Displaying Properties of PDFs

PDFVis is a computer program that assists in visualization of uncertainty as represented by a probability density function (PDF) located at each grid cell in a spatial domain. The functions that PDFV performs are listed

A role for the histone deacetylase HDAC4 in the life-cycle of HIV-1-based vectors

HIV-1 integration is mediated by the HIV-1 integrase protein, which joins 3'-ends of viral DNA to host cell DNA. To complete the integration process, HIV-1 DNA has to be joined to host cell DNA also at the 5'-ends. This process is called post-integration repair (PIR). Integration and PIR involve a number of cellular co-factors. These proteins exhibit different degrees of involvement in integration and/or PIR. Some are required for efficient integration or PIR. On the other hand, some reduce the efficiency of integration. Finally, some are involved in integration site selection. We have studied the role of the histone deacetylase HDAC4 in these processes. HDAC4 was demonstrated to play a role in both cellular double-strand DNA break repair and transcriptional regulation. We observed that HDAC4 associates with viral DNA in an integrase-dependent manner. Moreover, infection with HIV-1-based vectors induces foci of the HDAC4 protein. The related histone deacetylases, HDAC2 and HDAC6, failed to associate with viral DNA after infection. These data suggest that HDAC4 accumulates at integration sites. Finally, overexpression studies with HDAC4 mutants suggest that HDAC4 may be required for efficient transduction by HIV-1-based vectors in cells that are deficient in other DNA repair proteins. We conclude that HDAC4 is likely involved in PIR

ML-MEDIC: A Preliminary Study of an Interactive Visual Analysis Tool Facilitating Clinical Applications of Machine Learning for Precision Medicine

Accessible interactive tools that integrate machine learning methods with clinical research and reduce the programming experience required are needed to move science forward. Here, we present Machine Learning for Medical Exploration and Data-Inspired Care (ML-MEDIC), a point-and-click, interactive tool with a visual interface for facilitating machine learning and statistical analyses in clinical research. We deployed ML-MEDIC in the American Heart Association (AHA) Precision Medicine Platform to provide secure internet access and facilitate collaboration. ML-MEDIC’s efficacy for facilitating the adoption of machine learning was evaluated through two case studies in collaboration with clinical domain experts. A domain expert review was also conducted to obtain an impression of the usability and potential limitations

Contact structures in the poultry industry in Great Britain: Exploring transmission routes for a potential avian influenza virus epidemic

Background: The commercial poultry industry in United Kingdom (UK) is worth an estimated £3.4 billion at retail value, producing over 174 million birds for consumption per year. An epidemic of any poultry disease with high mortality or which is zoonotic, such as avian influenza virus (AIV), would result in the culling of significant numbers of birds, as seen in the Netherlands in 2003 and Italy in 2000. Such an epidemic would cost the UK government millions of pounds in compensation costs, with further economic losses through reduction of international and UK consumption of British poultry. In order to better inform policy advisers and makers on the potential for a large epidemic in GB, we investigate the role that interactions amongst premises within the British commercial poultry industry could play in promoting an AIV epidemic, given an introduction of the virus in a specific part of poultry industry in Great Britain (GB). Results: Poultry premises using multiple slaughterhouses lead to a large number of premises being potentially connected, with the resultant potential for large and sometimes widespread epidemics. Catching companies can also potentially link a large proportion of the poultry population. Critical to this is the maximum distance traveled by catching companies between premises and whether or not between-species transmission could occur within individual premises. Premises closely linked by proximity may result in connections being formed between different species and or sectors within the industry. Conclusion: Even quite well-contained epidemics have the potential for geographically widespread dissemination, potentially resulting in severe logistical problems for epidemic control, and with economic impact on a large part of the country. Premises sending birds to multiple slaughterhouses or housing multiple species may act as a bridge between otherwise separate sectors of the industry, resulting in the potential for large epidemics. Investment into further data collection and analyses on the importance of industry structure as a determinant for spread of AIV would enable us to use the results from this study to contribute to policy on disease control

Loan initiation and audit pricing

We examine the effect of lenders’ certification for pricing of auditing services for the borrowers. We find that audit fees decrease after obtaining a new loan from banks, suggesting that banks’ certification of firms’ future performance has decreased auditors’ perceived risks associated with their clients. Furthermore, we show that the certification effect is stronger among firms associated with higher ex ante risk measured by ex ante leverage and cash-flow volatility. Our study contributes to both auditing and banking literature by documenting that lenders’ certification has significant impact on one of the important capital market participants, auditors

