Advances in Glucocorticoid-Induced Osteoporosis

Glucocorticoid-induced osteoporosis (GIOP) is one of the most important side effects of glucocorticoid use, as it leads to an increased risk of fractures. Recently, many published studies have focused on the cellular and molecular mechanisms of bone metabolism, the pathophysiology of GIOP, and the intervention options to prevent GIOP. In this review, recent advances in GIOP are summarized, particularly recent progress in our understanding of the mechanisms of GIOP resulting in improved insight that might result in the development of new treatment options in the near future

The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function

Shortening and removal of the polyadenylate [poly(A)] tail of mRNA, a process called deadenylation, is a key step in mRNA decay that is mediated through the CCR4-NOT (carbon catabolite repression 4-negative on TATA-less) complex. In our investigation of the regulation of mRNA deadenylation in the heart, we found that this complex was required to prevent cell death. Conditional deletion of the CCR4-NOT complex components Cnot1 or Cnot3 resulted in the formation of autophagic vacuoles and cardiomyocyte death, leading to lethal heart failure accompanied by long QT intervals. Cnot3 bound to and shortened the poly(A) tail of the mRNA encoding the key autophagy regulator Atg7. In Cnot3-depleted hearts, Atg7 expression was posttranscriptionally increased. Genetic ablation of Atg7, but not Atg5, increased survival and partially restored cardiac function of Cnot1 or Cnot3 knockout mice. We further showed that in Cnot3-depleted hearts, Atg7 interacted with p53 and modulated p53 activity to induce the expression of genes encoding cell death-promoting factors in cardiomyocytes, indicating that defects in deadenylation in the heart aberrantly activated Atg7 and p53 to promote cell death. Thus, mRNA deadenylation mediated by the CCR4-NOT complex is crucial to prevent Atg7-induced cell death and heart failure, suggesting a role for mRNA deadenylation in targeting autophagy genes to maintain normal cardiac homeostasis

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Calcium Reduction of TiS2 in CaCl2 Melt

In this study, we reduce TiS2 to Ti via both calciothermic reduction and electrolysis in a CaCl2 melt. Upon calcium reduction at 1133 K in CaCl2 melt, the concentration of sulfur decreases to 0.03 mass% S when an amount greater than twice the stoichiometric calcium amount is added. Upon electrolysis reduction at 1173 K in CaCl2-CaS melt, the concentration of sulfur initially decreases significantly to 0.01 mass% S when a sufficiently large amount of electric charge is supplied. Our results indicate that it is possible to achieve sulfur removal via both calciothermic reduction and electrochemical reaction

A rapidly mixing approximate sampler of Dirichlet distribution

In this paper, we propose a Markov chain for sampling a random variable distributed according to a discretized Dirichlet distribution. We show that our Markov chain is rapidly mixing, that is, the mixing time of our chain is (1/2)n(n-1)1n((Δ－ｎ)ε＾＜－1＞)　where n is the dimension (the number of parameters), 1/Δ is the grid size for discretization, and εis the error bound. We estimate the mixing time by using the path coupling method. When the parameters are large, the log-concavity of the density function implies the rapidity straight forwardly. In the case that parameters are small, the density function is convex and so we need a different approach to use the path coupling method. We also show the rate of convergence of our chain experimentally

Hot-Wire Study On The Impact Of Porous Structure On Mean And Turbulent Velocity Profiles In The Near-Field Of A High Aspect Ratio Porous Filled Slot Jet

A 2-D rectangular slot jet (AR=61) with a porous blockage is experimentally tested for mean velocity and turbulence profiles in the near field. Porosities of the blockages tested are nominally 0, 0.40, 0.50, and 0.60, all crushed aluminum foam. The presence of the porous blockage can be seen in the deformed mean profile and in the lower magnitudes of turbulence intensity. The porous blockage acts to change the relevant length scale to that more on the order of the pore size rather than the slot width. Using a method meant for standardizing the turbulent length scale calculation, a length scale for each case is calculated and found to vary weakly with respect to porosity. The three length scales are calculated for each case and are compared. The length scale based on the zero frequency extrapolation of the power spectral density gave the most reasonable results. Adiabatic film cooling effectiveness values are given for three blowing ratios for the 0.60 porosity insert. Film effectiveness is seen to increase with mass injected over the entire test surface. © 2011 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved