Dirac Leptogenesis with a Non-anomalous U(1)′U(1)^{\prime} Family Symmetry

We propose a model for Dirac leptogenesis based on a non-anomalous $U(1)^{\prime}$ gauged family symmetry. The anomaly cancellation conditions are satisfied with no new chiral fermions other than the three right-handed neutrinos, giving rise to stringent constraints among the charges. Realistic masses and mixing angles are obtained for all fermions. The model predicts neutrinos of the Dirac type with naturally suppressed masses. Dirac leptogenesis is achieved through the decay of the flavon fields. The cascade decays of the vector-like heavy fermions in the Froggatt-Nielsen mechanism play a crucial role in the separation of the primodial lepton numbers. We find that a large region of parameter space of the model gives rise to a sufficient cosmological baryon number asymmetry through Dirac leptogenesis.Comment: 8 pages, 8 figures, version to appear in JHE

F-theory and Neutrinos: Kaluza-Klein Dilution of Flavor Hierarchy

We study minimal implementations of Majorana and Dirac neutrino scenarios in F-theory GUT models. In both cases the mass scale of the neutrinos m_nu ~ (M_weak)^2/M_UV arises from integrating out Kaluza-Klein modes, where M_UV is close to the GUT scale. The participation of non-holomorphic Kaluza-Klein mode wave functions dilutes the mass hierarchy in comparison to the quark and charged lepton sectors, in agreement with experimentally measured mass splittings. The neutrinos are predicted to exhibit a "normal" mass hierarchy, with masses m_3,m_2,m_1 ~ .05*(1,(alpha_GUT)^(1/2),alpha_GUT) eV. When the interactions of the neutrino and charged lepton sectors geometrically unify, the neutrino mixing matrix exhibits a mild hierarchical structure such that the mixing angles theta_23 and theta_12 are large and comparable, while theta_13 is expected to be smaller and close to the Cabibbo angle: theta_13 ~ theta_C ~ (alpha_GUT)^(1/2) ~ 0.2. This suggests that theta_13 should be near the current experimental upper bound.Comment: v2: 83 pages, 10 figures, references adde

Stem cell differentiation increases membrane-actin adhesion regulating cell blebability, migration and mechanics

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/K. S. is funded by an EPSRC PhD studentship. S.T. is funded by an EU Marie Curie Intra European Fellowship (GENOMICDIFF)

A Discrete Choice Experiment to assess patients’ preferences for HIV treatment in the rural population in Colombia

"Aim: To elicit patients’ preferences for HIV treatment of the rural population in Colombia. Methods: A discrete choice experiment (DCE), conducted in a HIV clinic in Bogotá, was used to examine the trade-off between five HIV treatment attributes: effect on life expectancy, effect on physical activity, risk of moderate side-effects, accessibility to clinic, and economic costs to access controls. Attributes selection was based on literature review, expert consultation and a focus group with six patients. An efficient experimental design was used to define two versions of the questionnaire with each of 12 choice sets and a dominance task was added to check reliability. A mixed logit model was then used to analyse the data and sub-group analyses were conducted on the basis of age, gender, education, and sexual preference. Results: A total of 129 HIV patients were included for analysis. For all treatment attributes, significant differences between at least two levels were observed, meaning that all attributes were significant predictors of choice. Patients valued the effect on physical activity (conditional relative importance of 27.5%) and the effect on life expectancy (26.0%) the most. Sub-group analyses regard age and education showed significant differences: younger patients and high educated patients valued the effect on physical activity the most important, whereas older patients mostly valued the effect on life expectancy and low educated patients mostly valued the accessibility to clinic. Limitations: One potential limitation is selection bias, as only patients from one HIV clinic were reached. Additionally, questionnaires were partly administered in the waiting rooms, which potentially led to noise in the data. Conclusions: This study suggests that all HIV treatment characteristics included in this DCE were important and that HIV patients from rural Colombia valued short-term efficacy (i.e. effect on physical activity) and long-term efficacy (i.e. effect on life expectancy) the most. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor and Francis Group.

