Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteasome inhibition slightly improves cardiac function in mice with hypertrophic cardiomyopathy

A growing line of evidence indicates a dysfunctional ubiquitin-proteasome system (UPS) in cardiac diseases. Anti-hypertrophic effects and improved cardiac function have been reported after treatment with proteasome inhibitors in experimental models of cardiac hypertrophy. Here we tested whether proteasome inhibition could also reverse the disease phenotype in a genetically-modified mouse model of hypertrophic cardiomyopathy (HCM), which carries a mutation in Mybpc3, encoding the myofilament protein cardiac myosin-binding protein C. At 7 weeks of age, homozygous mutant mice (KI) have 39% higher left ventricular mass-to-body-weight ratio and 29% lower fractional area shortening (FAS) than wild-type (WT) mice. Both groups were treated with epoxomicin (0.5 mg/kg/day) or vehicle for 1 week via osmotic minipumps. Epoxomicin inhibited the chymotrypsin-like activity by ~50% in both groups. All parameters of cardiac hypertrophy (including the fetal gene program) were not affected by epoxomicin treatment in both groups. In contrast, FAS was 12% and 35% higher in epoxomicin-treated than vehicle-treated WT and KI mice, respectively. To identify which genes or pathways could be involved in this positive effect, we performed a transcriptome analysis in KI and WT neonatal cardiac myocytes, treated or not with the proteasome inhibitor MG132 (1 μM, 24 h). This revealed 103 genes (four-fold difference; 5% FDR) which are commonly regulated in both KI and WT cardiac myocytes. Thus, even in genetically-modified mice with manifest HCM, proteasome inhibition showed beneficial effects, at least with regard to cardiac function. Targeting the UPS in cardiac diseases remains therefore a therapeutic option.
Services récréatifs en milieu naturel littoral et évaluation économique multi-attributs de la demande

Les services recreatifs fournis par le patrimoine naturel sont fortement heterogenes et, le plus souvent, non marchands. Pourtant la connaissance des preferences des visiteurs et de la valeur qu'ils attribuent a ces services est uine information cruciale pour le gestionnaire comme pour le decideur public. Cette these vise a contribuer au debat sur l'evaluation economique de la demande de loisir dans un environnement multidimensionnel. Elle examine les apports des methodes multi-attributs issues de l'approche de Lancaster et plus precisement de la Methode Multi-Programmes (MP) et de la Methode des Choix Multi-Attributs (MCMA). Ces approches, relativement recentes, visent a decomposer le service recreatif en differents attributs afin d'examiner les consequences de changement multidimensionnels dans leur fourniture et d'indentifier les arbitrages realises par les visiteurs entre les attributs. Nous proposons leur application aux "Plans Plages" girondins, sites littoraux offrant un acces a l'ocean, a la plage et a la foret. Une enquete a ete realisee aupres d'un echantillon de touristes et de residents (permanents et secondaires) durant l'ete 2006. La MP vise a tester l'existence d'un eventuel "effet de substitution" entre les programmes de maintien de la qualite recreative sur les espaces. Elle debouche egalement sur le calcul des Consentements-A-Payer des visiteurs. La MCMA appliquee au seul espace forestier, permet d'identifier les attributs du service recreatif ayant une influence dans le choix de visite. Au final, ces approches soulevent plusieurs questions quant a la formulation des choix individuels et leur prise en compte dans le processus d'evaluation.
The DNA hypomethylating agent, 5‐aza‐2′‐deoxycytidine, enhances tumor cell invasion through a transcription‐dependent modulation of MMP‐1 expression in human fibrosarcoma cells

