Miracle-dz/UniFAR-FTUs huggingface dataset:
Calcineurin regulates slow myosin, but not fast myosin or metabolic enzymes, during fast‐to‐slow transformation in rabbit skeletal muscle cell culture

The addition of cyclosporin A (500 ng ml−1) ‐ an inhibitor of the Ca2+‐calmodulin‐regulated serine/threonine phosphatase calcineurin ‐ to primary cultures of rabbit skeletal muscle cells had no influence on the expression of fast myosin heavy chain (MHC) isoforms MHCIIa and MHCIId at the level of protein and mRNA, but reduced the expression of slow MHCI mRNA. In addition, no influence of cyclosporin A on the expression of citrate synthase (CS) and glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) mRNA was found. The level of enzyme activity of CS was also not affected. When the Ca2+ ionophore A23187 (4 × 10−7m) was added to the medium, a partial fast‐to‐slow transformation occurred. The level of MHCI mRNA increased, and the level of MHCIId mRNA decreased. Cotreatment with cyclosporin A was able to prevent the upregulation of MHCI at the level of mRNA as well as protein, but did not reverse the decrease in MHCIId expression. The expression of MHCIIa was also not influenced by cyclosporin A. Cyclosporin A was not able to prevent the upregulation of CS mRNA under Ca2+ ionophore treatment and failed to reduce the increased enzyme activity of CS. The expression of GAPDH mRNA was reduced under Ca2+ ionophore treatment and was not altered under cotreatment with cyclosporin A. When the myotubes in the primary muscle culture were electrostimulated at 1 Hz for 15 min periods followed by pauses of 30 min, a partial fast‐to‐slow transformation was induced. Again, cotreatment with cyclosporin A prevented the upregulation of MHCI at the level of mRNA and protein without affecting MHCIId expression. The nuclear translocation of the calcineurin‐regulated transcription factor nuclear factor of activated thymocytes (NFATc1) during treatment with Ca2+ ionophore, and the prevention of the translocation in the presence of cyclosporin A, were demonstrated immunocytochemically in the myotubes of the primary culture. The effects of cyclosporin A demonstrate the involvement of calcineurin‐dependent signalling pathways in controlling the expression of MHCI, but not of MHCIIa, MHCIId, CS and GAPDH, during Ca2+ ionophore‐ and electrostimulation‐induced fast‐to‐slow transformations. The data indicate a differential regulation of MHCI, of MHCII and of metabolism. Calcineurin alone is not sufficient to mediate the complete transformation.
Rickettsia rickettsii infection causes apoptotic death of cultured cerebellar granule neurons.

Rickettsia rickettsii is a small, Gram-negative, obligate intracellular bacillus and the causative agent of a fulminating human disease, Rocky Mountain spotted fever (RMSF) (Silverman, 1984). RMSF is a tick-borne disease wherein rickettsiae grow in the gut lining of ticks, often without harming the host. Human infection results either from a tick bite (commonest) or rarely by contamination of cut skin or a wound with faeces of the ticks (Bleck, 1999). In humans, R. rickettsii grows principally in endothelial cells of small blood vessels, producing vasculitis, thrombosis of vessels, fever, typical skin rash (petechial), organ dysfunctions and cell death (Walker & Raoult, 2000). Although the primary target of R. rickettsii is the vascular endothelial cell, often there is multi-organ and system involvement in the later stages of RMSF pathogenesis.
Low discriminating power of the modified Ottawa VTE risk score in a cohort of patients with cancer from the RIETE registry

