A Scenario-based Parametric Analysis of the Army Personnel-to-assignment Matching Problem

This study aims to compare linear programming and stable marriage approaches to the personnel assignment problem under conditions of uncertainty. Robust solutions should exhibit reduced variability of solutions in the presence of one or more additional constraints or problem perturbations added to some baseline problems.Several variations of each approach are compared with respect to solution speed, solution quality as measured by officer-to-assignment preferences and solution robustness as measured by the number of assignment changes required after inducing a set of representative perturbations or constraints to an assignment instance. These side constraints represent the realistic assignment categorical priorities and limitations encountered by army assignment managers who solve this problem semiannually, and thus the synthetic instances considered herein emulate typical problem instances

Exploiting Connections for Viral Replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 (coronavirus disease 2019) pandemic, is a positive strand RNA (+RNA) virus. Like other +RNA viruses, SARS-CoV-2 is dependent on host cell metabolic machinery to survive and replicate, remodeling cellular membranes to generate sites of viral replication. Viral RNA-containing double-membrane vesicles (DMVs) are a striking feature of +RNA viral replication and are abundant in SARS-CoV-2-infected cells. Their generation involves rewiring of host lipid metabolism, including lipid biosynthetic pathways. Viruses can also redirect lipids from host cell organelles; lipid exchange at membrane contact sites, where the membranes of adjacent organelles are in close apposition, has been implicated in the replication of several +RNA viruses. Here we review current understanding of DMV biogenesis. With a focus on the exploitation of contact site machinery by +RNA viruses to generate replication organelles, we discuss evidence that similar mechanisms support SARS-CoV-2 replication, protecting its RNA from the host cell immune response

Exploiting Connections for Viral Replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 (coronavirus disease 2019) pandemic, is a positive strand RNA (+RNA) virus. Like other +RNA viruses, SARS-CoV-2 is dependent on host cell metabolic machinery to survive and replicate, remodeling cellular membranes to generate sites of viral replication. Viral RNA-containing double-membrane vesicles (DMVs) are a striking feature of +RNA viral replication and are abundant in SARS-CoV-2-infected cells. Their generation involves rewiring of host lipid metabolism, including lipid biosynthetic pathways. Viruses can also redirect lipids from host cell organelles; lipid exchange at membrane contact sites, where the membranes of adjacent organelles are in close apposition, has been implicated in the replication of several +RNA viruses. Here we review current understanding of DMV biogenesis. With a focus on the exploitation of contact site machinery by +RNA viruses to generate replication organelles, we discuss evidence that similar mechanisms support SARS-CoV-2 replication, protecting its RNA from the host cell immune response

Analysis of margin classification systems for assessing the risk of local recurrence after soft tissue sarcoma resection

Purpose: To compare the ability of margin classification systems to determine local recurrence (LR) risk after soft tissue sarcoma (STS) resection. Methods: Two thousand two hundred seventeen patients with nonmetastatic extremity and truncal STS treated with surgical resection and multidisciplinary consideration of perioperative radiotherapy were retrospectively reviewed. Margins were coded by residual tumor (R) classification (in which microscopic tumor at inked margin defines R1), the R+1mm classification (in which microscopic tumor within 1 mm of ink defines R1), and the Toronto Margin Context Classification (TMCC; in which positive margins are separated into planned close but positive at critical structures, positive after whoops re-excision, and inadvertent positive margins). Multivariate competing risk regression models were created. Results: By R classification, LR rates at 10-year follow-up were 8%, 21%, and 44% in R0, R1, and R2, respectively. R+1mm classification resulted in increased R1 margins (726 v 278, P < .001), but led to decreased LR for R1 margins without changing R0 LR; for R0, the 10-year LR rate was 8% (range, 7% to 10%); for R1, the 10-year LR rate was 12% (10% to 15%) . The TMCC also showed various LR rates among its tiers (P < .001). LR rates for positive margins on critical structures were not different from R0 at 10 years (11% v 8%, P = .18), whereas inadvertent positive margins had high LR (5-year, 28% [95% CI, 19% to 37%]; 10-year, 35% [95% CI, 25% to 46%]; P < .001). Conclusion: The R classification identified three distinct risk levels for LR in STS. An R+1mm classification reduced LR differences between R1 and R0, suggesting that a negative but < 1-mm margin may be adequate with multidisciplinary treatment. The TMCC provides additional stratification of positive margins that may aid in surgical planning and patient education

Is Biventricular Vascular Coupling a Better Indicator of Ventriculo-Ventricular Interaction in Congenital Heart Disease?

