Correlational analysis between joint-level kinetics of countermovement jumps and weightlifting derivatives

The purpose of this study was to investigate the mechanical similarity between net joint moments (NJM) of the countermovement jump (CMJ) and the hang power clean (HPC) and jump shrug (JS). Twelve male Lacrosse players performed three maximal effort CMJs and three repetitions of the HPC and JS at 30%, 50%, and 70% of their HPC one repetition maximum (1-RM). Ground reaction forces and motion capture data were used to calculate the NJM of the hip, knee, and ankle joints during each exercise. Statistical comparison of the peak NJM indicated that NJM during the HPC and JS across all loads were equal to or greater than the NJM during the CMJ (all p < 0.025). In addition, correlation analyses indicated that CMJ hip NJM were associated (all p < 0.025) with HPC hip NJM at 30% and 70% (r = 0.611-0.822) and JS hip NJM at 50% and 70% (r = 0.674-0.739), whereas CMJ knee NJM were associated with HPC knee NJM at 70% (r = 0.638) and JS knee NJM at 50% and 70% (r = 0.664-0.732). Further, CMJ ankle NJM were associated with HPC ankle NJM at 30% and 50% (r = 0.615-0.697) and JS ankle NJM at 30%, 50%, and 70% (r = 0.735-0.824). Lastly, knee and ankle NJM during the JS were greater than during the HPC at 30% and 50% of 1-RM (all p < 0.017). The degree of mechanical similarity between the CMJ and the HPC and JS is dependent on the respective load and joint. [Abstract copyright: © Journal of Sports Science and Medicine.

Intracellular Signaling Networks in the Immune Response: Pathways Activated by Interleukin-2 and-4 Receptors and Their Roles in T Cell Proliferation

Cells sense and respond to chemical and physical stimuli through signal transduction pathways, which mediate cell proliferation, differentiation, migration, and survival. The cytokines interleukin-2 (IL-2) and interleukin-4 (IL-4) are key regulators of the adaptive immune system, particularly influencing the clonal expansion and differentiation of T cells. At least in culture, both synergistic and antagonistic effects of IL-2 and -4 co-stimulation have been reported; the antagonism, when observed, is thought to arise from the utilization of a common subunit shared by IL-2 and IL-4 receptors. We have sought to characterize IL-2 and IL-4 signaling at the level of intracellular pathways activated by these receptors. IL-2 receptors are known to activate the Ras/extracellular signal-regulated kinase (Erk) and phosphoinositide (PI) 3-kinase pathways as well as the STAT5 transcription factor. IL-4 is unique among cytokines in that it does not activate Ras/Erk; it does activate PI 3-kinase/Akt as well as a distinct STAT, STAT6. The HT-2 mouse T cell line responds to both IL-2 and -4. We found that IL-4 initially antagonizes, and later synergizes with, IL-2-stimulated HT-2 cell proliferation in a dose-dependent manner. IL-4 also stimulates cell adhesion in static cultures. At the level of intracellular signaling, IL-4 antagonizes IL-2-stimulated activation of Akt, possibly through competition for limiting amounts of common receptor subunit and/or PI 3-kinase. Because IL-4 alone does not promote any Erk activation, we were surprised to find that IL-4 enhances IL-2-stimulated activation of Erk. IL-2/IL-4 co-stimulation provokes transient activation of STAT5 and prolonged activation of STAT6. This extended STAT6 activation may be critical in the IL-2/IL-4 induced synergy in T cell growth. Currently, we are investigating the crosstalk between these pathways and their functional roles in IL-2 and IL-4-stimulated T cell responses

Signaling Pathways Activated by Interleukin-2 and Interluekin-4 Receptors Mediate T Lymphocyte Clonal Expansion

Cells sense and respond to chemical and physical stimuli through signal transduction pathways, which mediate cell proliferation, differentiation, migration, and survival. The cytokines interleukin-2 (IL-2) and interleukin-4 (IL-4) are key regulators of the adaptive immune system, particularly influencing the clonal expansion and differentiation of T cells. At least in culture, both synergistic and antagonistic effects of IL-2 and IL-4 co-stimulation have been reported; the antagonism, when observed, is thought to arise from the utilization of a common subunit shared by IL-2 and IL-4 receptors. We have sought to characterize IL-2 and IL-4 signaling at the level of intracellular pathways activated by these receptors. IL-2 receptors are known to activate the Ras/extracellular signal-regulated kinase (Erk) and phosphoinositide (PI) 3-kinase/Akt pathways as well as the STAT5 transcription factor. IL-4 is unique among cytokines in that it does not activate Ras/Erk; it does activate PI 3-kinase/Akt as well as a distinct STAT, STAT6. The HT-2 mouse T cell line responds to both IL-2 and IL-4. We found that IL-4 initially antagonizes, and later synergizes with, IL-2-stimulated HT-2 cell proliferation in a dose-dependent manner. Additionally, transient signaling through the PI3K/Akt and Ras/Erk pathways are required for optimal T cell proliferation. IL-4 stimulates cell adhesion in static cultures, again in a dose-dependent fashion, and it partially inhibits IL-2-stimulated activation of Akt, Erk and STAT5, consistent with a competition effect. IL-2/IL-4 co-stimulation provokes transient activation of Akt, Erk and STAT5 coupled with prolonged activation of STAT6. This signaling profile and the cell adhesion response suggest potential mechanisms by which IL-4 influences the proliferation of helper T cells

Will The Federal Circuit’s Eli Lilly V. Teva Decision Lead To Efforts To Abuse The Modification Provision Of The Hatch-Waxman Act?