Skeletal disproportion in glucocorticoid-treated boys with Duchenne muscular dystrophy

We aimed to compare body segment and bone lengths in glucocorticoid-treated boys with Duchenne muscular dystrophy (DMD) with healthy controls using dual-energy absorptiometry (DXA) images. Total height (Ht), sitting height (SH), leg length (LL) and bone lengths (femur, tibia) in boys with DMD and age-matched control boys were measured using DXA. Thirty boys with DMD (median age 10.0 years (6.1, 16.8)) were compared with 30 controls. SH in DMD was 3.3 cm lower (95% CI − 6.1, − 0.66; p = 0.016). LL in DMD was 7.3 cm lower (95% CI − 11.2, − 3.4; p < 0.0001). SH:LL of boys with DMD was higher by 0.08 (95% CI 0.04, 0.12; p < 0.0001). Femur length in DMD was 2.4 cm lower (95% CI − 4.6, − 0.12; p = 0.04), whereas tibial length in DMD was 4.8 cm lower (95% CI − 6.7, − 2.9; p < 0.0001). SH:LL was not associated with duration of glucocorticoid use (SH:LL β = 0.003, 95% CI − 0.01 to 0.002, p = 0.72). Conclusion: Glucocorticoid-treated boys with DMD exhibit skeletal disproportion with relatively shorter leg length and more marked reduction of distal long bones. As glucocorticoid excess is not associated with such disproportion, our findings raise the possibility of an intrinsic disorder of growth in DMD

Recurrent MEIS1-NCOA2/1 fusions in a subset of low-grade spindle cell sarcomas frequently involving the genitourinary and gynecologic tracts

Sarcomas with MEIS1-NCOA2 fusions have been so far reported in 2 cases each of primitive renal sarcomas and intraosseous pelvic rhabdomyosarcomas. Their histologic spectrum, anatomic distribution, and clinical behavior remain poorly defined. In this study, we report 6 additional spindle cell sarcomas with MEIS1-NCOA2 or NCOA1 fusions that fall into the same disease spectrum with the previously reported renal sarcomas. The patients’ age range was wide (20–76 years, mean 46) and all except one were female. The tumors arose in the kidney (n=2), and one each in the uterine corpus, vagina, scrotum, and para-rectal region. The consistent morphology was that of monomorphic spindle to ovoid cells in a storiform, whorling, or solid pattern. Alternating cellularity, myxoid stroma, and microcystic changes were seen in some cases. Mitotic activity varied greatly (<1–33/10 high power fields). The immunophenotype was non-specific, with most cases expressing variable degrees of TLE1, WT1, cyclin D1, CD56, and CD10. Using various platforms of RNA-based targeted sequencing, MEIS1-NCOA2 fusions were recurrently identified in 5 cases, and a novel MEIS1-NCOA1 fusion was found in one renal tumor. The gene fusions were validated by fluorescence in situ hybridization using custom BAC probes. Of the 5 patients with available follow-up (5 months to 8 years), all experienced local recurrences, but no distant spread or death from disease. Our results expand the clinicopathologic spectrum of sarcomas with MEIS1-NCOA2/1 fusions, providing evidence of an undifferentiated spindle cell phenotype with non-specific immunoprofile and low-grade clinical behavior

Mobility of Taxol in Microtubule Bundles

Mobility of taxol inside microtubules was investigated using fluorescence recovery after photobleaching (FRAP) on flow-aligned bundles. Bundles were made of microtubules with either GMPCPP or GTP at the exchangeable site on the tubulin dimer. Recovery times were sensitive to bundle thickness and packing, indicating that taxol molecules are able to move laterally through the bundle. The density of open binding sites along a microtubule was varied by controlling the concentration of taxol in solution for GMPCPP samples. With > 63% sites occupied, recovery times were independent of taxol concentration and, therefore, inversely proportional to the microscopic dissociation rate, k_{off}. It was found that 10*k_{off} (GMPCPP) ~ k_{off} (GTP), consistent with, but not fully accounting for, the difference in equilibrium constants for taxol on GMPCPP and GTP microtubules. With < 63% sites occupied, recovery times decreased as ~ [Tax]^{-1/5} for both types of microtubules. We conclude that the diffusion of taxol along the microtubule interior is hindered by rebinding events when open sites are within ~7 nm of each other.Comment: pre print forma