Resourcing Defense Innovation: The role of organizational values

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EFFECTS OF TOMMY JOHN SURGERY, DRAFT ORDER, AND MONETARY FACTORS ON THE VALUE OF PITCHERS IN MAJOR LEAGUE BASEBALL

The purpose of this thesis is to determine what effects draft order, monetary earnings, and Tommy John Surgery (TJS) have on the perceived value of a pitcher in Major League Baseball (MLB). For the context of this thesis, value will be defined as a player\u27s ability to contribute to their team\u27s wins in a positive manner. TJS has become synonymous with MLB and baseball as a sport, and many are either skeptical of its effects or over-assuming of its benefits. The three aforementioned areas of concerns were used to structure the thesis, as each dependent outcome is analyzed in a chapter of its own. Multiple articles and studies pertaining to the effects draft order, financial earnings, and TJS may have on pitcher value were compiled and analyzed. Looking at studies between pitchers who underwent TJS prior to being drafted, their order by which they are picked by a team is not as affected as assumed, but the pitcher is more likely to return to the disabled/injured list during their career in MLB. A lens of economic value saw that pitchers who were paid more added to their teams\u27 respective wins. However, the financial loss caused by a pitcher missing time to recover from TJS could outweigh the cost of wins. From a purely Tommy-John standpoint, there are significant changes both beneficial and detrimental to a pitcher\u27s overall statistics. Further research and personal knowledge should be explored prior to receiving TJS as a pitcher. Overall, the factor of TJS seems to have a slightly negative influence on the other two factors and an overall stronger influence than draft order or monetary earnings

Resourcing Defense Innovation: The Role of Organizational Values

Excerpt from the Proceedings of the Nineteenth Annual Acquisition Research SymposiumApproved for public release; distribution is unlimited

A murine model of variant late infantile ceroid lipofuscinosis recapitulates behavioral and pathological phenotypes of human disease.

Neuronal ceroid lipofuscinoses (NCLs; also known collectively as Batten Disease) are a family of autosomal recessive lysosomal storage disorders. Mutations in as many as 13 genes give rise to ∼10 variants of NCL, all with overlapping clinical symptomatology including visual impairment, motor and cognitive dysfunction, seizures, and premature death. Mutations in CLN6 result in both a variant late infantile onset neuronal ceroid lipofuscinosis (vLINCL) as well as an adult-onset form of the disease called Type A Kufs. CLN6 is a non-glycosylated membrane protein of unknown function localized to the endoplasmic reticulum (ER). In this study, we perform a detailed characterization of a naturally occurring Cln6 mutant (Cln6(nclf)) mouse line to validate its utility for translational research. We demonstrate that this Cln6(nclf) mutation leads to deficits in motor coordination, vision, memory, and learning. Pathologically, we demonstrate loss of neurons within specific subregions and lamina of the cortex that correlate to behavioral phenotypes. As in other NCL models, this model displays selective loss of GABAergic interneuron sub-populations in the cortex and the hippocampus with profound, early-onset glial activation. Finally, we demonstrate a novel deficit in memory and learning, including a dramatic reduction in dendritic spine density in the cerebral cortex, which suggests a reduction in synaptic strength following disruption in CLN6. Together, these findings highlight the behavioral and pathological similarities between the Cln6(nclf) mouse model and human NCL patients, validating this model as a reliable format for screening potential therapeutics

Reversible self-assembly of patchy particles into monodisperse icosahedral clusters

We systematically study the design of simple patchy sphere models that reversibly self-assemble into monodisperse icosahedral clusters. We find that the optimal patch width is a compromise between structural specificity (the patches must be narrow enough to energetically select the desired clusters) and kinetic accessibility (they must be sufficiently wide to avoid kinetic traps). Similarly, for good yields the temperature must be low enough for the clusters to be thermodynamically stable, but the clusters must also have enough thermal energy to allow incorrectly formed bonds to be broken. Ordered clusters can form through a number of different dynamic pathways, including direct nucleation and indirect pathways involving large disordered intermediates. The latter pathway is related to a reentrant liquid-to-gas transition that occurs for intermediate patch widths upon lowering the temperature. We also find that the assembly process is robust to inaccurate patch placement up to a certain threshold, and that it is possible to replace the five discrete patches with a single ring patch with no significant loss in yield.Comment: 12 pages, 12 figure

