Vision and Objectives

The purpose of Industry Day is to exchange information with industry to increase understanding of the Government's current vision and objectives for the xEVA Production and Services Contract. The presentation provides industry with the opportunity to provide input into the xEVAPS procurement strategy and encourage offerors to submit questions and comments. A technical overview of the xEVA System serves as the foundation for the content related to draft requirements in the SOW

Minimizing Bias in Biomass Allometry: Model Selection and Log‐Transformation of Data

Nonlinear regression is increasingly used to develop allometric equations for forest biomass estimation (i.e., as opposed to the traditional approach of log‐transformation followed by linear regression). Most statistical software packages, however, assume additive errors by default, violating a key assumption of allometric theory and possibly producing spurious models. Here, we show that such models may bias stand‐level biomass estimates by up to 100 percent in young forests, and we present an alternative nonlinear fitting approach that conforms with allometric theory

Comparing Fixed-amount and Progressive-amount DRO Schedules for Tic Suppression in Youth with Chronic Tic Disorders

Chronic tic disorders (CTDs) involve motor and/or vocal tics that often cause substantial distress and impairment. Differential reinforcement of other behavior (DRO) schedules of reinforcement produce robust, but incomplete, reductions in tic frequency in youth with CTDs; however, a more robust reduction may be needed to affect durable clinical change. Standard, fixed‐amount DRO schedules have not commonly yielded such reductions, so we evaluated a novel, progressive‐amount DRO schedule, based on its ability to facilitate sustained abstinence from functionally similar behaviors. Five youth with CTDs were exposed to periods of baseline, fixed‐amount DRO (DRO‐F), and progressive‐amount DRO (DRO‐P). Both DRO schedules produced decreases in tic rate and increases in intertic interval duration, but no systematic differences were seen between the two schedules on any dimension of tic occurrence. The DRO‐F schedule was generally preferred to the DRO‐P schedule. Possible procedural improvements and other future directions are discussed

Computerized Response Inhibition Training For Children With Trichotillomania

Evidence suggests that trichotillomania is characterized by impairment in response inhibition, which is the ability to suppress pre-potent/dominant but inappropriate responses. This study sought to test the feasibility of computerized response inhibition training for children with trichotillomania. Twenty-two children were randomized to the 8-session response inhibition training (RIT; n = 12) or a waitlisted control (WLT; n = 10). Primary outcomes were assessed by an independent evaluator, using the Clinical Global Impression-Improvement (CGI-I), and the NIMH Trichotillomania Severity (NIMH-TSS) and Impairment scales (NIMH-TIS) at pre, post-training/waiting, and 1-month follow-up. Relative to the WLT group, the RIT group showed a higher response rate (55% vs. 11%) on the CGI-I and a lower level of impairment on the NIMH-TIS, at post-training. Overall symptom reductions rates on the NIMH-TSS were 34% (RIT) vs. 21% (WLT) at post-training. The RIT\u27s therapeutic gains were maintained at 1-month follow-up, as indicated by the CGI-I responder status (= 66%), and a continuing reduction in symptom on the NIMH-TSS. This pattern of findings was also replicated by the 6 waitlisted children who received the same RIT intervention after post-waiting assessment. Results suggest that computerized RIT may be a potentially useful intervention for trichotillomania

Allosteric p97 inhibitors can overcome resistance to ATP-competitive p97 inhibitors for potential anti-cancer therapy

A major challenge of targeted cancer therapy is the selection for drug‐resistant mutations in tumor cells leading to loss of treatment effectiveness. p97/VCP is a central regulator of protein homeostasis and a promising anti‐cancer target because of its vital role in cell growth and survival. One ATP‐competitive p97 inhibitor, CB‐5083, has entered clinical trials. Selective pressure on HCT116 cells treated with CB‐5083 identified 5 different resistant mutants. Identification of p97 inhibitors with different mechanisms of action would offer the potential to overcome this class of resistance mutations. Our results demonstrate that two CB‐5083 resistant p97 mutants, N660K and T688A, were also resistant to several other ATP‐competitive p97 inhibitors, whereas inhibition by two allosteric p97 inhibitors NMS‐873 and UPCDC‐30245 were unaffected by these mutations. We also established a CB‐5083 resistant cell line that harbors a new p97 double mutation (D649A/T688A). While CB‐5083, NMS‐873, and UPCDC‐30245 all effectively inhibited proliferation of the parental HCT116 cell line, NMS‐873 and UPCDC‐30245 were 30‐fold more potent than CB‐5083 in inhibiting the CB‐5083 resistant D649A/T688A double mutant. Our results suggest that allosteric p97 inhibitors are promising alternatives when resistance to ATP‐competitive p97 inhibitors arises during anti‐cancer treatment