Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions

Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development

Skyrmion Multi-Walls

Skyrmion walls are topologically-nontrivial solutions of the Skyrme system which are periodic in two spatial directions. We report numerical investigations which show that solutions representing parallel multi-walls exist. The most stable configuration is that of the square $N$-wall, which in the $N\to\infty$ limit becomes the cubically-symmetric Skyrme crystal. There is also a solution resembling parallel hexagonal walls, but this is less stable.Comment: 7 pages, 1 figur

Higgs and Dark Matter Hints of an Oasis in the Desert

Recent LHC results suggest a standard model (SM)-like Higgs boson in the vicinity of 125 GeV with no clear indications yet of physics beyond the SM. At the same time, the SM is incomplete, since additional dynamics are required to accommodate cosmological dark matter (DM). In this paper we show that interactions between weak scale DM and the Higgs which are strong enough to yield a thermal relic abundance consistent with observation can easily destabilize the electroweak vacuum or drive the theory into a non-perturbative regime at a low scale. As a consequence, new physics--beyond the DM itself--must enter at a cutoff well below the Planck scale and in some cases as low as O(10 - 1000 TeV), a range relevant to indirect probes of flavor and CP violation. In addition, this cutoff is correlated with the DM mass and scattering cross-section in a parameter space which will be probed experimentally in the near term. Specifically, we consider the SM plus additional spin 0 or 1/2 states with singlet, triplet, or doublet electroweak quantum numbers and quartic or Yukawa couplings to the Higgs boson. We derive explicit expressions for the full two-loop RGEs and one-loop threshold corrections for these theories.Comment: 29 pages, 13 figure

Sphalerons and the Electroweak Phase Transition in Models with Higher Scalar Representations

In this work we investigate the sphaleron solution in a $SU(2)\times U(1)_X$ gauge theory, which also encompasses the Standard Model, with higher scalar representation(s) ($J^{(i)},X^{(i)}$). We show that the field profiles describing the sphaleron in higher scalar multiplet, have similar trends like the doublet case with respect to the radial distance. We compute the sphaleron energy and find that it scales linearly with the vacuum expectation value of the scalar field and its slope depends on the representation. We also investigate the effect of $U(1)$ gauge field and find that it is small for the physical value of the mixing angle, $\theta_{W}$ and resembles the case for the doublet. For higher representations, we show that the criterion for strong first order phase transition, $v_{c}/T_{c}>\eta$, is relaxed with respect to the doublet case, i.e. $\eta<1$.Comment: 20 pages, 5 figures & 1 table, published versio

Diretrizes para projeto de e-books com enfoque em crianças em fase de alfabetização

Neste artigo, os autores propõem-se a explorar de que modo o projeto de e-books voltados a crianças em fase de alfabetização pode ser aprimorado, de modo a fazer uso mais consciente dos recursos tecnológicos e, assim, melhorar a experiência de leitura infantil nesse contexto de ensino-aprendizagem. Para isso, partem de uma pesquisa bibliográfica dividida em duas partes: a primeira busca identificar características do público-alvo, suas capacidades e limitações no que diz respeito à leitura em suporte digital; a segunda, por sua vez, procura elucidar os aspectos técnicos envolvidos no projeto de livros digitais infantis, sob o enfoque do design, abordando tópicos como tipografia, ilustração e diagramação. Posteriormente, realizam uma análise de similares, em que observam e avaliam dez publicações digitais voltadas ao público infantil. A partir dos dados obtidos, propõem, então, diretrizes preliminares de projeto de e-books infantis e destacam alguns pontos de discussão, que são avaliados por seis especialistas, selecionados entre designers gráficos com experiência teórico/prática e especialistas em educação e/ou pedagogos. As diretrizes preliminares e pontos de discussão passam, então, por uma reavaliação, a partir dos apontamentos feitos pelo corpo de especialistas consultados. Os autores definem, por fim, como resultado da pesquisa, vinte diretrizes de projeto de e-books infantis que permitam ao designer envolvido em um projeto de e-book infantil explorar de forma adequada os recursos tecnológicos, aprimorando a qualidade técnica dos livros digitais em contexto de alfabetização – pretende-se, dessa forma, contribuir com os esforços acadêmicos na área, elucidando formas de se trabalhar a leitura em suporte digital como ferramenta efetiva em ambiente educacional

The Process " Pbar P -> E- E+ " with Polarized Initial Particles and Proton Form Factors in Time-Like Region

The discussion on the asymptotical behaviour of the form factors in the space-like and time-like regions have been corrected and clarified. Fig.3 has been replaced by an improved analysis of the data.Comment: DFTT 13/93. LaTeX file, 11 pages + 3 figures (included

Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions

Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.</jats:p

Vacuum stability, neutrinos, and dark matter

Motivated by the discovery hint of the Standard Model (SM) Higgs mass around 125 GeV at the LHC, we study the vacuum stability and perturbativity bounds on Higgs scalar of the SM extensions including neutrinos and dark matter (DM). Guided by the SM gauge symmetry and the minimal changes in the SM Higgs potential we consider two extensions of neutrino sector (Type-I and Type-III seesaw mechanisms) and DM sector (a real scalar singlet (darkon) and minimal dark matter (MDM)) respectively. The darkon contributes positively to the $\beta$ function of the Higgs quartic coupling $\lambda$ and can stabilize the SM vacuum up to high scale. Similar to the top quark in the SM we find the cause of instability is sensitive to the size of new Yukawa couplings between heavy neutrinos and Higgs boson, namely, the scale of seesaw mechanism. MDM and Type-III seesaw fermion triplet, two nontrivial representations of $SU(2)_{L}$ group, will bring the additional positive contributions to the gauge coupling $g_{2}$ renormalization group (RG) evolution and would also help to stabilize the electroweak vacuum up to high scale.Comment: 18 pages, 15 figures; published versio

EWPD Constraints on Flavor Symmetric Vector Fields

Electroweak precision data constraints on flavor symmetric vector fields are determined. The flavor multiplets of spin one that we examine are the complete set of fields that couple to quark bi-linears at tree level while not initially breaking the quark global flavor symmetry group. Flavor safe vector masses proximate to, and in some cases below, the electroweak symmetry breaking scale are found to be allowed. Many of these fields provide a flavor safe mechanism to explain the t tbar forward backward anomaly, and can simultaneously significantly raise the allowed values of the Standard Model Higgs mass consistent with electroweak precision data.Comment: Matches version published in JHE

Exploring alternative symmetry breaking mechanisms at the LHC with 7, 8 and 10 TeV total energy

In view of the annnouncement that in 2012 the LHC will run at 8 TeV, we study the possibility of detecting signals of alternative mechanisms of ElectroWeak Symmetry Breaking, described phenomenologically by unitarized models, at energies lower than 14 TeV. A complete calculation with six fermions in the final state is performed using the PHANTOM event generator. Our results indicate that at 8 TeV some of the scenarios with TeV scale resonances are likely to be identified while models with no resonances or with very heavy ones will be inaccessible, unless the available luminosity will be much higher than expected