Scattering of underwater sound from a porous solid sphere

An experiment was performed to measure the scattering of underwater sound from a porous solid for the first time. Two porous solid spheres somposed of heat-epoxied glass beads of 100 and 500 micron mean bead diameter were used. The permeability, porosity, and shear modulus of each sample were estimated from measurements made on cylindrical samples which had been manufactured at the same time and of the same glass beads as the spheres. These material poperties were used as input to a theoretical model for the sound scattered from a poro-elastic sphere imbedded in a poro-elastic host developed by Kargl and Lim. The experimental data were compared to the theoretical calculations. Theoretical calculations with 0%, 3%, and 10% skeletal fram damping were compared to experimental data. Very good agreement between measured and predicted scattering was obtained for each sample over certain frequency ranges, taking 10% fram damping in the calculations. For other frequency ranges the agreement was less than good. No systematic trend in the agreement could be discerned with regard to prous grain size or sound frequencyhttp://archive.org/details/scatteringofunde00huskLieutenant, United States NavyApproved for public release; distribution is unlimited

A Comprehensive Residency Wellness Curriculum

Introduction: Resident physician burnout is an epidemic in medical education. There are several wellness curricula published, but few describe a comprehensive program to address wellness. Our objectives were to develop and pilot a longitudinal resident wellness curriculum and assess for feasibility and sustainability. Methods: We surveyed emergency medicine (EM) residents from two residency programs in the United States to assess a baseline level of burnout using the Maslach Burnout Inventory. We developed a comprehensive and longitudinal wellness curriculum for EM residents that incorporated all domains identified by the American College of Emergency Physicians Wellness Wheel. Mindfulness practice was incorporated throughout the curriculum. Results: A convenience sample of 106 EM residents were sent the baseline survey. A response rate of 69% was achieved, the median age of the respondents was 29 years, and 44.5% were female. Overall, 67.5% (95% CI: 50.5; 80.8%) reported burnout in at least one of the three domains of the Maslach Burnout inventory. 34.8% reported burnout in the personal accomplishment domain, 40.8% reported depersonalization, and 44.3% reported emotional exhaustion. The wellness curriculum was successfully implemented at the Georgia-based residency program. The curriculum has proven to be sustainable since it began in 2016. Quantitative statistical testing for the post-intervention survey was not possible due to a low response rate. However, subjective receivability was high, with participants describing these sessions as high-yield, informative and practical. Conclusions: Burnout is highly prevalent among EM residents. We provide a curriculum developed for an EM residency program that is multifaceted and comprehensive, including basic wellness topics, mindfulness, financial and medicolegal issues, as well as topics that address the stresses specific to clinical emergency medicine. The curriculum has been in place in its current form since 2016 and has proven to be sustainable

Long QT Syndrome Type 2: Emerging Strategies for Correcting Class 2 \u3cem\u3eKCNH2 (hERG)\u3c/em\u3e Mutations and Identifying New Patients

Significant advances in our understanding of the molecular mechanisms that cause congenital long QT syndrome (LQTS) have been made. A wide variety of experimental approaches, including heterologous expression of mutant ion channel proteins and the use of inducible pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from LQTS patients offer insights into etiology and new therapeutic strategies. This review briefly discusses the major molecular mechanisms underlying LQTS type 2 (LQT2), which is caused by loss-of-function (LOF) mutations in the KCNH2 gene (also known as the human ether-à-go-go-related gene or hERG). Almost half of suspected LQT2-causing mutations are missense mutations, and functional studies suggest that about 90% of these mutations disrupt the intracellular transport, or trafficking, of the KCNH2-encoded Kv11.1 channel protein to the cell surface membrane. In this review, we discuss emerging strategies that improve the trafficking and functional expression of trafficking-deficient LQT2 Kv11.1 channel proteins to the cell surface membrane and how new insights into the structure of the Kv11.1 channel protein will lead to computational approaches that identify which KCNH2 missense variants confer a high-risk for LQT2

Myofilament Calcium Sensitivity: Consequences of the Effective Concentration of Troponin I

Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to bind the switch peptide region of TnI. Considering TnI is essentially tethered to TnC and cannot diffuse away in the absence of calcium, we suggest that the apparent calcium binding properties of TnC are highly dependent upon an “effective concentration” of TnI available to bind TnC. Based on our previous work, TnI peptide binding studies and the calcium binding properties of chimeric TnC-TnI fusion constructs, and building upon the concept of effective concentration, we have developed a mathematical model that can simulate the steady-state and kinetic calcium binding properties of a wide assortment of disease-related and post-translational protein modifications in the isolated troponin complex and reconstituted thin filament. We predict that several TnI and TnT modifications do not alter any of the intrinsic calcium or TnI binding constants of TnC, but rather alter the ability of TnC to “find” TnI in the presence of calcium. These studies demonstrate the apparent consequences of the effective TnI concentration in modulating the calcium binding properties of TnC

Localized practices and globalized futures: challenges for Alaska coastal community youth

An article from Maritime Studies (2015) 14:

The Novel Immunosuppressive Protein Kinase C Inhibitor Sotrastaurin Has No Pro-Viral Effects on the Replication Cycle of Hepatitis B or C Virus

The pan-protein kinase C (PKC) inhibitor sotrastaurin (AEB071) is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV), major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients

The Vicious Circle of Post-Soviet Neopatrimonialism in Russia

Published online: 10 Aug 2015, journal issue (vol.32, N5) appeared in 2016Since the collapse of Communism, Russia and some other post-Soviet states have attempted to pursue socio-economic reforms while relying upon the political institutions of neopatrimonialism. This politico-economic order was established to serve the interests of ruling groups and establish the major features of states, political regimes, and market economies. It provided numerous negative incentives for governing the economy and the state due to the unconstrained rent seeking behavior of major actors. Policy reform programs discovered these institutions to be incompatible with the priorities of modernization, and efforts to resolve these contradictions through a number of partial and compromise solutions often worsened the situation vis-à-vis preservation of the status quo. The ruling groups lack incentives for institutional changes, which could undermine their political and economic dominance, and are caught in a vicious circle: reforms often result in minor returns or cause unintended and undesired consequences. What are the possible domestic and international incentives to reject the political institutions of neopatrimonialism in post-Soviet states and replace them with inclusive economic and political ones?Peer reviewe

Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026

In this study we investigated the in vitro time dependence of radiosensitisation, pharmacokinetics and metabolism of NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). At a dose of 10 μM, which is nontoxic to cells per se, a minimum NU7026 exposure of 4 h in combination with 3 Gy radiation is required for a significant radiosensitisation effect in CH1 human ovarian cancer cells. Following intravenous administration to mice at 5 mg kg−1, NU7026 underwent rapid plasma clearance (0.108 l h−1) and this was largely attributed to extensive metabolism. Bioavailability following interperitoneal (i.p.) and p.o. administration at 20 mg kg−1 was 20 and 15%, respectively. Investigation of NU7026 metabolism profiles in plasma and urine indicated that the compound undergoes multiple hydroxylations. A glucuronide conjugate of a bis-hydroxylated metabolite represented the major excretion product in urine. Identification of the major oxidation site as C-2 of the morpholine ring was confirmed by the fact that the plasma clearance of NU7107 (an analogue of NU7026 methylated at C-2 and C-6 of the morpholine ring) was four-fold slower than that of NU7026. The pharmacokinetic simulations performed predict that NU7026 will have to be administered four times per day at 100 mg kg−1 i.p. in order to obtain the drug exposure required for radiosensitisation