Aerial capsule emergency separation device Patent

Aerial capsule emergency separation device using jettisonable tower

RANKL Signaling Sustains Primary Tumor Growth in Genetically Engineered Mouse Models of Lung Adenocarcinoma.

NSCLC is the leading cause of cancer mortality. Recent retrospective clinical analyses suggest that blocking the receptor activator of NF-κB (RANK) signaling pathway inhibits the growth of NSCLC and might represent a new treatment strategy. Receptor activator of NF-κB gene (RANK) and receptor activator of NF-κB ligand gene (RANKL) expression in human lung adenocarcinoma was interrogated from publicly available gene expression data sets. Several genetically engineered mouse models were used to evaluate treatment efficacy of RANK-Fc to block RANKL, with primary tumor growth measured longitudinally using microcomputed tomography. A combination of RANKL blockade with cisplatin was tested to mirror an ongoing clinical trial. In human lung adenocarcinoma data sets, RANKL expression was associated with decreased survival and KRAS mutation, with the highest levels in tumors with co-occurring KRAS and liver kinase B1 gene (LKB1) mutations. In Kras <sup>LSL-G12D/WT</sup> , Kras <sup>LSL-G12D/WT</sup> ; Lkb1 <sup>Flox/Flox</sup> and Kras <sup>LSL-G12D/WT</sup> ; p53 <sup>Flox/Flox</sup> mouse models of lung adenocarcinoma, we monitored an impaired progression of tumors upon RANKL blockade. Despite elevated expression of RANKL and RANK in immune cells, treatment response was not associated with major changes in the tumor immune microenvironment. Combined RANK-Fc with cisplatin revealed increased efficacy compared with that of single agents in p53- but not in Lkb1-deficient tumors. RANKL blocking agents impair the growth of primary lung tumors in several mouse models of lung adenocarcinoma and suggest that patients with KRAS-mutant lung tumors will benefit from such treatments

Space capsule Patent

Manned space capsule configuration for orbital flight and atmospheric reentr

The holistic rhizosphere: integrating zones, processes, and semantics in the soil influenced by roots

Despite often being conceptualized as a thin layer of soil around roots, the rhizosphere is actually a dynamic system of interacting processes. Hiltner originally defined the rhizosphere as the soil influenced by plant roots. However, soil physicists, chemists, microbiologists, and plant physiologists have studied the rhizosphere independently, and therefore conceptualized the rhizosphere in different ways and using contrasting terminology. Rather than research-specific conceptions of the rhizosphere, the authors propose a holistic rhizosphere encapsulating the following components: microbial community gradients, macroorganisms, mucigel, volumes of soil structure modification, and depletion or accumulation zones of nutrients, water, root exudates, volatiles, and gases. These rhizosphere components are the result of dynamic processes and understanding the integration of these processes will be necessary for future contributions to rhizosphere science based upon interdisciplinary collaborations. In this review, current knowledge of the rhizosphere is synthesized using this holistic perspective with a focus on integrating traditionally separated rhizosphere studies. The temporal dynamics of rhizosphere activities will also be considered, from annual fine root turnover to diurnal fluctuations of water and nutrient uptake. The latest empirical and computational methods are discussed in the context of rhizosphere integration. Clarification of rhizosphere semantics, a holistic model of the rhizosphere, examples of integration of rhizosphere studies across disciplines, and review of the latest rhizosphere methods will empower rhizosphere scientists from different disciplines to engage in the interdisciplinary collaborations needed to break new ground in truly understanding the rhizosphere and to apply this knowledge for practical guidance

Victim-offender mediation and social work: focus groups with mediators in Flanders

The role of social work in the restorative justice field remains largely unexplored. This article reports on the findings of focus groups conducted with mediators of juvenile and adult mediation practices in Flanders (Belgium) to gain more insight into how mediators perceive their professional role and to what extent they refer to individual and structural dimensions of social work practice. Implications for future social work involvement and research are made

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

Psychiatric and psychological follow-up of undergraduate and postgraduate medical students: prevalence and associated factors. Results from the national BOURBON study. Running title: mental health and addictive behavior of medical students

International audienceBackground. Physicians are at risk of burnout, anxiety and depression. Prevention i

Autocrine Adenosine Regulates Tumor Polyfunctional CD73⁺CD4⁺ Effector T Cells Devoid of Immune Checkpoints.

The production of CD73-derived adenosine (Ado) by Tregs has been proposed as a resistance mechanism to anti-PD-1 therapy in murine tumor models. We reported that human Tregs express the ectonucleotidase CD39, which generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effector CD4 <sup>+</sup> T cells (Teffs) enriched in polyfunctional Th1.17 cells characterized by expression of CXCR3, CCR6, and MDR1, and production of IL17A/IFNγ/IL22/GM-CSF. CD39 <sup>+</sup> Tregs selectively targeted CD73 <sup>+</sup> Teffs through cooperative degradation of ATP into Ado inhibiting and restricting the ability of CD73 <sup>+</sup> Teffs to secrete IL17A. CD73 <sup>+</sup> Teffs infiltrating breast and ovarian tumors were functionally blunted by Tregs expressing upregulated levels of CD39 and ATPase activity. Moreover, tumor-infiltrating CD73 <sup>+</sup> Teffs failed to express inhibitory immune checkpoints, suggesting that CD73 might be selected under pressure from immune checkpoint blockade therapy and thus may represent a nonredundant target for restoring antitumor immunity.Significance: Polyfunctional CD73 <sup>+</sup> T-cell effectors lacking other immune checkpoints are selectively targeted by CD39 overexpressing Tregs that dominate the breast tumor environment. Cancer Res; 78(13); 3604-18. ©2018 AACR

Termination of the leprosy isolation policy in the US and Japan : Science, policy changes, and the garbage can model

BACKGROUND: In both the US and Japan, the patient isolation policy for leprosy /Hansen's disease (HD) was preserved along with the isolation facilities, long after it had been proven to be scientifically unnecessary. This delayed policy termination caused a deprivation of civil liberties of the involuntarily confined patients, the fostering of social stigmas attached to the disease, and an inefficient use of health resources. This article seeks to elucidate the political process which hindered timely policy changes congruent with scientific advances. METHODS: Examination of historical materials, supplemented by personal interviews. The role that science played in the process of policy making was scrutinized with particular reference to the Garbage Can model. RESULTS: From the vantage of history, science remained instrumental in all period in the sense that it was not the primary objective for which policy change was discussed or intended, nor was it the principal driving force for policy change. When the argument arose, scientific arguments were employed to justify the patient isolation policy. However, in the early post-WWII period, issues were foregrounded and agendas were set as the inadvertent result of administrative reforms. Subsequently, scientific developments were more or less ignored due to concern about adverse policy outcomes. Finally, in the 1980s and 1990s, scientific arguments were used instrumentally to argue against isolation and for the termination of residential care. CONCLUSION: Contrary to public expectations, health policy is not always rational and scientifically justified. In the process of policy making, the role of science can be limited and instrumental. Policy change may require the opening of policy windows, as a result of convergence of the problem, policy, and political streams, by effective exercise of leadership. Scientists and policymakers should be attentive enough to the political context of policies