A Study of the Day - Night Effect for the Super - Kamiokande Detector: I. Time Averaged Solar Neutrino Survival Probability

This is the first of two articles aimed at providing comprehensive predictions for the day-night (D-N) effect for the Super-Kamiokande detector in the case of the MSW \nu_e \to \numt transition solution of the solar neutrino problem. The one-year averaged probability of survival of the solar \nue crossing the Earth mantle, the core, the inner 2/3 of the core, and the (core + mantle) is calculated with high precision (better than 1%) using the elliptical orbit approximation (EOA) to describe the Earth motion around the Sun. Results for the survival probability in the indicated cases are obtained for a large set of values of the MSW transition parameters $\Delta m^2$ and $sin^22\theta_{V}$ from the ``conservative'' regions of the MSW solution, derived by taking into account possible relatively large uncertainties in the values of the $^{8}$B and $^{7}$Be neutrino fluxes. Our results show that the one-year averaged D-N asymmetry in the $\nu_e$ survival probability for neutrinos crossing the Earth core can be, in the case of $sin^22 \theta_{V} \leq 0.13$, larger than the asymmetry in the probability for (only mantle crossing + core crossing) neutrinos by a factor of up to six. The enhancement is larger in the case of neutrinos crossing the inner 2/3 of the core. This indicates that the Super-Kamiokande experiment might be able to test the $sin^22\theta_{V} \leq 0.01$ region of the MSW solution of the solar neutrino problem by performing selective D-N asymmetry measurements.Comment: LaTeX2e - 18 Text Pages + 21 figures = 39 Pages. - Figures in PS + text file sk1b14.tex requires two auxiliary files (included

Structural basis of phosphatidylinositol 3-kinase C2α function

Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine

Structural basis of phosphatidylinositol 3-kinase C2α function

Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine

cAMP-Dependent Co-stabilization of Axonal Arbors from Adjacent Developing Neurons

Axonal arbors in many neuronal networks are exuberant early during development and become refined by activity-dependent competitive mechanisms. Theoretical work proposed non-competitive interactions between co-active axons to co-stabilize their connections, but the demonstration of such interactions is lacking. Here, we provide experimental evidence that reducing cyclic AMP (cAMP) signaling in a subset of retinal ganglion cells favors the elimination of thalamic projections from neighboring neurons, pointing to a cAMP-dependent interaction that promotes axon stabilization

Prostate cancer, treatment modalities and complications: an evaluation of the scientific literature

Prostate (PR) cancer (CA) is one of the most common malignant neoplasms in men all over the world. In general, if prostate cancer (PC) is detected early, treatment usually involves either surgical removal of the prostate or radiotherapy (RT). Hormone Therapy (HT) or chemotherapy (CH) is the preferred treatment for more advanced cases of PC or if CA spreads beyond the PT. A number of complications, such as urinary incontinence (IU) or erectile dysfunction (ED), can be associated with some modalities of treatment of the PC. The aim of this work is to evaluate, in PubMed, the number of publications related with prostate cancer and the main modalities of treatment, as well as some clinical complications. The searches were performed in PubMed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) in the period 1950 to 2008 using the words: (i) CA, (ii) CA and PR or penis or testis, (iii) CA and PR and RT, CA and PR and surgery (SU), CA and PR and CH and, CA and PR and HT and (iv) CA and PR and RT and IU or ED, CA and PR and SU and IU or ED, CA and PR and CH and IU or ED and, CA and PR and HT and CH and IU or ED, and (V) PC and the same modalities of treatment. The data was obtained on July 20th, 2008. PC, as expected has been cited extensively and surgery has been identified as the most widely referenced modality of treatment. Furthermore, urinary incontinence and erectile dysfunction are important complications that have attracted significant scientific interest. In conclusion, these findings have shown the relevance of the PubMed to analyze quantitatively the publications in cancer and this information could be worthwhile in aiding the comprehension of some clinical aspects related with PC, as well as the development of preventative actions. The analysis of the scientific interest, considering the number of publications in the PubMed, reveals research trends in the field and demonstrates the importance of the surgical procedures in the treatment of the prostate cancer. Moreover, this finding is relevant due to the fact that surgery is the treatment of choice when early detection of PC is achieved. However, it is important to consider clinical complications related to such procedures, such as urinary incontinence and erectile dysfunctions that can reduce the quality of life of the patient

Laboratory-Evolved Mutants of an Exogenous Global Regulator, IrrE from Deinococcus radiodurans, Enhance Stress Tolerances of Escherichia coli

