Complex workflows consisting of multiple simulation and analysis codes running concurrently through in-memory coupling is becoming popular due to inherent advantages in online management of ...large-scale data, resilience, and the code development process. However, orchestrating such a multi-application workflow to efficiently utilize resources on a heterogeneous architecture is challenging. In this paper, we present our results with running the Fusion Whole Device Modeling benchmark workflow on Summit, a pre-exascale supercomputer at Oak Ridge National Laboratory. We explore various resource distribution and process placement mechanisms, including sharing compute nodes between processes from separate applications. We show that fine-grained process placement can have a significant impact towards efficient utilization of the compute power of a node on Summit, and conclude that sophisticated tools for performing co-design studies of multi-application workflows can play an important role towards efficient orchestration of such workflows.
Scientific workflows have been used almost universally across scientific domains, and have underpinned some of the most significant discoveries of the past several decades. Many of these workflows ...have high computational, storage, and/or communication demands, and thus must execute on a wide range of large-scale platforms, from large clouds to upcoming exascale high-performance computing (HPC) platforms. These executions must be managed using some software infrastructure. Due to the popularity of workflows, workflow management systems (WMSs) have been developed to provide abstractions for creating and executing workflows conveniently, efficiently, and portably. While these efforts are all worthwhile, there are now hundreds of independent WMSs, many of which are moribund. As a result, the WMS landscape is segmented and presents significant barriers to entry due to the hundreds of seemingly comparable, yet incompatible, systems that exist. As a result, many teams, small and large, still elect to build their own custom workflow solution rather than adopt, or build upon, existing WMSs. This current state of the WMS landscape negatively impacts workflow users, developers, and researchers. The "Workflows Community Summit" was held online on January 13, 2021. The overarching goal of the summit was to develop a view of the state of the art and identify crucial research challenges in the workflow community. Prior to the summit, a survey sent to stakeholders in the workflow community (including both developers of WMSs and users of workflows) helped to identify key challenges in this community that were translated into 6 broad themes for the summit, each of them being the object of a focused discussion led by a volunteer member of the community. This report documents and organizes the wealth of information provided by the participants before, during, and after the summit.
HDF5 is a data model, library and file format for storing and managing data. It is designed for flexible and efficient I/O for high volume and complex data. Natively, it uses a single-file format ...where multiple HDF5 objects are stored in a single file. In a parallel HDF5 application, multiple processes access a single file, thereby resulting in a performance bottleneck in I/O. Additionally, a single-file format does not allow semantic post processing on individual objects outside the scope of the HDF5 application. We have developed a new plugin for HDF5 using its Virtual Object Layer that serves two purposes: 1) it uses PLFS to convert the single-file layout into a data layout that is optimized for the underlying file system, and 2) it stores data in a unique way that enables semantic post-processing on data. We measure the performance of the plugin and discuss work leveraging the new semantic post-processing functionality enabled. We further discuss the applicability of this approach for exascale burst buffer storage systems.
Pancreatic ductal adenocarcinomas (PDACs) are highly aggressive malignancies, associated with poor clinical prognosis and limited therapeutic options. Oncogenic
mutations are found in over 90% of ...PDACs, playing a central role in tumor progression. Global gene expression profiling of PDAC reveals 3-4 major molecular subtypes with distinct phenotypic traits and pharmacological vulnerabilities, including variations in oncogenic KRAS pathway dependencies. PDAC cell lines of the aberrantly differentiated endocrine exocrine (ADEX) subtype are robustly KRAS-dependent for survival. The
gene is located on chromosome 12p11-12p12, a region amplified in 5-10% of primary PDACs. Within this amplicon, we identified co-amplification of
with the
gene in a subset of primary human PDACs and PDAC cell lines. Therefore, we determined whether PDAC cell lines are dependent on
expression for proliferation and viability.
encodes a serine/threonine kinase, which shares homology with Hippo pathway kinases LATS1/2. We show that
expression is elevated in a subset of primary PDACs and PDAC cell lines displaying ADEX subtype characteristics, including overexpression of mutant KRAS. RNAi-mediated depletion of STK38L in a subset of ADEX subtype cell lines inhibits cellular proliferation and induces apoptosis. Concomitant with these effects, STK38L depletion causes increased expression of the LATS2 kinase and the cell cycle regulator p21. LATS2 depletion partially rescues the cytostatic and cytotoxic effects of STK38L depletion. Lastly, high
mRNA expression is associated with decreased overall patient survival in PDACs. Collectively, our findings implicate STK38L as a candidate targetable vulnerability in a subset of molecularly-defined PDACs.
The emergence of drug resistance has complicated the management of spinal tuberculosis (TB). While it is well known that the medical management of drug-resistant spinal TB is more difficult, the ...surgical outcomes of the same have not been studied sufficiently, particularly in children.
To analyze the surgical outcomes in a cohort of children treated for spinal TB, and to thus assess whether drug resistant (DR) disease is associated with poorer surgical outcomes.
Retrospective observational study.