Summary Treatment of patients with cancer-associated venous thromboembolism (VTE) remains a major challenge. The modified Ottawa score is a clinical prediction rule evaluating the risk of VTE recurrences during the first six months of anticoagulant treatment in patients with cancer-related VTE. We aimed to validate the Ottawa score using data from the RIETE registry. A total of 11,123 cancer patients with VTE were included in the analysis. According to modified Ottawa score, 2,343 (21%) were categorised at low risk for VTE recurrences, 4,525 (41%) at intermediate risk, and 4,255 (38%) at high risk. Overall, 477 episodes of VTE recurrences were recorded during the course of anticoagulant therapy, with an incidence rate for low, intermediate, and high risk groups of 6.88% (95% CI 5.31–8.77), 11.8% (95% CI 10.1–13.6), and 21.3% (95% CI 18.8–24.1) patient-years, respectively. Overall mortality had an incidence rate of 21.1% (95% CI 18.2–24.3), 79.4% (95% CI: 74.9–84.1), and 134.7% (95% CI: 128.3–141.4) patient-years, respectively. The accuracy and discriminating power of the modified Ottawa score for VTE recurrence was modest, with low sensitivity, specificity and positive predictive value, and a C-statistics of 0.58 (95% CI: 0.56–0.61). In our analysis, the modified Ottawa score did not accurately predict VTE recurrence among patients with cancer-associated thrombosis, thus hindering its use in clinical practice. It is time to define a new score including other clinical predictors.
Akt–RSK–S6 Kinase Signaling Networks Activated by Oncogenic Receptor Tyrosine Kinases

A phosphoproteomic analysis of signaling pathways downstream of oncogenic receptor tyrosine kinases identified potential therapeutic targets. Breaking a Deadly Addiction Most carcinomas are driven by aberrant signaling from receptor tyrosine kinases (RTKs) and, indeed, may become so dependent on these signals that they rely on them for survival. The enormous complexity of the downstream pathways, however, and the sheer numbers of potential targets, have made determining the substrates that mediate this “oncogene addiction” a daunting task. Moritz et al. developed a phosphoproteomic approach to identify targets of three core signaling pathways—all of which involve activation of AGC family kinases—downstream of oncogenic RTKs. They identified more than 300 phosphorylation targets of these signaling pathways, including a set of proteins downstream of three different oncogenic RTKs [c-Met, epidermal growth factor receptor (EGFR), and platelet-derived growth factor receptor α (PDGFRα)]. Moreover, they identified six targets of RTK signaling whose knockdown affected cell viability. A detailed analysis of one of these proteins—the chaperone SGTA—revealed a role for it in stabilization of PDGFRα and survival of cancer cells addicted to PDGFRα signaling. Receptor tyrosine kinases (RTKs) activate pathways mediated by serine-threonine kinases, such as the PI3K (phosphatidylinositol 3-kinase)–Akt pathway, the Ras–MAPK (mitogen-activated protein kinase)–RSK (ribosomal S6 kinase) pathway, and the mTOR (mammalian target of rapamycin)–p70 S6 pathway, that control important aspects of cell growth, proliferation, and survival. The Akt, RSK, and p70 S6 family of protein kinases transmits signals by phosphorylating substrates on an RxRxxS/T motif (R, arginine; S, serine; T, threonine; and x, any amino acid). We developed a large-scale proteomic approach to identify more than 300 substrates of this kinase family in cancer cell lines driven by the c-Met, epidermal growth factor receptor (EGFR), or platelet-derived growth factor receptor α (PDGFRα) RTKs. We identified a subset of proteins with RxRxxS/T sites for which phosphorylation was decreased by RTK inhibitors (RTKIs), as well as by inhibitors of the PI3K, mTOR, and MAPK pathways, and we determined the effects of small interfering RNA directed against these substrates on cell viability. Phosphorylation of the protein chaperone SGTA (small glutamine-rich tetratricopeptide repeat–containing protein α) at serine-305 was essential for PDGFRα stabilization and cell survival in PDGFRα-dependent cancer cells. Our approach provides a new view of RTK and Akt–RSK–S6 kinase signaling, revealing previously unidentified Akt–RSK–S6 kinase substrates that merit further consideration as targets for combination therapy with RTKIs.
ORM‐10103, a novel specific inhibitor of the Na+/Ca2+ exchanger, decreases early and delayed afterdepolarizations in the canine heart