The Hatch-Waxman Act provides a mandatory thirty-month stay on the Food and Drug Administration’s (FDA) approval of an Abbreviated New Drug Application (ANDA) when a patent infringement suit is filed. The Act includes a provision for a district court to shorten or extend the Act’s thirty-month stay on FDA approval if “either party to the action failed to reasonably cooperate in expediting the action

Interorganizational Information Exchange and Efficiency: Organizational Performance in Emergency Environments

Achieving efficiency in coordinated action in rapidly changing environments has challenged both researchers and practitioners. Emergency events require both rapid response and effective coordination among participating organizations. We created a simulated operations environment using agent-based modeling to test the efficiency of six different organizational designs that varied the exercise of authority, degree of uncertainty, and access to information. Efficiency is measured in terms of response time, identifying time as the most valuable resource in emergency response. Our findings show that, contrary to dominant organizational patterns of hierarchical authority that limit communication among members via strict reporting rules, any communication among members increases the efficiency of organizations operating in uncertain environments. We further found that a smaller component of highly interconnected, self adapting agents emerges over time to support the organization\'s adaptation in changing conditions. In uncertain environments, heterogeneous agents prove more efficient in sharing information that guides coordination than homogeneous agents.Agent-Based Simulation, Emergency Management, Network Evolution, Performance

Topological partition relations to the form omega^*-> (Y)^1_2

Theorem: The topological partition relation omega^{*}-> (Y)^{1}_{2} (a) fails for every space Y with |Y| >= 2^c ; (b) holds for Y discrete if and only if |Y| <= c; (c) holds for certain non-discrete P-spaces Y ; (d) fails for Y= omega cup {p} with p in omega^{*} ; (e) fails for Y infinite and countably compact

Department of Homeland Security Science and Technology Directorate: Developing Technology to Protect America

In response to a congressional mandate and in consultation with Department of Homeland Security's (DHS) Science and Technology Directorate (S&T), the National Academy conducted a review of S&T's effectiveness and efficiency in addressing homeland security needs. This review included a particular focus that identified any unnecessary duplication of effort, and opportunity costs arising from an emphasis on homeland security-related research. Under the direction of the National Academy Panel, the study team reviewed a wide variety of documents related to S&T and homeland security-related research in general. The team also conducted interviews with more than 200 individuals, including S&T officials and staff, officials from other DHS component agencies, other federal agencies engaged in homeland security-related research, and experts from outside government in science policy, homeland security-related research and other scientific fields.Key FindingsThe results of this effort indicated that S&T faces a significant challenge in marshaling the resources of multiple federal agencies to work together to develop a homeland security-related strategic plan for all agencies. Yet the importance of this role should not be underestimated. The very process of working across agencies to develop and align the federal homeland security research enterprise around a forward-focused plan is critical to ensuring that future efforts support a common vision and goals, and that the metrics by which to measure national progress, and make changes as needed, are in place

Slow Release of Ions from Internalized Silver Nanoparticles Modifies the Epidermal Growth Factor Signaling Response

Due to their distinctive physiochemical properties, including a robust antibacterial activity and plasmonic capability, hundreds of consumer and medical products contain colloidal silver nanoparticles (AgNPs). However, even at sub-toxic dosages, AgNPs are able to disrupt cell functionality, through a yet unknown mechanism. Moreover, internalized AgNPs have the potential to prolong this disruption, even after the removal of excess particles. In the present study, we evaluated the impact, mechanism of action, and continual effects of 50 nm AgNP exposure on epidermal growth factor (EGF) signal transduction within a human keratinocyte (HaCaT) cell line. After AgNP expose, EGF signaling was initially obstructed due to the dissolution of particles into silver ions. However, at longer durations, the internalized AgNPs increased EGF signaling activity. This latter behavior correlated to sustained HaCaT stress, believed to be maintained through the continual dissolution of internalized AgNPs. This study raises concerns that even after exposure ceases, the retained nanomaterials are capable of acting as a slow-release mechanism for metallic ions; continually stressing and modifying normal cellular functionality

Less Is More: Long-Term in Vitro Exposure to Low Levels of Silver Nanoparticles Provides New Insights for Nanomaterial Evaluation

In view of the vast number of new nanomaterials (NMs) that require testing and the constraints associated with animal models, the majority of studies to elucidate nanotoxicological effects have occurred in vitro, with limited correlation and applicability to in vivo systems and realistic, occupational exposure scenarios. In this study, we developed and implemented a chronic in vitromodel coupled with lower, regulatory dosages in order to provide a more realistic assessment of NM-dependent consequences and illuminate the implications of long-term NM exposure. When keratinocytes were exposed to 50 nm silver nanoparticles (Ag-NPs), we determined that chronically dosed cells operated under augmented stress and modified functionality in comparison to their acute counterparts. Specifically, Ag-NP exposure through a chronic mechanism increased p38 activation, actin disorganization, heightened ki67 expression, and extensive gene modification. Additionally, chronic Ag-NP exposure altered the way in which cells perceived and responded to epidermal growth factor stimulation, indicating a transformation of cell functionality. Most importantly, this study demonstrated that chronic exposure in the pg/mL range to Ag-NPs did not induce a cytotoxic response, but instead activated sustained stress and signaling responses, suggesting that cells are able to cope with prolonged, low levels of Ag-NP exposure. In summary, we demonstrated that through implementation of a chronic dosimetry paradigm, which more closely resembles realistic NM exposure scenarios, it is possible to illuminate long-term cellular consequences, which greatly differ from previously obtained acute assessments