BACKGROUND: Ventriculo-ventricular interactions are known to exist, though not well quantified. We hypothesised that the ventricular-vascular coupling ratio assessed by cardiovascular MRI would provide insight into this relationship. We also sought to compare MRI-derived ventricular-vascular coupling ratio to echocardiography and patient outcomes. METHODS: Children with cardiac disease and biventricular physiology were included. Sanz\u27s and Bullet methods were used to calculate ventricular-vascular coupling ratio by MRI and echocardiography, respectively. Subgroup analysis was performed for right and left heart diseases. Univariate and multivariate regressions were performed to determine associations with outcomes. RESULTS: A total of 55 patients (age 14.3 ± 2.5 years) were included. Biventricular ventricular-vascular coupling ratio by MRI correlated with each other (r = 0.41; p = 0.003), with respect to ventricle\u27s ejection fraction (r = -0.76 to -0.88; p \u3c 0.001) and other ventricle\u27s ejection fraction (r = -0.42 to -0.47; p \u3c 0.01). However, biventricular ejection fraction had only weak correlation with each other (r = 0.31; p = 0.02). Echo underestimated ventricular-vascular coupling ratio for the left ventricle (p \u3c 0.001) with modest correlation to MRI-derived ventricular-vascular coupling ratio (r = 0.43; p = 0.002). There seems to be a weak correlation between uncoupled right ventricular-vascular coupling ratio with the need for intervention and performance on exercise testing (r = 0.33; p = 0.02). CONCLUSION: MRI-derived biventricular ventricular-vascular coupling ratio provides a better estimate of ventriculo-ventricular interaction in children and adolescents with CHD. These associations are stronger than traditional parameters and applicable to right and left heart conditions

A Functional Role for ADAM10 in Human Immunodeficiency Virus Type-1 Replication

<p>Abstract</p> <p>Background</p> <p>Gene trap insertional mutagenesis was used as a high-throughput approach to discover cellular genes participating in viral infection by screening libraries of cells selected for survival from lytic infection with a variety of viruses. Cells harboring a disrupted <it>ADAM10 </it>(A Disintegrin and Metalloprotease 10) allele survived reovirus infection, and subsequently ADAM10 was shown by RNA interference to be important for replication of HIV-1.</p> <p>Results</p> <p>Silencing ADAM10 expression with small interfering RNA (siRNA) 48 hours before infection significantly inhibited HIV-1 replication in primary human monocyte-derived macrophages and in CD4⁺cell lines. In agreement, ADAM10 over-expression significantly increased HIV-1 replication. ADAM10 down-regulation did not inhibit viral reverse transcription, indicating that viral entry and uncoating are also independent of ADAM10 expression. Integration of HIV-1 cDNA was reduced in ADAM10 down-regulated cells; however, concomitant 2-LTR circle formation was not detected, suggesting that HIV-1 does not enter the nucleus. Further, ADAM10 silencing inhibited downstream reporter gene expression and viral protein translation. Interestingly, we found that while the metalloprotease domain of ADAM10 is not required for HIV-1 replication, ADAM15 and γ-secretase (which proteolytically release the extracellular and intracellular domains of ADAM10 from the plasma membrane, respectively) do support productive infection.</p> <p>Conclusions</p> <p>We propose that ADAM10 facilitates replication at the level of nuclear trafficking. Collectively, our data support a model whereby ADAM10 is cleaved by ADAM15 and γ-secretase and that the ADAM10 intracellular domain directly facilitates HIV-1 nuclear trafficking. Thus, ADAM10 represents a novel cellular target class for development of antiretroviral drugs.</p