Career decision making in undergraduate medical education

Background: It is unclear how medical students prioritize different factors when selecting a specialty. With rising under and unemployment rates a novel approach to career counselling is becoming increasingly important.  A better understanding of specialty selection could lead to improved career satisfaction amongst graduates while also meeting the health care needs of Canadians.  Methods: Medical students from the University of Toronto participated in a two-phase study looking at factors impacting specialty selection. Phase I consisted of focus groups, conducted independently for each year, and Phase II was a 21-question electronic survey sent to all students.  Results: Twenty-one students participated in the focus group phase and 95 in the survey phase.  Primary themes related to career selection identified in Phase I in order of frequency included personal life factors (36), professional life factors (36), passion/interest (20), changing interests (19) and hidden curriculum (15). The survey phase had similar results with passion (83), lifestyle (79), flexibility (75), employment opportunities (60) and family (50) being ranked as the factors most important in specialty selection. Conclusion: Personal factors, professional factors and passion/interest may be key themes for medical students when deciding which specialty to pursue. Targeting career counselling around these areas may be important.&nbsp

Constraints on the Atmospheric Circulation and Variability of the Eccentric Hot Jupiter XO-3b

We report secondary eclipse photometry of the hot Jupiter XO-3b in the 4.5~$\mu$m band taken with the Infrared Array Camera (IRAC) on the Spitzer Space Telescope. We measure individual eclipse depths and center of eclipse times for a total of twelve secondary eclipses. We fit these data simultaneously with two transits observed in the same band in order to obtain a global best-fit secondary eclipse depth of $0.1580\pm 0.0036\%$ and a center of eclipse phase of $0.67004\pm 0.00013$. We assess the relative magnitude of variations in the dayside brightness of the planet by measuring the size of the residuals during ingress and egress from fitting the combined eclipse light curve with a uniform disk model and place an upper limit of 0.05$\%$. The new secondary eclipse observations extend the total baseline from one and a half years to nearly three years, allowing us to place an upper limit on the periastron precession rate of $2.9\times 10^{-3}$ degrees/day the tightest constraint to date on the periastron precession rate of a hot Jupiter. We use the new transit observations to calculate improved estimates for the system properties, including an updated orbital ephemeris. We also use the large number of secondary eclipses to obtain the most stringent limits to date on the orbit-to-orbit variability of an eccentric hot Jupiter and demonstrate the consistency of multiple-epoch Spitzer observations.Comment: 14 pages, 11 figures, published by Ap

Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies.

NAMPT may represent a novel target for drug discovery in various therapeutic areas, including oncology and inflammation. Additionally, recent work has suggested that targeting NAMPT has potential in treating axon degeneration. In this work, publicly available X-ray co-crystal structures of NAMPT and the structures of two known NAMPT inhibitors were used as the basis for a structure- and ligand-based virtual screening campaign. From this, two novel series of NAMPT inhibitors were identified, one of which showed a statistically significant protective effect when tested in a cellular model of axon degeneration

Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer.

Metastatic non-small cell lung cancer (NSCLC) is a highly fatal and immunogenic malignancy. Although the immune system is known to recognize these tumor cells, one mechanism by which NSCLC can evade the immune system is via overexpression of programmed cell death ligand 1 (PD-L1). Recent clinical trials of PD-1 and PD-L1 inhibitors have returned promising clinical responses. Important for personalizing therapy, patients with higher intensity staining for PD-L1 on tumor biopsies responded better. Thus, there has been interest in using PD-L1 tumor expression as a criterion for patient selection. Currently available methods of screening involve invasive tumor biopsy, followed by histological grading of PD-L1 levels. Biopsies have a high risk of complications, and only allow sampling from limited tumor sections, which may not reflect overall tumor heterogeneity. Circulating tumor cell (CTC) PD-L1 levels could aid in screening patients, and could supplement tissue PD-L1 biopsy results by testing PD-L1 expression from disseminated tumor sites. Towards establishing CTCs as a screening tool, we developed a protocol to isolate CTCs at high purity and immunostain for PD-L1. Monitoring of PD-L1 expression on CTCs could be an additional biomarker for precision medicine that may help in determining response to immunotherapies