In diseases such as cancer, cells need to degrade the extracellular matrix (ECM) and therefore require high protease levels. Thus, aberrant tissue degradation is associated to matrix metalloproteinases (MMPs) overexpression resulting from different mechanisms including epigenetic events. One of the most characterized epigenetic mechanisms is DNA methylation causing changes in chromatin conformation, thereby decreasing the accessibility to the transcriptional machinery and resulting in a robust gene silencing. Modulation of DNA methylation by DNA hypomethylating agents such as 5‐aza‐2′‐deoxycytidine (5‐azadC) is widely used in epigenetic anticancer treatments. Here, we focus on the effects of this drug on the expression level of MMP‐1, ‐2, and ‐9 in human HT1080 fibrosarcoma cells. We demonstrate that 5‐azadC increases MMP expression at both mRNA and protein levels, and promotes invasion potential of HT1080 cells. Using broad‐spectrum and specific MMP inhibitors, we establish that MMP‐1, but not MMP‐2 and ‐9, plays a key role in 5‐azadC‐enhanced cell invasion. We show that 5‐azadC induces MMP‐1 expression through a transcriptional mechanism without affecting MMP‐1 promoter methylation status. Finally, we demonstrate that 5‐azadC treatment increases the nuclear levels of Sp1 and Sp3 transcription factors, and modulates their recruitment to the MMP‐1 promoter, resulting in chromatin remodeling associated to 5‐azadC‐induced MMP‐1 expression. All together, our data indicate that the hypomethylating agent 5‐azadC modulates, mainly via Sp1 recruitment, MMP‐1 expression resulting in an increased invasive potential of HT1080 cells. © 2013 Wiley Periodicals, Inc.
A Platform for Scalable, Collaborative, Structured Information Integration

Freebase is as collaboratively created and edited database of general, structured information intended for broad public use. It is designed to scale to a large number and diversity of users and data. Both an AJAX/Web based user interface and an HTTP/JSON based API are provided to allow use by and collaboration between both humans and software. In particular, these interfaces allow for an “emergent workﬂow” of collaborative, distributed data structuring and entity reconciliation, even if individual users are not intentionally cooperating in such information integration tasks.
Physical dimensions of aging

The physical aging process progresses every day--and so does our understanding of it. "Physical Dimensions of Aging, Second Edition, " will keep students and professionals up to date on the outcomes of the latest research studies and their implications for the elderly in the real world. Physical aging affects us cognitively, psychologically, socially, and spiritually. The book discusses how people age physically and how this aging affects other dimensions of life.The second edition of "Physical Dimensions of Aging" has been updated to integrate research findings on physical aging from more than 100 different journals in myriad fields, creating interdisciplinary coverage on the topic. It provides students and professionals with what they need to know about physical aging in order to conduct clinical research and to work with clients and patients. In doing so, it retains its landmark status as the definitive reference on aging.Moreover, "Physical Dimensions of Aging, Second Edition, " focuses less on explaining the measurement techniques and research design and more on the outcome of the studies and their practical implications for everyday living. This approach will enable professionals and students to do the following: -Understand the physical aging process and its effects on other dimensions of life. -Apply the latest research in working with adults and the elderly. -Become more effective in their professions.The structure of this new edition is more conducive to learning and features the following: -Chapter objectives-Key terms-Sidebars of capsule research studies-Testimonials, vignettes, and other tidbits that tie the research information to the real world-Review questions to assist students in synthesizing and remembering the information-Short lists of recommended reading for those who want to pursue the topic in more detail-A glossary at the end of the bookThis second edition is organized into five parts. Part I provides an introduction to aging, to the field of gerontology, and to the research process for studying individual differences. Part II describes the physical changes in structure, capacity, and endurance. Part III overviews the factors related to motor coordination, motor control, and skill learning for older adults. Part IV addresses physical-psychosocial relationships, including health, exercise, and cognitive function as well as health-related expectations of quality of life for older adults. Part V highlights physical performance and achievement especially to showcase the results from consistent effort and hard work of physically elite older adults as inspiration for others.At a time when many people are telling older adults what they can't do, professionals should be telling them what they can do. "Physical Dimensions of Aging, Second Edition, " will equip professionals to do so.
Anti-PMSG antibody levels in sheep subjected annually to oestrus synchronisation.

