stages. The proposed model takes into account conduction losses associated with switching-stage components and is seamlessly functional in all operational modes. The proposed model is validated with a hardware prototype and detailed simulation and is shown to accurately predict large-signal time-domain transients as well as small-signal frequency-domain characteristics.
Cultural Relativism vs. Universalism: Female Genital Mutilation, Pragmatic Remedies

This essay will discuss both universalistic and cultural relativist approaches as applied to female genital mutilation. Universal and cultural relativist feminists have vastly different views on this matter, my intention is to parallel each view and offer insight on the reason why Western feminists have coined this practice as “mutilation” as opposed to “cutting”. The intent of this paper is to explore efficient grounds for abolition while proposing antidotes using both cultural relativist and universalist perspectives.