An Alternative to Compactification

Conventional wisdom states that Newton's force law implies only four non-compact dimensions. We demonstrate that this is not necessarily true in the presence of a non-factorizable background geometry. The specific example we study is a single 3-brane embedded in five dimensions. We show that even without a gap in the Kaluza-Klein spectrum, four-dimensional Newtonian and general relativistic gravity is reproduced to more than adequate precision.Comment: LaTex, 9 page

Care Coordination Guidelines for the Care of People with Spina Bifida

Care coordination is the deliberate organization of patient care activities between two or more participants (including the patient) involved in a person’s care to facilitate the appropriate delivery of health care services. Organizing care involves the marshalling of personnel and other resources needed to carry out all required patient care activities. It is often managed by the exchange of information among participants responsible for different aspects of care. With an estimated 85% of individuals with Spina Bifida (SB) surviving to adulthood, SB specific care coordination guidelines are warranted. Care coordination (also described as case management services) is a process that links them to services and resources in a coordinated effort to maximize their potential by providing optimal health care. However, care can be complicated due to the medical complexities of the condition and the need for multidisciplinary care, as well as economic and sociocultural barriers. It is often a shared responsibility by the multidisciplinary Spina Bifida team. For this reason, the Spina Bifida Care Coordinator has the primary responsibility for overseeing the overall treatment plan for the individual with Spina Bifida. Care coordination includes communication with the primary care provider in a patient’s medical home. This article discusses the Spina Bifida Care Coordination Guideline from the 2018 Spina Bifida Association’s Fourth Edition of the Guidelines for the Care of People with Spina Bifida and explores care coordination goals for different age groups as well as further research topics in SB care coordination

Are interactions between epicardial adipose tissue, cardiac fibroblasts and cardiac myocytes instrumental in atrial fibrosis and atrial fibrillation?

Atrial fibrillation is very common among the elderly and/or obese. While myocardial fibrosis is associated with atrial fibrillation, the exact mechanisms within atrial myocytes and surrounding non-myocytes are not fully understood. This review considers the potential roles of myocardial fibroblasts and myofibroblasts in fibrosis and modulating myocyte electrophysiology through electrotonic interactions. Coupling with (myo)fibroblasts in vitro and in silico prolonged myocyte action potential duration and caused resting depolarization; an optogenetic study has verified in vivo that fibroblasts depolarized when coupled myocytes produced action potentials. This review also introduces another non-myocyte which may modulate both myocardial (myo)fibroblasts and myocytes: epicardial adipose tissue. Epicardial adipocytes are in intimate contact with myocytes and (myo)fibroblasts and may infiltrate the myocardium. Adipocytes secrete numerous adipokines which modulate (myo)fibroblast and myocyte physiology. These adipokines are protective in healthy hearts, preventing inflammation and fibrosis. However, adipokines secreted from adipocytes may switch to pro-inflammatory and pro-fibrotic, associated with reactive oxygen species generation. Pro-fibrotic adipokines stimulate myofibroblast differentiation, causing pronounced fibrosis in the epicardial adipose tissue and the myocardium. Adipose tissue also influences myocyte electrophysiology, via the adipokines and/or through electrotonic interactions. Deeper understanding of the interactions between myocytes and non-myocytes is important to understand and manage atrial fibrillation

Oxygen, Ecology, and the Cambrian Radiation of Animals

The Proterozoic-Cambrian transition records the appearance of essentially all animal body plans (phyla), yet to date no single hypothesis adequately explains both the timing of the event and the evident increase in diversity and disparity. Ecological triggers focused on escalatory predator–prey “arms races” can explain the evolutionary pattern but not its timing, whereas environmental triggers, particularly ocean/atmosphere oxygenation, do the reverse. Using modern oxygen minimum zones as an analog for Proterozoic oceans, we explore the effect of low oxygen levels on the feeding ecology of polychaetes, the dominant macrofaunal animals in deep-sea sediments. Here we show that low oxygen is clearly linked to low proportions of carnivores in a community and low diversity of carnivorous taxa, whereas higher oxygen levels support more complex food webs. The recognition of a physiological control on carnivory therefore links environmental triggers and ecological drivers, providing an integrated explanation for both the pattern and timing of Cambrian animal radiation.Earth and Planetary SciencesOrganismic and Evolutionary Biolog

A Large Mass Hierarchy from a Small Extra Dimension

We propose a new higher-dimensional mechanism for solving the Hierarchy Problem. The Weak scale is generated from a large scale of order the Planck scale through an exponential hierarchy. However, this exponential arises not from gauge interactions but from the background metric (which is a slice of AdS_5 spacetime). This mechanism relies on the existence of only a single additional dimension. We demonstrate a simple explicit example of this mechanism with two three-branes, one of which contains the Standard Model fields. The experimental consequences of this scenario are new and dramatic. There are fundamental spin-2 excitations with mass of weak scale order, which are coupled with weak scale as opposed to gravitational strength to the standard model particles. The phenomenology of these models is quite distinct from that of large extra dimension scenarios; none of the current constraints on theories with very large extra dimensions apply.Comment: 9 pages, LaTe

Development of a fluorescence-based method for monitoring glucose catabolism and its potential use in a biomass hydrolysis assay