Estimation of the long-term consequences on reproduction performance of the oestrus synchronisation treatments that are annually applied to ewes was carried out on nine officially controlled dairy flocks in the Roquefort region of France. A hormonal treatment combining the insertion of a vaginal fluoro-gestone acetate (FGA) sponge for 14 days and the injection of about 500 IU of pregnant mare serum gonadotropin (PMSG) at withdrawal was applied to the ewes in seven of the nine flocks. The ewes in the two other flocks were used as controls. Blood samples were taken from each female just before the treatment (to test for the presence of residual antibodies) and 20 days after the PMSG injection. Anti-PMSG antibody binding rates were calculated for each blood sample. The residual binding rate increased with age and induce negative effects on the following years reproduction performances, i.e., they increased the probability that the ewes would not become pregnant.
Chronic Cerebroventricular Infusion of Hypertonic Sodium Chloride in Rats Reduces Hypothalamic Sympatho‐Inhibition and Elevates Blood Pressure

To determine whether or not salt loading restricted to the brain would elevate blood pressure, chronically implanted osmotic minipumps were used to infuse hypertonic sodium chloride solutions made in artificial cerebrospinal fluid into a jugular vein intravenously or the third cerebral ventricle, intracerebroventricularly, for 11 days in awake rats. During intracere-broventricular infusion of hypertonic sodium chloride, tail-cuff systolic pressures began to rise on day 4 and were significantly elevated by day 9. In contrast, infusions of either artificial cerebrospinal fluid alone, intracerebroventricularly, or hypertonic sodium chloride, intravenously, were ineffective. Confirming the blood pressure elevation thereby detected, systolic and mean pressures recorded directly from indwelling aortic catheters after the same rats had been anesthetized with urethane on day 11, were also significantly higher following intracerebroventricular infusion of hypertonic sodium chloride than after infusion of artificial cerebrospinal fluid alone. Magnitude of depressor and sympatho-inhibitory responses elicited by graded electrical stimulation of the anterior hypothalamus invariably increased with the current strength used for stimulation. At all current strengths used for hypothalmic stimulation, depressor responses as well as attendant decreases in sympathetic neural firing, were smaller in rats that had been infused intracerebroventricularly with hypertonic sodium chloride than in any of the controls. Inhibition seemed specific for the anterior hypothalamus because pressor responses to stimulation of the ventro-medial hypothalamus were the same whether or not the intracerebroventricular infusion contained hypertonic sodium chloride. An explanation based on diminished cardiovascular sensitivity also appeared unlikely, since depressor responses to intravenously injected histamine were almost equal in both groups. Our results are compatible with the interpretation that hypertonic sodium chloride infused chronically into the 3rd ventricle acts by reducing anterior hypothalamic inhibition of sympathetic vasomotor tone, and that this, in turn, then elevates blood pressure.
Active Memory Processor: A Hardware Garbage Collector for Real-Time Java Embedded Devices

Java possesses many advantages for embedded system development, including fast product deployment, portability, security, and a small memory footprint. As Java makes inroads into the market for embedded systems, much effort is being invested in designing real-time garbage collectors. The proposed garbage-collected memory module, a bitmap-based processor with standard DRAM cells is introduced to improve the performance and predictability of dynamic memory management functions that include allocation, reference counting, and garbage collection. As a result, memory allocation can be done in constant time and sweeping can be performed in parallel by multiple modules. Thus, constant time sweeping is also achieved regardless of heap size. This is a major departure from the software counterparts where sweeping time depends largely on the size of the heap. In addition, the proposed design also supports limited-field reference counting, which has the advantage of distributing the processing cost throughout the execution. However, this cost can be quite large and results in higher power consumption due to frequent memory accesses and the complexity of the main processor. By doing reference counting operation in a coprocessor, the processing is done outside of the main processor. Moreover, the hardware cost of the proposed design is very modest (about 8000 gates). Our study has shown that 3-bit reference counting can eliminate the need to invoke the garbage collector in all tested applications. Moreover, it also reduces the amount of memory usage by 77 percent.
enitrifying bioreactors — An approach for reducing nitrate loads to eceiving waters

