Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles

We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La3+- and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45-CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca2+ concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca2+ concentrations similar to those present in the SR lumen after depolarization-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs

psort

psort \ue8 stato il pi\uf9 veloce software di ordinamento per macchine di classe PC dal 2008 al 2011 (benchmark Pennysort, http://sortbenchmark.org) e un suo adattamento per cluster ha migliorato il record per il benchmark datamation di quasi un ordine di grandezza nel 2011. Il rapporto tecnico ufficiale si trova sul sito sortbenchmark.org (che cataloga i pi\uf9 efficienti software di ordinamento per varie categorie di task/hardware - originariamente mantenuto dal premio Turing Jim Gray) all'URL http://sortbenchmark.org/psort_2011.pdf -- Ulteriori dettagli si possono trovare nelle pubblicazioni: P. Bertasi, M. Bressan, E. Peserico. psort, yet another fast stable sorting software, ACM Journal of Experimental Algorithmics, vol. 16, 2011 -- P. Bertasi, M. Bonazza, M. Bressan, E. Peserico. Datamation: a quarter of a century and four orders of magnitude later. Proc. of IEEE CLUSTER 201

Towards a Combination of Online and Multitask Learning for MT Quality Estimation: a Preliminary Study.

Quality estimation (QE) for machine translation has emerged as a promising way to provide real-world applications with methods to estimate at run-time the reliability of automatic translations. Real-world applications, however, pose challenges that go beyond those of current QE evaluation settings. For instance, the heterogeneity and the scarce availability of training data might contribute to significantly raise the bar. To address these issues we compare two alternative machine learning paradigms, namely online and multi-task learning, measuring their capability to overcome the limitations of current batch methods. The results of our experiments, which are carried out in the same experimental setting, demonstrate the effectiveness of the two methods and suggest their complementarity. This indicates, as a promising research avenue, the possibility to combine their strengths into an online multi-task approach to the problem

generating e commerce product titles and predicting their quality

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TMop: a Tool for Unsupervised Translation Memory Cleaning

We present TMop, the first open-source tool for automatic Translation Memory (TM) cleaning. The tool implements a fully unsupervised approach to the task, which allows spotting unreliable translation units (sentence pairs in different languages, which are supposed to be translations of each other) without requiring labeled training data. TMop includes a highly configurable and extensible set of filters capturing different aspects of translation quality. It has been evaluated on a test set composed of 1,000 translation units (TUs) randomly extracted from the English-Italian version of MyMemory, a large-scale public TM. Results indicate its effectiveness in automatic removing “bad” TUs, with comparable performance to a state-of-the-art supervised method (76.3 vs. 77.7 balanced accuracy)

transcrater a tool for automatic speech recognition quality estimation

We present TranscRater, an open-source tool for automatic speech recognition (ASR) quality estimation (QE). The tool allows users to perform ASR evaluation bypassing the need of reference transcripts and confidence information, which is common to current assessment protocols. TranscRater includes: i) methods to extract a variety of quality indicators from (signal, transcription) pairs and ii) machine learning algorithms which make possible to build ASR QE models exploiting the extracted features. Confirming the positive results of previous evaluations, new experiments with TranscRater indicate its effectiveness both in WER prediction and transcription ranking tasks

Immunotherapy for colorectal cancer: where are we heading?

Introduction: In the last few years, significant advances in molecular biology have provided new therapeutic options for colorectal cancer (CRC). The development of new drugs that target the immune response to cancer cells seems very promising and has already been established for other tumor types. In particular, the use of immune checkpoint inhibitors seems to be an encouraging immunotherapeutic strategy. Areas covered: In this review, the authors provide an update of the current evidence related to this topic, though most immunotherapies are still in early-phase clinical trials for CRC. To understand the key role of immunotherapy in CRC, the authors discuss the delicate balance between immune-stimulating and immune-suppressive networks that occur in the tumor microenvironment. Expert opinion: Modulation of the immune system through checkpoint inhibition is an emerging approach in CRC therapy. Nevertheless, selection criteria that could enable the identification of patients who may benefit from these agents are necessary. Furthermore, potential prognostic and predictive immune biomarkers based on immune and molecular classifications have been proposed. As expected, additional studies are required to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and enhance effector response