All children diagnosed and treated for tuberculous spondylodiscitis at a single center between January 2014 and June 2017.
Surgical outcomes in terms of neurological status and kyphosis angle at final follow-up, and complication rates.
Radiographic and clinical data of children treated for spinal TB with minimum two-year follow-up were retrospectively analyzed. Data gathered included age, gender, level of spine affected, number of vertebrae involved, neurology (Frankel grade), microbiological reports, duration and type of anti-tuberculous therapy (ATT), details of Orthopaedic management and complications during treatment. In DR cases, the time from presentation to starting of second-line ATT was also assessed. Radiographs were reviewed to note the pre- and post-operative degree of kyphosis as well as the angle at final follow-up. Patients that developed major complications were compared statistically with those that did not.
Forty-one consecutive children (mean age 8.5 ± 4.2 years, 20 boys, 21 girls) were treated for spinal TB with a mean follow-up of 31.2 ± 6.4 months. Fifteen were managed conservatively, of which only one had DR-TB. Of the 26 managed surgically, 13 were managed with first-line ATT and 13 required second-line ATT. Of this latter group, eight had microbiologically proven drug resistance, whereas five were switched to second-line therapy presumptively because of failure to show an adequate response to first-line regimen. At last follow-up, all children had completed the prescribed course of ATT and had been declared cured. Neurological improvement was seen in all but one patient; and at last follow-up, 18 children were Frankel E, seven were Frankel D, and one was Frankel B. 11The mean kyphosis angle at presentation was 32.69° ± 21.37°.The immediate post-operative Kyphosis angle averaged 24.38° ± 15.21°. However, six children showed a subsequent worsening of kyphosis, and the Kyphosis angle at last follow-up averaged 30.96° ± 23.92°. Five children had major complications requiring revision surgery; complications included wound dehiscence, vertebral collapse, screw pull-out and implant breakage. Significantly higher number of patients in the group with complications had required second-line ATT (p < .05).
In a cohort of children treated surgically for spinal tuberculosis, a higher complication rate, and thus poor surgical outcomes, were found to be associated with drug resistant disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diagnosis of extrapulmonary tuberculosis (EPTB) poses serious challenges. A careful selection of appropriate gene targets is essential for designing a multiplex-polymerase chain reaction (M-PCR) ...assay.
We compared several gene targets of Mycobacterium tuberculosis, including IS6110, devR, and genes encoding MPB-64 (mpb64), 38kDa (pstS1), 65kDa (hsp65), 30kDa (fbpB), ESAT-6 (esat6), and CFP-10 (cfp10) proteins, using PCR assays on 105 EPTB specimens. From these data, we chose the two best gene targets to design an M-PCR.
Among all gene targets tested, mpb64 showed the highest sensitivity (84% in confirmed cases and 77.5% in clinically suspected cases), followed by IS6110, hsp65, 38kDa, 30kDa, esat6, cfp10, and devR. We used mpb64+IS6110 for designing an M-PCR assay. Our M-PCR assay demonstrated a high sensitivity of 96% in confirmed EPTB cases and 88.75% in clinically suspected EPTB cases with a high specificity of 100%, taking clinical diagnosis as the gold standard.
These M-PCR results along with the clinical findings may facilitate an early diagnosis of EPTB patients and clinical management of disease.
Spinal deformities can either be uniplanar or multiplanar. The current study aims to compare mal-positioned pedicle screw assessment on radiographs versus CT in children <12 years with multiplanar ...and uniplanar spinal deformities.
A cohort of 15 children, mean age 10.1 years, who underwent posterior spinal fusion using free-hand pedicle screw insertion for multiplanar (M) or uniplanar (U) deformities with post-operative radiograph and CT evaluation of 154 screws. The outcome measures included the assessment of malpositions detected on plain radiographs versus CT scans in U and M deformities. The overall breaches in post-operative plain radiographs and CT in each group were compared and analyzed by two independent observers.
The mal-positioned screws were graded on extent of cortical breach on CT. Inter and intra-observer variability was calculated with Kappa(k) method. Sensitivity, Specificity and Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were calculated by comparing breaches on radiographs versus CT considered the gold standard.
In total,154 pedicle screws were analyzed, 65 in U group and 89 in M group. There were 23 (14.9%) malpositioned screws identified on plain radiographs and 43 (27.9%) on CT (p = 0.008). There were 17/154 (11.03%) Grade 1 breaches, 16/154 (10.38%) Grade 2 breaches and 10/154(6.49%) Grade III breaches.
Among the 43 CT breaches, 12/65 (18.46%) were in U group, 31/89 (34.83%) were in M group (p = 0.013).The overall Sensitivity, Specificity and PPV of plain radiographs compared to CT in detecting malpositions were 32.56%, 91.89% and 60.87% respectively.
There was a significant discrepancy in identification of pedicle screw malposition based on plain radiographic versus CT based assessment, more so in multiplanar deformities. The ability to detect a breach on plain radiographs is lesser in multiplanar versus uniplanar deformities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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