Intertwined Functions of Separase and Caspase in Cell Division and Programmed Cell Death.

Timely sister chromatid separation, promoted by separase, is essential for faithful chromosome segregation. Separase is a member of the CD clan of cysteine proteases, which also includes the pro-apoptotic enzymes known as caspases. We report a role for the C. elegans separase SEP-1, primarily known for its essential activity in cell division and cortical granule exocytosis, in developmentally programmed cell death when the predominant pro-apoptotic caspase CED-3 is compromised. Loss of SEP-1 results in extra surviving cells in a weak ced-3(-) mutant, and suppresses the embryonic lethality of a mutant defective for the apoptotic suppressor ced-9/Bcl-2 implicating SEP-1 in execution of apoptosis. We also report apparent non-apoptotic roles for CED-3 in promoting germ cell proliferation, meiotic chromosome disjunction, egg shell formation, and the normal rate of embryonic development. Moreover, loss of the soma-specific (CSP-3) and germline-specific (CSP-2) caspase inhibitors result in CED-3-dependent suppression of embryonic lethality and meiotic chromosome non-disjunction respectively, when separase function is compromised. Thus, while caspases and separases have evolved different substrate specificities associated with their specialized functions in apoptosis and cell division respectively, they appear to have retained the residual ability to participate in both processes, supporting the view that co-option of components in cell division may have led to the innovation of programmed cell suicide early in metazoan evolution

Computer program simulates design, test, and analysis phases of sensitivity experiments

Modular program with a small main program and several specialized subroutines provides a general purpose computer program to simulate the design, test and analysis phases of sensitivity experiments. This program allows a wide range of design-response function combinations and the addition, deletion, or modification of subroutines

Medicare Reimbursement for Total Joint Arthroplasty: The Driving Forces.

BACKGROUND: Total joint arthroplasty is a large and growing part of the U.S. Medicare budget, drawing attention to how much providers are paid for their services. The purpose of this study was to examine the variables that affect total joint arthroplasty reimbursement. Along with standard economic variables, we include unique health-care variables. Given the focus on value in the Affordable Care Act, the model examines the relationship of the quality of care to total joint arthroplasty reimbursement. We hoped to find that reimbursement patterns reward quality and reflect standard economic principles. METHODS: Multivariable regression was performed to identify variables that correlate with Medicare reimbursement for total joint arthroplasty. Inpatient charge or reimbursement data on Medicare reimbursements were available for 2,750 hospitals with at least 10 discharges for uncomplicated total joint arthroplasty from the Centers for Medicare & Medicaid Services (CMS) for fiscal year 2011. Reimbursement variability was examined by using the Dartmouth Atlas to group institutions into hospital referral regions and hospital service areas. Independent variables were taken from the Dartmouth Atlas, CMS, the WWAMI (Washington, Wyoming, Alaska, Montana, Idaho) Rural Health Research Center, and the United States Census. RESULTS: There were 427,207 total joint arthroplasties identified, with a weighted mean reimbursement of $14,324.84 (range,$9,103 to $38,686). Nationally, the coefficient of variation for reimbursements was 0.19. The regression model accounted for 52.5% of reimbursement variation among providers. The total joint arthroplasty provider volume (p \u3c 0.001) and patient satisfaction (p \u3c 0.001) were negatively correlated with reimbursement. Government ownership of a hospital (p \u3c 0.001) and higher Medicare costs (p \u3c 0.001) correlated positively with reimbursement. CONCLUSIONS: Medicare reimbursements for total joint arthroplasty are highly variable. Greater reimbursement was associated with lower patient volume, lower patient satisfaction, a healthier patient population, and government ownership of a hospital. As value-based reimbursement provisions of the Affordable Care Act are implemented, there will be dramatic changes in total joint arthroplasty reimbursements. To meet these changes, providers should expect qualities such as high patient volume, willingness to care for sicker patient populations, patient satisfaction, safe outcomes, and procedural demand to correlate with their reimbursement. CLINICAL RELEVANCE: Practicing orthopaedic surgeons and hospital administrators should be aware of discrepancies in inpatient reimbursement for total joint arthroplasty from Medicare. Furthermore, these discrepancies are not associated with typical economic factors. These findings warrant further investigation and collaboration between policymakers and providers to develop value-based reimbursement