Elevated Serum Uric Acid Concentrations Independently Predict Cardiovascular Mortality in Type 2 Diabetic Patients

OBJECTIVE\u2014 There is limited information on whether increased serum uric acid levels are independently associated with cardiovascular mortality in type 2 diabetes. We assessed thepredictive role of serum uric acid levels on all-cause and cardiovascular mortality in a large cohort of type 2 diabetic individuals.RESEARCH DESIGN AND METHODS\u2014 The cohort included 2,726 type 2 diabetic outpatients, who were followed for a mean period of 4.7 years. The independent association of serum uric acid levels with all-cause and cardiovascular mortality was assessed by Cox proportional hazards models and adjusted for conventional risk factors and several potential confounders.RESULTS\u2014 During follow-up, 329 (12.1%) patients died, 44.1% (n = 145) of whom from cardiovascular causes. In univariate analysis, higher serum uric acid levels were significantly associated with increased risk of all-cause (hazard ratio 19 [95% CI 1.12\u20131.27], P < 0.001) and cardiovascular (1.25 [1.16 \u20131.34], P < 0.001) mortality. After adjustment for age, sex, BMI, smoking, hypertension, dyslipidemia, diabetes duration, A1C, medication use (allopurinol or hypoglycemic, antihypertensive, lipid-lowering, and antiplatelet drugs), estimated glomerular filtration rate, and albuminuria, the association of serum uric acid with cardiovascular mortalityremained statistically significant (1.27 [1.01\u20131.61], P = 0.046), whereas the association of serum uric acid with all-cause mortality did not.CONCLUSIONS\u2014 Higher serum uric acid levels are associated with increased risk of cardiovascular mortality in type 2 diabetic patients, independent of several potential confounders, including renal function measures

Temperature-induced melting of double-stranded DNA in the absence and presence of covalently bonded antitumour drugs: insight from molecular dynamics simulations

The difference in melting temperature of a double-stranded (ds) DNA molecule in the absence and presence of bound ligands can provide experimental information about the stabilization brought about by ligand binding. By simulating the dynamic behaviour of a duplex of sequence 5′-d(TAATAACGGATTATT)·5′-d(AATAATCCGTTATTA) in 0.1 M NaCl aqueous solution at 400 K, we have characterized in atomic detail its complete thermal denaturation profile in <200 ns. A striking asymmetry was observed on both sides of the central CGG triplet and the strand separation process was shown to be strongly affected by bonding in the minor groove of the prototypical interstrand crosslinker mitomycin C or the monofunctional tetrahydroisoquinolines trabectedin (Yondelis®), Zalypsis® and PM01183®. Progressive helix unzipping was clearly interspersed with some reannealing events, which were most noticeable in the oligonucleotides containing the monoadducts, which maintained an average of 6 bp in the central region at the end of the simulations. These significant differences attest to the demonstrated ability of these drugs to stabilize dsDNA, stall replication and transcription forks, and recruit DNA repair proteins. This stabilization, quantified here in terms of undisrupted base pairs, supports the view that these monoadducts can functionally mimic a DNA interstrand crosslink

Infraestrutura verde para monitorar e minimizar os impactos da poluição atmosférica

RESUMO O Material Particulado (MP) está entre os principais contaminantes do ar. A Infraestrutura Verde (IV) vem sendo reconhecida como alternativa para melhorar a qualidade do ar. As árvores podem afetar diretamente os níveis de MP, interceptando partículas em sua superfície. Devido a essa capacidade, esta pesquisa teve como objetivo contribuir com informações sobre a viabilidade da vegetação verde para interceptar e identificar as principais fontes de poluentes atmosféricos. Amostras de cascas de árvores de parques urbanos de São Paulo (SP) foram utilizadas como monitor biológico de poluentes atmosféricos. Foi observado um decaimento exponencial das concentrações e aprisionamento de poluentes em direção à região mais interna dos parques. Além disso, foi possível distinguir a emissão de veículos leves das emissões de veículos pesados. O baixo custo do monitoramento e sua eficácia mostram que a IV ocupa papel de destaque na melhoria da saúde e a qualidade de vida das pessoas, bem como nas ações que buscam atenuar os efeitos da poluição do ar em cidades de médio e grande porte