Low-cost and simple technologies are needed to reduce watershed export of excess nitrogen to sensitive aquatic ecosystems. Denitrifying bioreactors are an approach where solid carbon substrates are added into the flow path of contaminated water. These carbon (C) substrates (often fragmented wood-products) act as a C and energy source to support denitrification; the conversion of nitrate (NO3−) to nitrogen gases. Here, we summarize the different designs of denitrifying bioreactors that use a solid C substrate, their hydrological connections, effectiveness, and factors that limit their performance. The main denitrifying bioreactors are: denitrification walls (intercepting shallow groundwater), denitrifying beds (intercepting concentrated discharges) and denitrifying layers (intercepting soil leachate). Both denitrifcation walls and beds have proven successful in appropriate field settings with NO3− removal rates generally ranging from 0.01 to 3.6 g N m−3 day−1 for walls and 2–22 g N m−3 day−1 for beds, with the lower rates often associated with nitrate-limitations. Nitrate removal is also limited by the rate of C supply from degrading substrate and removal is operationally zero-order with respect to NO3− concentration primarily because the inputs of NO3− into studied bioreactors have been generally high. In bioreactors where NO3− is not fully depleted, removal rates generally increase with increasing temperature. Nitrate removal has been supported for up to 15 years without further maintenance or C supplementation because wood chips degrade sufficiently slowly under anoxic conditions. There have been few field-based comparisons of alternative C substrates to increase NO3− removal rates but laboratory trials suggest that some alternatives could sup− port greater rates of NO3 removal (e.g., corn cobs and wheat straw). Denitrifying bioreactors may have a number of adverse effects, such as production of nitrous oxide and leaching of dissolved organic matter (usually only for the first few months after construction and start-up). The relatively small amount of field data suggests that these problems can be adequately managed or minimized. An initial cost/benefit analysis demonstrates that denitrifying bioreactors are cost effective and complementary to other agricultural management practices aimed at decreasing nitrogen loads to surface waters. We conclude with her r t t 2 s recommendations for furt
Detoxification of electrophilic compounds by glutathione S‐transferase catalysis: Determinants of individual response to chemical carcinogens and chemotherapeutic drugs?

The glutathione S‐transferases (GSTs) catalyze the GSH‐dependent detoxification of reactive electrophiles such as genotoxic chemical carcinogens and cytotoxic chemotherapeutic agents. Allelic polymorphism in the GSTs has been used to investigate the hypothesis that GSTs are involved in susceptibility to human cancers. Such studies have resulted in low penetrance, high prevalence associations between cancer risk and GST polymorphisms. By examination of interindividual variation of GST expression it becomes clear that GST genotype alone is not an accurate predictor of GST expression. GST expression is tissue specific and interindividual variation of expression is at least 7‐fold in normal tissues. Thus, populations of the same genotype are actually heterogeneous as regards expression. Similarly, polymorphisms are not effective in all tissues and GST induction is not independent of genotype. Mechanistic models for chemical aspects of colorectal cancer and chemotherapy for breast cancer demonstrate some of the ways by which such interactions can be studied and the potential for future studies.
Actitud hacia la gastronomía local de los turistas: dimensiones y segmentación de mercado

This paper describes the attitude towards local gastronomy of the tourists coming to Valencia. For one out of four tourists gastronomy has more importance than other reasons (i.e. climate). The best valued traits of the local gastronomy image are the confidence in the ingredients, its healthy character, good taste and typical from Valencia. We can divide the different aspects we have studied in three groups: security, marketing and traditional/authentic. With them we have obtained three segments. The results show the high consumption of local products by tourists, and the high intention of continuing to consuming them in their country of origin if they were available.
Remote aircraft detection against terrain background and its implementation on SCAMP simulator

