236 research outputs found
Warped Higgsless Models with IR--Brane Kinetic Terms
We examine a warped Higgsless model
in 5-- with IR(TeV)--brane kinetic terms. It is shown that adding a brane
term for the gauge field does not affect the scale (
TeV) where perturbative unitarity in is violated.
This term could, however, enhance the agreement of the model with the precision
electroweak data. In contrast, the inclusion of a kinetic term corresponding to
the custodial symmetry of the theory delays the unitarity violation
in scattering to energy scales of TeV for a significant
fraction of the parameter space. This is about a factor of 4 improvement
compared to the corresponding scale of unitarity violation in the Standard
Model without a Higgs. We also show that null searches for extra gauge bosons
at the Tevatron and for contact interactions at LEP II place non-trivial bounds
on the size of the IR-brane terms.Comment: 23 pages, 8 figure
Monte Carlo Exploration of Warped Higgsless Models
We have performed a detailed Monte Carlo exploration of the parameter space
for a warped Higgsless model of electroweak symmetry breaking in 5 dimensions.
This model is based on the gauge group
in an AdS bulk with arbitrary gauge kinetic terms on both the Planck and
TeV branes. Constraints arising from precision electroweak measurements and
collider data are found to be relatively easy to satisfy. We show, however,
that the additional requirement of perturbative unitarity up to the cut-off,
TeV, in elastic scattering in the absence of dangerous
tachyons eliminates all models. If successful models of this class exist, they
must be highly fine-tuned.Comment: 26 pages, 7 figures; new fig and additional text adde
Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons
Mechanical allodynia is a major symptom of neuropathic pain whereby innocuous touch evokes severe pain. Here we identify a population of peripheral sensory neurons expressing TrkB that are both necessary and sufficient for producing pain from light touch after nerve injury in mice. Mice in which TrkB-Cre-expressing neurons are ablated are less sensitive to the lightest touch under basal conditions, and fail to develop mechanical allodynia in a model of neuropathic pain. Moreover, selective optogenetic activation of these neurons after nerve injury evokes marked nociceptive behavior. Using a phototherapeutic approach based upon BDNF, the ligand for TrkB, we perform molecule-guided laser ablation of these neurons and achieve long-term retraction of TrkB-positive neurons from the skin and pronounced reversal of mechanical allodynia across multiple types of neuropathic pain. Thus we identify the peripheral neurons which transmit pain from light touch and uncover a novel pharmacological strategy for its treatment
Beta Cells within Single Human Islets Originate from Multiple Progenitors
BACKGROUND: In both humans and rodents, glucose homeostasis is controlled by micro-organs called islets of Langerhans composed of beta cells, associated with other endocrine cell types. Most of our understanding of islet cell differentiation and morphogenesis is derived from rodent developmental studies. However, little is known about human islet formation. The lack of adequate experimental models has restricted the study of human pancreatic development to the histological analysis of different stages of pancreatic development. Our objective was to develop a new experimental model to (i) transfer genes into developing human pancreatic cells and (ii) validate gene transfer by defining the clonality of developing human islets. METHODS AND FINDINGS: In this study, a unique model was developed combining ex vivo organogenesis from human fetal pancreatic tissue and cell type-specific lentivirus-mediated gene transfer. Human pancreatic progenitors were transduced with lentiviruses expressing GFP under the control of an insulin promoter and grafted to severe combined immunodeficient mice, allowing human beta cell differentiation and islet morphogenesis. By performing gene transfer at low multiplicity of infection, we created a chimeric graft with a subpopulation of human beta cells expressing GFP and found both GFP-positive and GFP-negative beta cells within single islets. CONCLUSION: The detection of both labeled and unlabeled beta cells in single islets demonstrates that beta cells present in a human islet are derived from multiple progenitors thus providing the first dynamic analysis of human islet formation during development. This human transgenic-like tool can be widely used to elucidate dynamic genetic processes in human tissue formation
Diabetes-Specific Nutrition Algorithm: A Transcultural Program to Optimize Diabetes and Prediabetes Care
Type 2 diabetes (T2D) and prediabetes have a major global impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. To mitigate this disease burden, interventions of proven effectiveness must be used. Evidence shows that nutrition therapy improves glycemic control and reduces the risks of diabetes and its complications. Accordingly, diabetes-specific nutrition therapy should be incorporated into comprehensive patient management programs. Evidence-based recommendations for healthy lifestyles that include healthy eating can be found in clinical practice guidelines (CPGs) from professional medical organizations. To enable broad implementation of these guidelines, recommendations must be reconstructed to account for cultural differences in lifestyle, food availability, and genetic factors. To begin, published CPGs and relevant medical literature were reviewed and evidence ratings applied according to established protocols for guidelines. From this information, an algorithm for the nutritional management of people with T2D and prediabetes was created. Subsequently, algorithm nodes were populated with transcultural attributes to guide decisions. The resultant transcultural diabetes-specific nutrition algorithm (tDNA) was simplified and optimized for global implementation and validation according to current standards for CPG development and cultural adaptation. Thus, the tDNA is a tool to facilitate the delivery of nutrition therapy to patients with T2D and prediabetes in a variety of cultures and geographic locations. It is anticipated that this novel approach can reduce the burden of diabetes, improve quality of life, and save lives. The specific Southeast Asian and Asian Indian tDNA versions can be found in companion articles in this issue of Current Diabetes Reports
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