Acute effects of Vitamin D3 supplementation on muscle strength in Judoka athletes: a randomized placebo-controlled, double-blind trial

Objective: Indoor athletes have been shown to be prone to vitamin D3 deficiency. The aim of the study was to examine the acute effects of vitamin D supplementation on muscle function using isokinetic dynamometry. Design: Randomized placebo-controlled, double-blind study. Setting: Institutional. Participants: Adult male white national level judoka athletes (n = 22) who were involved in full-time training. Exclusion criteria were vitamin supplementation, overseas travel to sunny climes, and/or an injury incurred during the last 3 months before testing. Interventions: Subjects were randomly allocated to the treatment (150 000IU vitamin D3) or placebo and given blinded supplements by an independent researcher. Participants were tested twice, 8 days apart, on a Monday morning before the start of judo training and after 2 days of rest. A 5 to 7 mL of blood sample was collected followed by isokinetic concentric quadriceps and hamstring muscle function assessments on the right leg at 30 and 200°·s. Main outcome measures: Repeated-measures analysis of variance was used to analyze isokinetic muscle force and serum 25(OH)D3. Regression to the mean was used to examine changes in 25(OH)D3 levels over the study period. Results: The treatment group demonstrated a significant increase in serum 25(OH)D levels (34%, P ≤ 0.001) and muscle strength (13%, P = 0.01) between days 1 and 8. No significant differences were found for the placebo group for the same period. Conclusions: A single bolus of 150 000IU vitamin D3 had a significant positive effect on serum 25(OH)D levels and muscle function in vitamin D insufficient elite indoor athletes. Clinical relevance: Serum 25(OH)D3 levels of indoor athletes should be monitored throughout the year and especially during winter months. Beneficial responses, in muscle strength and serum 25(OH)D3, to 1 dose of vitamin D3 supplementation can be observed within 1 week of ingestion. Muscle strength is linked to serum 25(OH)D levels. Acute Effects of Vitamin D3 Supplementation on Muscle Strength in Judoka Athletes: A Randomized Placebo-Controlled, Double-Blind Trial (PDF Download Available). Available from: https://www.researchgate.net/publication/283499805_Acute_Effects_of_Vitamin_D3_Supplementation_on_Muscle_Strength_in_Judoka_Athletes_A_Randomized_Placebo-Controlled_Double-Blind_Trial [accessed May 10, 2016]

Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation.

Both adjuvants and focal ablation can alter the local innate immune system and trigger a highly effective systemic response. Our goal is to determine the impact of these treatments on directly treated and distant disease and the mechanisms for the enhanced response obtained by combinatorial treatments. Methods: We combined RNA-sequencing, flow cytometry and TCR-sequencing to dissect the impact of immunotherapy and of immunotherapy combined with ablation on local and systemic immune components. Results: With administration of a toll-like receptor agonist agonist (CpG) alone or CpG combined with same-site ablation, we found dramatic differences between the local and distant tumor environments, where the directly treated tumors were skewed to high expression of F4/80, Cd11b and Tnf and the distant tumors to enhanced Cd11c, Cd3 and Ifng. When ablation was added to immunotherapy, 100% (n=20/20) of directly treated tumors and 90% (n=18/20) of distant tumors were responsive. Comparing the combined ablation-immunotherapy treatment to immunotherapy alone, we find three major mechanistic differences. First, while ablation alone enhanced intratumoral antigen cross-presentation (up to ~8% of CD45+ cells), systemic cross-presentation of tumor antigen remained low. Combining same-site ablation with CpG amplified cross-presentation in the draining lymph node (~16% of CD45+ cells) compared to the ablation-only (~0.1% of CD45+ cells) and immunotherapy-only cohorts (~10% of CD45+ cells). Macrophages and DCs process and present this antigen to CD8+ T-cells, increasing the number of unique T-cell receptor rearrangements in distant tumors. Second, type I interferon (IFN) release from tumor cells increased with the ablation-immunotherapy treatment as compared with ablation or immunotherapy alone. Type I IFN release is synergistic with toll-like receptor activation in enhancing cytokine and chemokine expression. Expression of genes associated with T-cell activation and stimulation (Eomes, Prf1 and Icos) was 27, 56 and 89-fold higher with ablation-immunotherapy treatment as compared to the no-treatment controls (and 12, 32 and 60-fold higher for immunotherapy-only treatment as compared to the no-treatment controls). Third, we found that the ablation-immunotherapy treatment polarized macrophages and dendritic cells towards a CD169 subset systemically, where CD169+ macrophages are an IFN-enhanced subpopulation associated with dead-cell antigen presentation. Conclusion: While the local and distant responses are distinct, CpG combined with ablative focal therapy drives a highly effective systemic immune response

Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma

Head and neck cell squamous-cell carcinomas (HNSCC) are a group of common cancers typically associated with tobacco use and human papilloma virus infection. Up to half of all cases will suffer a recurrence after primary treatment. As such, new therapies are needed, including therapies which promote the anti-tumor immune response. Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution. We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified from the Washington University tumor bank. Whole exosome sequencing, RNA-seq, and immunohistochemistry was performed on the primary and recurrent tumors. Within these tumors, we identified 6 genes which have predicted neoantigens in 4 or more patients. Interestingly, patients with neoantigens in these shared genes had increased CD3+ CD8+ T cell infiltration and duration of survival with disease. Within HNSCC tumors examined here, there are neoantigens in shared genes by a subset of patients. The presence of neoantigens in these shared genes may promote an anti-tumor immune response which controls tumor progression