At present there are no small molecule inhibitors that show strong selectivity for the Na+/Ca2+ exchanger (NCX). Hence, we studied the electrophysiological effects of acute administration of ORM‐10103, a new NCX inhibitor, on the NCX and L‐type Ca2+ currents and on the formation of early and delayed afterdepolarizations.
Evolutive Deep Models for Online Learning on Datastreams with no Storage

In recent years Deep Learning based methods gained a growing recognition in many applications and became the state-of-the-art approach in various fields of Machine Learning, such as Object Recognition, Scene Understanding, Natural Language processing and others. Nevertheless, most of the applications of Deep Learning use static datasets which do not change over time. This scenario does not respond well to a big number of recent applications (such as tendency analysis on social networks, video surveillance, sensor monitoring, etc.), especially when working with data streams which require real-time adaptation to the content of the data. In this paper, we propose a model that is able to perform online data classification and can adapt to data classes, never seen by the model before, while preserving previously learned information. Our approach does not need to store and reuse previous observations, which is a big advantage for data-streams applications, since the dataset one wants to work with can potentially be of very large size. To make up for the absence of previous data, the proposed model uses a recently developed Generative Adversarial Network to drive a Deep Convolutional Network for the main classification task. More specifically, we propagate generative models instead of the data itself, to be able to regenerate the historical training data that we didn't keep. We test our proposition on the well known MNIST benchmark database, where our method achieves results close to the state of the art convolutional networks trained by using the full dataset. We also study the impact of dataset re-generation with GANs on the learning process.
Relation between acute kidney injury and multiple‐organ failure: The chicken and the egg question*

2003, 12(Supp II):ii17–ii23 8. Pronovost P, Weast B, Holzmueller C, et al: Evaluation of the culture of safety: survey of clinicians and managers in an academic medical center. Qual Saf Health Care 2003; 12:405–410 9. Scott T, Mannion R, Davies H, et al: The quantitative measurement of organizational culture in health care: A review of the available instruments. Health Serv Res 2003; 38:923 10. Weingart S, Farbstein K, Davis R, et al: Using a multihospital survey to examine the safety culture. Jt Comm J Qual Saf 2004; 30: 125–132 11. Minvielle E, Dervaux B, Retbi A, et al: Culture, organization, and management in intensive care: Construction and validation of a multidimensional questionnaire. J Crit Care 2005; 20:126–138 12. Huang DT, Clermont G, Sexton JB, et al: Perceptions of safety culture vary between the intensive care units of a single institution. Crit Care Med 2007; 35:165–176 13. Helmreich R: Cockpit management attitudes. Hum Factors 1984; 26:583–589 14. Helmreich R, Schaefer H: Team performance in the operating room. In: Human Error in Medicine. Bogner M (Ed). Hillsdale, NJ, Lawrence Erlbaum Associates, 1994, pp 225–253 15. Scott T, Mannion R, Marshall M, et al: Does organisational culture influence health care performance? A review of the evidence. J Health Serv Res Policy 2003; 8:105–117 16. Tucker AL, Edmondson AC: Why hospitals don’t learn from failures: Organizational and psychological dynamics that inhibit system change. Calif Manage Rev 2003; 45:55 17. Gaba D, Singer S, Sinaiko A, et al: Differences in safety climate between hospital personnel and navy aviators. Hum Factors 2003; 45:173–185 18. Sexton JB, Thomas EJ, Helmreich RL: Error, stress, and teamwork in medicine and aviation: Cross sectional surveys. BMJ 2000; 320: 745–749 19. Singer SJ, Gaba DM, Geppert JJ, et al: The culture of safety in California hospitals. Qual Saf Health Care 2003; 12:112–118 20. Thomas E, Sexton J, Helmreich R: Discrepant attitudes about teamwork among critical care nurses and physicians. Crit Care Med 2003; 31:956–959 21. Sexton J, Holzmueller C, Pronovost P, et al: Variation in caregiver perceptions of teamwork climate in labor and delivery units. J Perinatol 2006; 32:407–410, 357 22. Agency for Healthcare Research and Quality (AHRQ), AHRQ Quality Indicators: Guide to Patient Safety Indicators. Rockville, MD, Agency for Healthcare Research and Quality, 2006
Attitudes and Sexual Prejudice in Sport and Physical Activity

