Multilevel Parallelization of AutoDock 4.2

<p>Abstract</p> <p>Background</p> <p>Virtual (computational) screening is an increasingly important tool for drug discovery. AutoDock is a popular open-source application for performing molecular docking, the prediction of ligand-receptor interactions. AutoDock is a serial application, though several previous efforts have parallelized various aspects of the program. In this paper, we report on a multi-level parallelization of AutoDock 4.2 (mpAD4).</p> <p>Results</p> <p>Using MPI and OpenMP, AutoDock 4.2 was parallelized for use on MPI-enabled systems and to multithread the execution of individual docking jobs. In addition, code was implemented to reduce input/output (I/O) traffic by reusing grid maps at each node from docking to docking. Performance of mpAD4 was examined on two multiprocessor computers.</p> <p>Conclusions</p> <p>Using MPI with OpenMP multithreading, mpAD4 scales with near linearity on the multiprocessor systems tested. In situations where I/O is limiting, reuse of grid maps reduces both system I/O and overall screening time. Multithreading of AutoDock's Lamarkian Genetic Algorithm with OpenMP increases the speed of execution of individual docking jobs, and when combined with MPI parallelization can significantly reduce the execution time of virtual screens. This work is significant in that mpAD4 speeds the execution of certain molecular docking workloads and allows the user to optimize the degree of system-level (MPI) and node-level (OpenMP) parallelization to best fit both workloads and computational resources.</p

Implementation of a software application for presurgical case history review of frozen section pathology cases

Background: The frozen section pathology practice at Mayo Clinic in Rochester performs ~20,000 intraoperative consultations a year (~70–80/weekday). To prepare for intraoperative consultations, surgical pathology fellows and residents review the case history, previous pathology, and relevant imaging the day before surgery. Before the work described herein, review of pending surgical pathology cases was a paper-based process requiring handwritten transcription from the electronic health record, a laborious and potentially error prone process. Methods: To facilitate more efficient case review, a modular extension of an existing surgical listing software application (Surgical and Procedure Scheduling [SPS]) was developed. The module (SPS-pathology-specific module [PM]) added pathology-specific functionality including recording case notes, prefetching of radiology, pathology, and operative reports from the medical record, flagging infectious cases, and real-time tracking of cases in the operating room. After implementation, users were surveyed about its impact on the surgical pathology practice. Results: There were 16 survey respondents (five staff pathologists and eleven residents or fellows). All trainees (11/11) responded that the application improved an aspect of surgical list review including abstraction from medical records (10/11), identification of possibly infectious cases (7/11), and speed of list preparation (10/11). The average reported time savings in list preparation was 1.4 h/day. Respondents indicated the application improved the speed (11/16), clarity (13/16), and accuracy (10/16) of morning report. During the workday, respondents reported the application improved real-time case review (14/16) and situational awareness of ongoing cases (13/16). Conclusions: A majority of respondents found the SPS-PM improved all preparatory and logistical aspects of the Mayo Clinic frozen section surgical pathology practice. In addition, use of the SPS-PM saved an average of 1.4 h/day for residents and fellows engaged in preparatory case review

ESCRT-independent budding of HIV-1 gag virus-like particles from Saccharomyces cerevisiae spheroplasts.

Heterologous expression of HIV-1 Gag in a variety of host cells results in its packaging into virus-like particles (VLPs) that are subsequently released into the extracellular milieu. This phenomenon represents a useful tool for probing cellular factors required for viral budding and has contributed to the discovery of roles for ubiquitin ligases and the endosomal sorting complexes required for transport (ESCRTs) in viral budding. These factors are highly conserved throughout eukaryotes and have been studied extensively in the yeast Saccharomyces cerevisiae, a model eukaryote previously utilized as a host for the production of VLPs. We used heterologous expression of HIV Gag in yeast spheroplasts to examine the role of ESCRTs and associated factors (Rsp5, a HECT ubiquitin ligase of the Nedd4 family; Bro1, a homolog of Alix; and Vps4, the AAA-ATPase required for ESCRT function in all contexts/organisms investigated) in the generation of VLPs. Our data reveal: 1) characterized Gag-ESCRT interaction motifs (late domains) are not required for VLP budding, 2) loss of function alleles of the essential HECT ubiquitin ligase Rsp5 do not display defects in VLP formation, and 3) ESCRT function is not required for VLP formation from spheroplasts. These results suggest that the egress of HIV Gag from yeast cells is distinct from the most commonly described mode of exit from mammalian cells, instead mimicking ESCRT-independent VLP formation observed in a subset of mammalian cells. As such, budding of Gag from yeast cells appears to represent ESCRT-independent budding relevant to viral replication in at least some situations. Thus the myriad of genetic and biochemical tools available in the yeast system may be of utility in the study of this aspect of viral budding

Toto, we’re not in Kansas anymore: First reported case of M. persicum septic arthritis

In this report, we describe a case of septic arthritis caused by the newly described Mycobacterium persicum (formerly Mycobacterium kansasii complex). The patient's only significant exposure was home gardening. To our knowledge, this represents the first documented case of M. persicum infection in the United States and first septic arthritis