Though UAVs can autonomously fly by using GPS based waypoint navigation, they are practically blind during these flights, therefore they are considered to be a risk factor to other aircrafts. Due to limited payloads of small and medium sized UAVs, small, low power focal-plane array processor based vision system would be a good candidate for identifying intruder aircrafts. Identification of remote aircraft against sky background is already solved. This paper introduces an algorithm for identifying remote aircraft against terrain background. Some of the critical algorithmic components are implemented on the SCAMP simulator, which enables us to judge the accuracy and the speed of the algorithm.
Shared Story Reading

fully to promote literacy skills for all students. However, the benefits of shared story reading are not exclusive to literacy instruction and should carry into other disciplines, such as mathematics. Using shared story reading to teach mathematics concepts can play an important role in mathematics instruction for all students. What steps should teachers follow when using children’s literature as a contextual springboard to meaningful mathematics lessons for students with moderate and severe disabilities?
Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets.

BACKGROUND High rates of vancomycin failure in methicillin-resistant Staphylococcus aureus (MRSA) infections have been increasingly reported over time. The primary objective of our study was to determine the impact of vancomycin exposure and outcomes in patients with MRSA bacteremia initially treated with vancomycin. METHODS This was a single-center retrospective analysis of 320 patients with documented MRSA bacteremia initially treated with vancomycin from January 2005 through April 2010. Two methods of susceptibility, Etest and broth microdilution, were performed for all isolates to determine the correlation of susceptibility testing to patient outcomes. RESULTS Among a cohort of 320 patients, more than half (52.5%) experienced vancomycin failure. Independent predictors of vancomycin failure in logistic regression included infective endocarditis (adjusted odds ratio [AOR], 4.55; 95% confidence interval [CI], 2.26-9.15), nosocomial-acquired infection (AOR, 2.19; 95% CI, 1.21-3.97), initial vancomycin trough <15 mg/L (AOR, 2.00; 95% CI, 1.25-3.22), and vancomycin minimum inhibitory concentration (MIC) >1 mg/L by Etest (AOR, 1.52; 95% CI, 1.09-2.49). With use of Classification and Regression Tree (CART) analysis, patients with vancomycin area under the curve at 24 h (AUC(24h)) to MIC ratios <421 were found to have significantly higher rates of failure, compared with patients with AUC(24h) to MIC ratios >421 (61.2% vs 48.6%; P = .038). CONCLUSIONS In light of the high failure rates associated with this antimicrobial, optimizing the pharmacokinetic/pharmacodynamic properties of vancomycin by targeting higher trough values of 15-20 mg/L and AUC(24h)/MIC ratios ≥400 in selected patients should be considered.
A Novel Distributed Dynamic Location Management Scheme for Minimizing Signaling Costs in Mobile IP

Mobile IP is a simple and scalable global mobility solution. However, it may cause excessive signaling traffic and long signaling delay. Mobile IP regional registration is proposed to reduce the number of location updates to the home network and to reduce the signaling delay. This paper introduces a novel distributed and dynamic regional location management for Mobile IP where the signaling burden is evenly distributed and the regional network boundary is dynamically adjusted according to the up-to-date mobility and traffic load for each terminal. In our distributed system, each user has its own optimized system configuration which results in the minimal signaling traffic. In order to determine the signaling cost function, a new discrete analytical model is developed which captures the mobility and packet arrival pattern of a mobile terminal. This model does not impose any restrictions on the shape and the geographic location of subnets in the Internet. Given the average total location update and packet delivery cost, an iterative algorithm is then used to determine the optimal regional network size. Analytical results show that our distributed dynamic scheme outperforms the IETF Mobile IP regional registration scheme for various scenarios in terms of reducing the overall signaling cost.