This study focused on attitudes and sexual prejudice as part of a larger project on inclusive practice in sport and physical activity settings. Questionnaires were administered to a large sample of undergraduate students and to selected samples of upper-level preprofessional students and a campus pride group to investigate attitudes toward gays and lesbians, and other minority groups. Attitude scores were in the middle range, with females more positive than males toward gay men. Evaluation Thermometer scores were generally positive, but markedly lower for gay men and lesbians than for other minority groups. Upper-level preprofessional students were more positive than other undergraduates, but still expressed negative attitudes toward lesbians and gay men. These results confirm persistent sexual prejudice, suggest that attention to sexual minorities is particularly important for effective diversity management, and underscore the need for continuing research and educational programs to enhance cultural comp.
ENHANCING THE SOLUBILITY OF RAMIPRIL USING A NEW ESSENTIAL OIL BASED MICROEMULSION SYSTEM

Ramipril is a good angiotensin converting enzyme (ACE) inhibitor. This drug is found to be poorly aqueous insoluble due to its lipophilic nature. But the efficacy of the drug directly depends on the solubility. Hence, we tried to improve on the solubility using a new lipophilic environment. Our novel microemulsion drug delivery system for ramipril was formulated using cinnamon oil, tween 20 and water (6:30:64 v/v) without any highenergy methods. The optimized formulation was checked for various parameters to demonstrate the internal state of the system. Cinnamon oil based drug-incorporated system (F5) showed higher solubility, hydrodynamic diameter of 9-48 nm and good stability. Also, the surfactant concentration was found to have a direct relation to stability and viscosity. Moreover, the system due to the presence of cinnamon oil may have additional influence on the efficacy against certain pathogens. Thus, our novel formulation has added advantage in serving as best drug delivery agent for ramipril.
Binding of a biosynthetic intermediate to AtrA modulates the production of lidamycin by Streptomyces globisporus

The control of secondary production in streptomycetes involves the funneling of environmental and physiological signals to the cluster‐situated (transcriptional) regulators (CSRs) of the biosynthetic genes. For some systems, the binding of biosynthetic products to the CSR has been shown to provide negative feedback. Here we show for the production of lidamycin (C‐1027), a clinically relevant antitumor agent, by Streptomyces globisporus that negative feedback can extend to a point higher in the regulatory cascade. We show that the DNA‐binding activity of the S. globisporus orthologue of AtrA, which was initially described as a transcriptional activator of actinorhodin biosynthesis in S. coelicolor, is inhibited by the binding of heptaene, a biosynthetic intermediate of lidamycin. Additional experiments described here show that S. globisporus AtrA binds in vivo as well as in vitro to the promoter region of the gene encoding SgcR1, one of the CSRs of lidamycin production. The feedback to the pleiotropic regulator AtrA is likely to provide a mechanism for coordinating the production of lidamycin with that of other secondary metabolites. The activity of AtrA is also regulated by actinorhodin. As AtrA is evolutionarily conserved, negative feedback of the type described here may be widespread within the streptomycetes.
Horizontally Differentiated Store Brands: Production Outsourcing to National Brand Manufacturers