Instability of Extremal Relativistic Charged Spheres

With the question, ``Can relativistic charged spheres form extremal black holes?" in mind, we investigate the properties of such spheres from a classical point of view. The investigation is carried out numerically by integrating the Oppenheimer-Volkov equation for relativistic charged fluid spheres and finding interior Reissner-Nordstr\"om solutions for these objects. We consider both constant density and adiabatic equations of state, as well as several possible charge distributions, and examine stability by both a normal mode and an energy analysis. In all cases, the stability limit for these spheres lies between the extremal ($Q = M$) limit and the black hole limit ($R = R_+$). That is, we find that charged spheres undergo gravitational collapse before they reach $Q = M$, suggesting that extremal Reissner-Nordtr\"om black holes produced by collapse are ruled out. A general proof of this statement would support a strong form of the cosmic censorship hypothesis, excluding not only stable naked singularities, but stable extremal black holes. The numerical results also indicate that although the interior mass-energy $m(R)$ obeys the usual $m/R < 4/9$ stability limit for the Schwarzschild interior solution, the gravitational mass $M$ does not. Indeed, the stability limit approaches $R_+$ as $Q \to M$. In the Appendix we also argue that Hawking radiation will not lead to an extremal Reissner-Nordstr\"om black hole. All our results are consistent with the third law of black hole dynamics, as currently understood

GPRD, A Database for the Spectral Properties of Diatomic Molecules of Atmospheric Interest

A short note describing the development of a database providing factual and numerical data on the spectral properties of diatomic molecules. This database is available online for the overall scientific community at the following adress: http://cfp.ist.utl.pt/radiation/Comment: 2 page

Geometry of Valley Growth

Although amphitheater-shaped valley heads can be cut by groundwater flows emerging from springs, recent geological evidence suggests that other processes may also produce similar features, thus confounding the interpretations of such valley heads on Earth and Mars. To better understand the origin of this topographic form we combine field observations, laboratory experiments, analysis of a high-resolution topographic map, and mathematical theory to quantitatively characterize a class of physical phenomena that produce amphitheater-shaped heads. The resulting geometric growth equation accurately predicts the shape of decimeter-wide channels in laboratory experiments, 100-meter wide valleys in Florida and Idaho, and kilometer wide valleys on Mars. We find that whenever the processes shaping a landscape favor the growth of sharply protruding features, channels develop amphitheater-shaped heads with an aspect ratio of pi

Referencing Sources of Molecular Spectroscopic Data in the Era of Data Science: Application to the HITRAN and AMBDAS Databases

The application described has been designed to create bibliographic entries in large databases with diverse sources automatically, which reduces both the frequency of mistakes and the workload for the administrators. This new system uniquely identifies each reference from its digital object identifier (DOI) and retrieves the corresponding bibliographic information from any of several online services, including the SAO/NASA Astrophysics Data Systems (ADS) and CrossRef APIs. Once parsed into a relational database, the software is able to produce bibliographies in any of several formats, including HTML and BibTeX, for use on websites or printed articles. The application is provided free-of-charge for general use by any scientific database. The power of this application is demonstrated when used to populate reference data for the HITRAN and AMBDAS databases as test cases. HITRAN contains data that is provided by researchers and collaborators throughout the spectroscopic community. These contributors are accredited for their contributions through the bibliography produced alongside the data returned by an online search in HITRAN. Prior to the work presented here, HITRAN and AMBDAS created these bibliographies manually, which is a tedious, time-consuming and error-prone process. The complete code for the new referencing system can be found at \url{https://github.com/hitranonline/refs}.Comment: 11 pages, 5 figures, already published online at https://doi.org/10.3390/atoms802001

Effects of interdot dipole coupling in mesoscopic epitaxial Fe(100) dot arrays

The domain structure and the coercivity of epitaxial Fe(100) circular dot arrays of different diameters and separations have been studied using magnetic force microscopy (MFM) and focused magneto-optical Kerr effect (MOKE). The MFM images of the 1 µm diameter single domain dot arrays show direct evidence of strong interdot dipole coupling when the separation is reduced down to 0.1 µm. The coercivity of the dots is also found to be dependent on the separation, indicating the effect of the interdot dipole coupling on the magnetization reversal process

Two-dimensional hydrodynamic lattice-gas simulations of binary immiscible and ternary amphiphilic fluid flow through porous media

The behaviour of two dimensional binary and ternary amphiphilic fluids under flow conditions is investigated using a hydrodynamic lattice gas model. After the validation of the model in simple cases (Poiseuille flow, Darcy's law for single component fluids), attention is focussed on the properties of binary immiscible fluids in porous media. An extension of Darcy's law which explicitly admits a viscous coupling between the fluids is verified, and evidence of capillary effects are described. The influence of a third component, namely surfactant, is studied in the same context. Invasion simulations have also been performed. The effect of the applied force on the invasion process is reported. As the forcing level increases, the invasion process becomes faster and the residual oil saturation decreases. The introduction of surfactant in the invading phase during imbibition produces new phenomena, including emulsification and micellisation. At very low fluid forcing levels, this leads to the production of a low-resistance gel, which then slows down the progress of the invading fluid. At long times (beyond the water percolation threshold), the concentration of remaining oil within the porous medium is lowered by the action of surfactant, thus enhancing oil recovery. On the other hand, the introduction of surfactant in the invading phase during drainage simulations slows down the invasion process -- the invading fluid takes a more tortuous path to invade the porous medium -- and reduces the oil recovery (the residual oil saturation increases).Comment: 48 pages, 26 figures. Phys. Rev. E (in press