The tolerance of cells toward different stresses is very important for industrial strains of microbes, but difficult to improve by the manipulation of single genes. Traditional methods for enhancing cellular tolerances are inefficient and time-consuming. Recently, approaches employing global transcriptional or translational engineering methods have been increasingly explored. We found that an exogenous global regulator, irrE from an extremely radiation-resistant bacterium, Deinococcus radiodurans, has the potential to act as a global regulator in Escherichia coli, and that laboratory-evolution might be applied to alter this regulator to elicit different phenotypes for E. coli.To extend the methodology for strain improvement and to obtain higher tolerances toward different stresses, we here describe an approach of engineering irrE gene in E. coli. An irrE library was constructed by randomly mutating the gene, and this library was then selected for tolerance to ethanol, butanol and acetate stresses. Several mutants showing significant tolerances were obtained and characterized. The tolerances of E. coli cells containing these mutants were enhanced 2 to 50-fold, based on cell growth tests using different concentrations of alcohols or acetate, and enhanced 10 to 100-fold based on ethanol or butanol shock experiments. Intracellular reactive oxygen species (ROS) assays showed that intracellular ROS levels were sharply reduced for cells containing the irrE mutants. Sequence analysis of the mutants revealed that the mutations distribute cross all three domains of the protein.To our knowledge, this is the first time that an exogenous global regulator has been artificially evolved to suit its new host. The successes suggest the possibility of improving tolerances of industrial strains by introducing and engineering exogenous global regulators, such as those from extremophiles. This new approach can be applied alone or in combination with other global methods, such as global transcriptional machinery engineering (gTME) for strain improvements

Decreasing resection rates for nonmetastatic gastric cancer in Europe and the United States

Background: Resection is the cornerstone of curative treatment for many nonmetastatic gastric cancers (GCs), but the population treatment patterns remains largely unknown. This large international population-based study aimed at investigating the treatment patterns and trends for nonmetastatic GC in Europe and the United States and at exploring factors associated with resection. Methods: Data of patients with microscopically confirmed primary invasive GC without distant metastasis from the national cancer registries of the Netherlands, Belgium, Sweden, Norway, Slovenia, and Estonia and the US Surveillance, Epidemiology, and End Results (SEER)-18 Program were retrieved. Age-standardized treatment rates were computed and trends were evaluated using linear regression. Associations of resection with patient and tumor characteristics were analyzed using multivariable-adjusted log-binomial regression. Analysis was performed in each country respectively without pooling. Results: Together 65 707 nonmetastatic GC patients diagnosed in 2003-2016 were analyzed. Age-standardized resection rates significantly decreased over years in all countries (by 4-24%). In 2013-2014, rates varied greatly from 54 to 75%. Patients with increasing ages, cardia cancers, or cancers invading adjacent structure were significantly less frequently resected. Resection was further associated with sex, performance status, comorbidities, tumor histology, tumor size, hospital type, and hospital volume. Association patterns and strengths varied across countries. After multivariable adjustment, resection rates remained decreasing (prevalence ratio = 0.97-0.995 per year), with decreasing trends consistently seen in various subgroups. Conclusions: Nonmetastatic GCs were less frequently resected in Europe and the United States in the early 21st century. Resection rates varied greatly across countries and appeared not to be optimal. Various factors associated with resection were revealed. Our findings can help to identify differences and possibly modifiable places in clinical practice and provide important novel references for designing effective population-based GC management strategies. ∙ In Europe and the United States, nonmetastatic gastric cancers were less frequently resected in the early 21st century. ∙ Resection rates varied greatly across countries and appeared not optimal. ∙ Various factors associated with resection were revealed. ∙ Our findings identify differences and possibly modifiable places in clinical practice and provide important novel references for designing effective population-based management strategies

Assessment of Skeletal Muscle Contractile Properties by Radial Displacement: The Case for Tensiomyography

Skeletal muscle operates as a near-constant volume system; as such muscle shortening during contraction is transversely linked to radial deformation. Therefore, to assess contractile properties of skeletal muscle, radial displacement can be evoked and measured. Mechanomyography measures muscle radial displacement and during the last 20 years, tensiomyography has become the most commonly used and widely reported technique among the various methodologies of mechanomyography. Tensiomyography has been demonstrated to reliably measure peak radial displacement during evoked muscle twitch, as well as muscle twitch speed. A number of parameters can be extracted from the tensiomyography displacement/time curve and the most commonly used and reliable appear to be peak radial displacement and contraction time. The latter has been described as a valid non-invasive means of characterising skeletal muscle, based on fibre-type composition. Over recent years, applications of tensiomyography measurement within sport and exercise have appeared, with applications relating to injury, recovery and performance. Within the present review, we evaluate the perceived strengths and weaknesses of tensiomyography with regard to its efficacy within applied sports medicine settings. We also highlight future tensiomyography areas that require further investigation. Therefore, the purpose of this review is to critically examine the existing evidence surrounding tensiomyography as a tool within the field of sports medicine