<p>Abstract</p> <p>Background</p> <p>The availability and low cost of lignocellulosic biomass has caused tremendous interest in the bioconversion of this feedstock into liquid fuels. One measure of the economic viability of the bioconversion process is the ease with which a particular feedstock is hydrolyzed and fermented. Because monitoring the analytes in hydrolysis and fermentation experiments is time consuming, the objective of this study was to develop a rapid fluorescence-based method to monitor sugar production during biomass hydrolysis, and to demonstrate its application in monitoring corn stover hydrolysis.</p> <p>Results</p> <p>Hydrolytic enzymes were used in conjunction with <it>Escherichia coli </it>strain CA8404 (a hexose and pentose-consuming strain), modified to produce green fluorescent protein (GFP). The combination of hydrolytic enzymes and a sugar-consuming organism minimizes feedback inhibition of the hydrolytic enzymes. We observed that culture growth rate as measured by change in culture turbidity is proportional to GFP fluorescence and total growth and growth rate depends upon how much sugar is present at inoculation. Furthermore, it was possible to monitor the course of enzymatic hydrolysis in near real-time, though there are instrumentation challenges in doing this.</p> <p>Conclusion</p> <p>We found that instantaneous fluorescence is proportional to the bacterial growth rate. As growth rate is limited by the availability of sugar, the integral of fluorescence is proportional to the amount of sugar consumed by the microbe. We demonstrate that corn stover varieties can be differentiated based on sugar yields in enzymatic hydrolysis reactions using post-hydrolysis fluorescence measurements. Also, it may be possible to monitor fluorescence in real-time during hydrolysis to compare different hydrolysis protocols.</p

Intracellular \u3cem\u3eSalmonella\u3c/em\u3e delivery of an exogenous immunization antigen refocuses CD8 T cells against cancer cells, eliminates pancreatic tumors and forms antitumor immunity

Introduction: Immunotherapies have shown great promise, but are not effective for all tumors types and are effective in less than 3% of patients with pancreatic ductal adenocarcinomas (PDAC). To make an immune treatment that is effective for more cancer patients and those with PDAC specifically, we genetically engineered Salmonella to deliver exogenous antigens directly into the cytoplasm of tumor cells. We hypothesized that intracellular delivery of an exogenous immunization antigen would activate antigen-specific CD8 T cells and reduce tumors in immunized mice. Methods: To test this hypothesis, we administered intracellular delivering (ID) Salmonella that deliver ovalbumin as a model antigen into tumor-bearing, ovalbumin-vaccinated mice. ID Salmonella delivers antigens by autonomously lysing in cells after the induction of cell invasion. Results: We showed that the delivered ovalbumin disperses throughout the cytoplasm of cells in culture and in tumors. This delivery into the cytoplasm is essential for antigen cross-presentation. We showed that co-culture of ovalbumin-recipient cancer cells with ovalbumin-specific CD8 T cells triggered a cytotoxic T cell response. After the adoptive transfer of OT-I CD8 T cells, intracellular delivery of ovalbumin reduced tumor growth and eliminated tumors. This effect was dependent on the presence of the ovalbumin-specific T cells. Following vaccination with the exogenous antigen in mice, intracellular delivery of the antigen cleared 43% of established KPC pancreatic tumors, increased survival, and prevented tumor re-implantation. Discussion: This response in the immunosuppressive KPC model demonstrates the potential to treat tumors that do not respond to checkpoint inhibitors, and the response to re-challenge indicates that new immunity was established against intrinsic tumor antigens. In the clinic, ID Salmonella could be used to deliver a protein antigen from a childhood immunization to refocus pre-existing T cell immunity against tumors. As an off-the-shelf immunotherapy, this bacterial system has the potential to be effective in a broad range of cancer patients

Pharmacy patron perspectives of community pharmacist administered influenza vaccinations

The final publication is available at Elsevier via https://doi.org/10.1016/j.sapharm.2018.04.015. © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/One approach to boost influenza vaccination coverage has been to expand immunization authority. In 2012, the province of Ontario gave community pharmacists the authority to administer the influenza vaccine.This study was conducted as part of the Ontario Pharmacy Evidence Network (OPEN) and funded by the Government of Ontario

Out Of This World Supersymmetry Breaking

We show that in a general hidden sector model, supersymmetry breaking necessarily generates at one-loop a scalar and gaugino mass as a consequence of the super-Weyl anomaly. We study a scenario in which this contribution dominates. We consider the Standard Model particles to be localized on a (3+1)-dimensional subspace or ``3-brane'' of a higher dimensional spacetime, while supersymmetry breaking occurs off the 3-brane, either in the bulk or on another 3-brane. At least one extra dimension is assumed to be compactified roughly one to two orders of magnitude below the four-dimensional Planck scale. This framework is phenomenologically very attractive; it introduces new possibilities for solving the supersymmetric flavor problem, the gaugino mass problem, the supersymmetric CP problem, and the mu-problem. Furthermore, the compactification scale can be consistent with a unification of gauge and gravitational couplings. We demonstrate these claims in a four-dimensional effective theory below the compactification scale that incorporates the relevant features of the underlying higher dimensional theory and the contribution of the super-Weyl anomaly. Naturalness constraints follow not only from symmetries but also from the higher dimensional origins of the theory. We also introduce additional bulk contributions to the MSSM soft masses. This scenario is very predictive: the gaugino masses, squark masses, and $A$ terms are given in terms of MSSM renormalization group functions.Comment: 42 pages, LateX, references added, corrections added as Eqs. (43, 53