We study a retailer's strategic decision with regard to outsourcing the production of such types of store brands (SBs) to national brand (NB) manufacturers. The wholesale price of NB is assumed to be set by the manufacturer, while that of the SB is assumed to be set by the retailer. When a retailer outsources SB production to an NB manufacturer, the NB manufacturer might suffer from cannibalization due to offering both the SB and the NB, implying that a strategic interaction between the retailer and manufacturer is an important issue. Based on this motivation, we mainly focus on the strategy of a dominant retailer in such a situation and investigate it with a game-theoretic approach. We show that the optimal strategy for the SB retailer sensitively depends on the degree of differentiation between the SB and the NB. In particular, if both products are less differentiated, the retailer benefits from offering only the SB, and, in this case, the retailer should offer its wholesale price, after the manufacturer sets the NB wholesale price. Furthermore, it is shown that the optimal strategies of the retailer are socially efficient, if and only if the SB and the NB are sufficiently differentiated.
The heat-modifiable outer membrane protein of Actinobacillus actinomycetemcomitans: relationship to OmpA proteins

The outer membrane of Actinobacillus actinomycetemcomitans contains a 29-kDa protein which exhibits heat modifiability on sodium dodecyl sulfate-polyacrylamide gels and represents a major target for immunoglobulin G antibody in sera of periodontitis patients colonized by this organism. In the present study, the N-terminal amino acid sequence of the 29-kDa outer membrane protein was determined and compared with reported sequences for other known proteins. The heat-modifiable outer membrane protein of A. actinomycetemcomitans was found to exhibit significant N-terminal homology with the OmpA proteins of other gram-negative bacteria. Moreover, this protein reacted with antiserum raised against the purified OmpA protein of Escherichia coli K-12. Whether the heat-modifiable OMP of A. actinomycetemcomitans also shares functional properties of OmpA proteins, particularly with respect to bacteriophage receptor activity, is presently under investigation.
Non-local active contours

This thesis deals with image segmentation problems that arise in various computer vision related fields such as medical imaging, satellite imaging, video surveillance, recognition and robotic vision. More specifically, this thesis deals with a special class of image segmentation technique called Snakes or Active Contour Models. In active contour models, image segmentation is posed as an energy minimization problem, where an objective energy function (based on certain image related features) is defined on the segmenting curve (contour). Typically, a gradient descent energy minimization approach is used to drive the initial contour towards a minimum for the defined energy. The drawback associated with this approach is that the contour has a tendency to get stuck at undesired local minima caused by subtle and undesired image features/edges. Thus, active contour based curve evolution approaches are very sensitive to initialization and noise. The central theme of this thesis is to develop techniques that can make active contour models robust against certain classes of local minima by incorporating global information in energy minimization. These techniques lead to energy minimization with global considerations; we call these models – 'Non-local active contours'. In this thesis, we consider three widely used active contour models: 1) Edge- and region-based segmentation model, 2) Prior shape knowledge based segmentation model, and 3) Motion segmentation model. We analyze the traditional techniques used for these models and establish the need for robust models that avoid local minima. We address the local minima problem for each model by adding global image considerations.
Correction: Transcriptome Analysis of Barbarea vulgaris Infested with Diamondback Moth (Plutella xylostella) Larvae

Background: The diamondback moth (DBM, Plutella xylostella) is a crucifer-specific pest that causes significant crop losses worldwide. Barbarea vulgaris (Brassicaceae) can resist DBM and other herbivorous insects by producing feeding-deterrent triterpenoid saponins. Plant breeders have long aimed to transfer this insect resistance to other crops. However, a lack of knowledge on the biosynthetic pathways and regulatory networks of these insecticidal saponins has hindered their practical application. A pyrosequencing-based transcriptome analysis of B. vulgaris during DBM larval feeding was performed to identify genes and gene networks responsible for saponin biosynthesis and its regulation at the genome level.
Using Dialogue Acts to Suggest Responses in Support Services via Instant Messaging

Instant messaging dialogue is real-time, text-based computer-mediated communication conducted over the Internet. Messages sent over instant messaging can be encoded We propose a method of using dialogue acts to predict utterances in taskoriented dialogue. Dialogue acts provide a semantic representation of utterances in a dialogue. An evaluation using a dialogue simulation program shows that our proposed method of predicting responses provides useful suggestions for almost all response types.