Real-Time Projection to Verify Plan Success During Execution

The Mission Data System provides a framework for modeling complex systems in terms of system behaviors and goals that express intent. Complex activity plans can be represented as goal networks that express the coordination of goals on different state variables of the system. Real-time projection extends the ability of this system to verify plan achievability (all goals can be satisfied over the entire plan) into the execution domain so that the system is able to continuously re-verify a plan as it is executed, and as the states of the system change in response to goals and the environment. Previous versions were able to detect and respond to goal violations when they actually occur during execution. This new capability enables the prediction of future goal failures; specifically, goals that were previously found to be achievable but are no longer achievable due to unanticipated faults or environmental conditions. Early detection of such situations enables operators or an autonomous fault response capability to deal with the problem at a point that maximizes the available options. For example, this system has been applied to the problem of managing battery energy on a lunar rover as it is used to explore the Moon. Astronauts drive the rover to waypoints and conduct science observations according to a plan that is scheduled and verified to be achievable with the energy resources available. As the astronauts execute this plan, the system uses this new capability to continuously re-verify the plan as energy is consumed to ensure that the battery will never be depleted below safe levels across the entire plan

A short proof of stability of topological order under local perturbations

Recently, the stability of certain topological phases of matter under weak perturbations was proven. Here, we present a short, alternate proof of the same result. We consider models of topological quantum order for which the unperturbed Hamiltonian $H_0$ can be written as a sum of local pairwise commuting projectors on a $D$-dimensional lattice. We consider a perturbed Hamiltonian $H=H_0+V$ involving a generic perturbation $V$ that can be written as a sum of short-range bounded-norm interactions. We prove that if the strength of $V$ is below a constant threshold value then $H$ has well-defined spectral bands originating from the low-lying eigenvalues of $H_0$. These bands are separated from the rest of the spectrum and from each other by a constant gap. The width of the band originating from the smallest eigenvalue of $H_0$ decays faster than any power of the lattice size.Comment: 15 page

What clinical trials are needed for treatment of leiomyosarcoma?

Leiomyosarcoma is one of the most common subtypes of soft tissue sarcomas accounting for approximately 20% of sarcomas. As leiomyosarcoma patients frequently develop metastatic disease, effective systemic therapies are needed to improve clinical outcomes. The overall activity of the currently available conventional systemic therapies and the prognosis of patients with advanced and/or metastatic disease are poor. As such, the treatment of this patient population remains challenging. As a result, there is a clear unmet medical need, and designing and performing meaningful clinical studies are of utmost importance to improve the prognosis of this patient group. Therefore, the aim of this review is to briefly summarize state-of-the-art treatments for leiomyosarcoma patients and to describe trial characteristics needed for informative clinical studies

PASCal: A principal-axis strain calculator for thermal expansion and compressibility determination

We describe a web-based tool (PASCal; Principal Axis Strain Calculator) aimed at simplifying the determination of principal coefficients of thermal expansion and compressibilities from variable-temperature and variable-pressure lattice parameter data. In a series of three case studies, we use PASCal to re-analyse previously-published lattice parameter data and show that additional scientific insight is obtainable in each case. First, the two-dimensional metal-organic framework Cu-SIP-3 is found to exhibit the strongest area-negative thermal expansion (NTE) effect yet observed; second, the widely-used explosive HMX exhibits much stronger mechanical anisotropy than had previously been anticipated, including uniaxial NTE driven by thermal changes in molecular conformation; and, third, the high-pressure form of the mineral malayaite is shown to exhibit a strong negative linear compressibility (NLC) effect that arises from correlated tilting of SnO6 and SiO4 coordination polyhedra.Comment: 31 pages, 8 figures, formatted as preprint for J. Appl. Crys

Microarray and deep sequencing cross-platform analysis of the mirRNome and isomiR variation in response to epidermal growth factor

BACKGROUND: Epidermal Growth Factor (EGF) plays an important function in the regulation of cell growth, proliferation, and differentiation by binding to its receptor (EGFR) and providing cancer cells with increased survival responsiveness. Signal transduction carried out by EGF has been extensively studied at both transcriptional and post-transcriptional levels. Little is known about the involvement of microRNAs (miRNAs) in the EGF signaling pathway. miRNAs have emerged as major players in the complex networks of gene regulation, and cancer miRNA expression studies have evidenced a direct involvement of miRNAs in cancer progression. RESULTS: In this study, we have used an integrative high content analysis approach to identify the specific miRNAs implicated in EGF signaling in HeLa cells as potential mediators of cancer mediated functions. We have used microarray and deep-sequencing technologies in order to obtain a global view of the EGF miRNA transcriptome with a robust experimental cross-validation. By applying a procedure based on Rankprod tests, we have delimited a solid set of EGF-regulated miRNAs. After validating regulated miRNAs by reverse transcription quantitative PCR, we have derived protein networks and biological functions from the predicted targets of the regulated miRNAs to gain insight into the potential role of miRNAs in EGF-treated cells. In addition, we have analyzed sequence heterogeneity due to editing relative to the reference sequence (isomiRs) among regulated miRNAs. CONCLUSIONS: We propose that the use of global genomic miRNA cross-validation derived from high throughput technologies can be used to generate more reliable datasets inferring more robust networks of co-regulated predicted miRNA target genes