A Discrete Choice Experiment to assess patients’ preferences for HIV treatment in the urban population in Colombia

Aim: This study aimed to assess patients' preferences for HIV treatment in an urban Colombian population. Methods: A Discrete Choice Experiment (DCE) was conducted. Urban Colombian HIV patients were asked to repetitively choose between two hypothetical treatments that differ in regard to five attributes 'effect on life expectancy', 'effect on physical activity', 'risk of moderate side effects, 'accessibility to clinic' and 'economic cost to access controls'. Twelve choice sets were made using an efficient design. A Mixed Logit Panel Model was used for the analysis and subgroup analyses were performed according to age, gender, education level and sexual preference. Results: A total of 224 HIV patients were included. All attributes were significant, indicating that there were differences between at least two levels of each attribute. Patients preferred to be able to perform all physical activity without difficulty, to have large positive effects on life expectancy, to travel less than 2 h, to have lower risk of side-effects and to have subsidized travel costs. The attributes 'effect on physical activity' and 'effects on life expectancy' were deemed the most important. Sub-analyses showed that higher educated patients placed more importance on the large positive effects of HIV treatment, and a more negative preference for subsidized travel cost (5% level). Limitations: A potential limitation is selection bias as it is difficult to make a systematic urban/rural division of respondents. Additional, questionnaires were partly administered in the waiting rooms, which potentially led to some noise in the data. Conclusions: Findings suggests that short-term efficacy (i.e. effect on physical activity) and long-term efficacy (i.e. effect on life expectancy) are the most important treatment characteristics for HIV urban patients in Colombia. Preference data could provide relevant information for clinical and policy decision-making to optimize HIV care

Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice

<p>Abstract</p> <p>Background</p> <p>Exposure to particulate matter (PM) air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract. PM can gain access to the gastrointestinal (GI) tract via swallowing of air or secretions from the upper airways or mucociliary clearance of inhaled particles.</p> <p>Methods</p> <p>We measured PM-induced cell death and mitochondrial ROS generation in Caco-2 cells stably expressing oxidant sensitive GFP localized to mitochondria in the absence or presence of an antioxidant. C57BL/6 mice were exposed to a very high dose of urban PM from Washington, DC (200 μg/mouse) or saline via gastric gavage and small bowel and colonic tissue were harvested for histologic evaluation, and RNA isolation up to 48 hours. Permeability to 4kD dextran was measured at 48 hours.</p> <p>Results</p> <p>PM induced mitochondrial ROS generation and cell death in Caco-2 cells. PM also caused oxidant-dependent NF-κB activation, disruption of tight junctions and increased permeability of Caco-2 monolayers. Mice exposed to PM had increased intestinal permeability compared with PBS treated mice. In the small bowel, colocalization of the tight junction protein, ZO-1 was lower in the PM treated animals. In the small bowel and colon, PM exposed mice had higher levels of IL-6 mRNA and reduced levels of ZO-1 mRNA. Increased apoptosis was observed in the colon of PM exposed mice.</p> <p>Conclusions</p> <p>Exposure to high doses of urban PM causes oxidant dependent GI epithelial cell death, disruption of tight junction proteins, inflammation and increased permeability in the gut <it>in vitro </it>and <it>in vivo</it>. These PM-induced changes may contribute to exacerbations of inflammatory disorders of the gut.</p

Ceftaroline Fosamil Therapy in Patients With Acute Bacterial Skin and Skin Structure Infections With Systemic Inflammatory Signs: A Retrospective Dose Comparison Across Three Pivotal Trials.

BACKGROUND: Post-hoc analysis compared pharmacokinetics and clinical outcomes of ceftaroline fosamil 600 mg every 12 (q12h) versus every 8 hours (q8h), in patients with acute bacterial skin and skin structure infections (ABSSSI) and signs of sepsis. METHODS: Clinical outcomes at test-of-cure in patients with ABSSSI and systemic inflammatory signs/systemic inflammatory response (SIRS), and ceftaroline minimum inhibitory concentrations (MICs) against baseline pathogens were compared between COVERS (ceftaroline fosamil 600 mg q8h, 2-h infusion) and the CANVAS 1 and 2 trials (ceftaroline fosamil 600 mg q12h, 1-h infusion). Ceftaroline exposures among patients in COVERS with or without markers of sepsis were compared using population pharmacokinetic (PK) modeling. RESULTS: In COVERS, 62% (312/506) and 41% (208/506) of ceftaroline fosamil-treated patients had ≥1 systemic sign or SIRS, respectively and 55% (378/693) and 22% (152/693), respectively in the CANVAS trials. Clinical cure rates for the modified intent-to-treat (MITT) population in COVERS and CANVAS were similar for ceftaroline fosamil-treated patients with ≥1 sign of sepsis (82% [255/312] and 85% [335/394]) and for those with SIRS (84% [168/199] and 85% [131/155]). Ceftaroline MIC distributions were similar across trials. Sepsis did not affect predicted individual steady-state ceftaroline exposures. CONCLUSIONS: Clinical cure rates in patients with ≥1 systemic inflammatory sign or SIRS were comparable for both ceftaroline fosamil dosage regimens. Pathogen susceptibilities to ceftaroline were similar across trials. Ceftaroline exposures were not affected by disease severity. Ceftaroline fosamil 600 mg q12h is a robust dosage regimen for most ABSSSI patients with sepsis

Exploring novel correlations in trilepton channels at the LHC for the minimal supersymmetric inverse seesaw model

We investigate signatures of the minimal supersymmetric inverse seesaw model at the large hadron collider (LHC) with three isolated leptons and large missing energy (3\ell + \mET or 2\ell + 1\tau + \mET, with \ell=e,\mu) in the final state. This signal has its origin in the decay of chargino-neutralino (\chpm1\ntrl2) pair, produced in pp collisions. The two body decays of the lighter chargino into a charged lepton and a singlet sneutrino has a characteristic decay pattern which is correlated with the observed large atmospheric neutrino mixing angle. This correlation is potentially observable at the LHC by looking at the ratios of cross sections of the trilepton + \mET channels in certain flavour specific modes. We show that even after considering possible leading standard model backgrounds these final states can lead to reasonable discovery significance at the LHC with both 7 TeV and 14 TeV center-of-mass energy.Comment: 28 pages, 9 .eps figures. 3 new figures and discussions on LHC observables added, minor modifications in text and in the abstract, 23 new references added, matches with the published version in JHE

Machine-learning of atomic-scale properties based on physical principles

We briefly summarize the kernel regression approach, as used recently in materials modelling, to fitting functions, particularly potential energy surfaces, and highlight how the linear algebra framework can be used to both predict and train from linear functionals of the potential energy, such as the total energy and atomic forces. We then give a detailed account of the Smooth Overlap of Atomic Positions (SOAP) representation and kernel, showing how it arises from an abstract representation of smooth atomic densities, and how it is related to several popular density-based representations of atomic structure. We also discuss recent generalisations that allow fine control of correlations between different atomic species, prediction and fitting of tensorial properties, and also how to construct structural kernels---applicable to comparing entire molecules or periodic systems---that go beyond an additive combination of local environments

Seesaw Neutrino Signals at the Large Hadron Collider

We discuss the scenario with gauge singlet fermions (right-handed neutrinos) accessible at the energy of the Large Hadron Collider. The singlet fermions generate tiny neutrino masses via the seesaw mechanism and also have sizable couplings to the standard-model particles. We demonstrate that these two facts, which are naively not satisfied simultaneously, are reconciled in the five-dimensional framework in various fashions, which make the seesaw mechanism observable. The collider signal of tri-lepton final states with transverse missing energy is investigated for two explicit examples of the observable seesaw, taking account of three types of neutrino mass spectrum and the constraint from lepton flavor violation. We find by showing the significance of signal discovery that the collider experiment has a potential to find signals of extra dimensions and the origin of small neutrino masses.Comment: 27 pages, 4 figure