Muon to electron conversion in the Littlest Higgs model with T-parity

Little Higgs models provide a natural explanation of the little hierarchy between the electroweak scale and a few TeV scale, where new physics is expected. Under the same inspiring naturalness arguments, this work completes a previous study on lepton flavor-changing processes in the Littlest Higgs model with T-parity exploring the channel that will eventually turn out to be the most sensitive, \mu-e conversion in nuclei. All one-loop contributions are carefully taken into account, results for the most relevant nuclei are provided and a discussion of the influence of the quark mixing is included. The results for the Ti nucleus are in good agreement with earlier work by Blanke et al., where a degenerate mirror quark sector was assumed. The conclusion is that, although this particular model reduces the tension with electroweak precision tests, if the restrictions on the parameter space derived from lepton flavor violation are taken seriously, the degree of fine tuning necessary to meet these constraints also disfavors this model.Comment: 26 pages, 7 figures, 4 tables; discussion improved, results unchanged, one reference added, version to appear in JHE

The Early Evolution of Biting–Chewing Performance in Hexapoda

Insects show a plethora of different mandible shapes. It was advocated that these mandible shapes are mainly a function of different feeding habits. This hypothesis was tested on a larger sampling of non-holometabolan biting–chewing insects with additional tests to understand the interplay of mandible function, feeding guild, and phylogeny. The results show that at the studied systematic level, variation in mandible biting–chewing effectivity is regulated to a large extent by phylogenetic history and the configuration of the mandible joints rather than the food preference of a given taxon. Additionally, lineages with multiple mandibular joints such as primary wingless hexapods show a wider functional space occupation of mandibular effectivity than dicondylic insects (= silverfish + winged insects) at significantly different evolutionary rates. The evolution and occupation of a comparably narrow functional performance space of dicondylic insects is surprising given the low effectivity values of this food uptake solution. Possible reasons for this relative evolutionary “stasis” are discussed

Do health systems delay the treatment of poor children? A qualitative study of child deaths in rural Tanzania.

Child mortality remains one of the major public-health problems in Tanzania. Delays in receiving and accessing adequate care contribute to these high rates. The literature on public health often focuses on the role of mothers in delaying treatment, suggesting that they contact the health system too late and that they prefer to treat their children at home, a perspective often echoed by health workers. Using the three-delay methodology, this study focus on the third phase of the model, exploring the delays experienced in receiving adequate care when mothers with a sick child contact a health-care facility. The overall objective is to analyse specific structural factors embedded in everyday practices at health facilities in a district in Tanzania which cause delays in the treatment of poor children and to discuss possible changes to institutions and social technologies. The study is based on qualitative fieldwork, including in-depth interviews with sixteen mothers who have lost a child, case studies in which patients were followed through the health system, and observations of more than a hundred consultations at all three levels of the health-care system. Data analysis took the form of thematic analysis. Focusing on the third phase of the three-delay model, four main obstacles have been identified: confusions over payment, inadequate referral systems, the inefficient organization of health services and the culture of communication. These impediments strike the poorest segment of the mothers particularly hard. It is argued that these delaying factors function as 'technologies of social exclusion', as they are embedded in the everyday practices of the health facilities in systematic ways. The interviews, case studies and observations show that it is especially families with low social and cultural capital that experience delays after having contacted the health-care system. Reductions of the various types of uncertainty concerning payment, improved referral practices and improved communication between health staff and patients would reduce some of the delays within health facilities, which might feedback positively into the other two phases of delay

An Alternating GluN1-2-1-2 Subunit Arrangement in Mature NMDA Receptors

NMDA receptors (NMDARs) form glutamate-gated ion channels that play a critical role in CNS physiology and pathology. Together with AMPA and kainate receptors, NMDARs are known to operate as tetrameric complexes with four membrane-embedded subunits associating to form a single central ion-conducting pore. While AMPA and some kainate receptors can function as homomers, NMDARs are obligatory heteromers composed of homologous but distinct subunits, most usually of the GluN1 and GluN2 types. A fundamental structural feature of NMDARs, that of the subunit arrangement around the ion pore, is still controversial. Thus, in a typical NMDAR associating two GluN1 and two GluN2 subunits, there is evidence for both alternating 1/2/1/2 and non-alternating 1/1/2/2 arrangements. Here, using a combination of electrophysiological and cross-linking experiments, we provide evidence that functional GluN1/GluN2A receptors adopt the 1/2/1/2 arrangement in which like subunits are diagonal to one another. Moreover, based on the recent crystal structure of an AMPA receptor, we show that in the agonist-binding and pore regions, the GluN1 subunits occupy a “proximal” position, closer to the central axis of the channel pore than that of GluN2 subunits. Finally, results obtained with reducing agents that differ in their membrane permeability indicate that immature (intracellular) and functional (plasma-membrane inserted) pools of NMDARs can adopt different subunit arrangements, thus stressing the importance of discriminating between the two receptor pools in assembly studies. Elucidating the quaternary arrangement of NMDARs helps to define the interface between the subunits and to understand the mechanism and pharmacology of these key signaling receptors

Heavy-light decay topologies as a new strategy to discover a heavy gluon

We study the collider phenomenology of the lightest Kaluza-Klein excitation of the gluon, G*, in theories with a warped extra dimension. We do so by means of a two-site effective lagrangian which includes only the lowest-lying spin-1 and spin-1/2 resonances. We point out the importance of the decays of G* to one SM plus one heavy fermion, that were overlooked in the previous literature. It turns out that, when kinematically allowed, such heavy-light decays are powerful channels for discovering the G*. In particular, we present a parton-level Montecarlo analysis of the final state Wtb that follows from the decay of G* to one SM top or bottom quark plus its heavy partner. We find that at \sqrt{s} = 7 TeV and with 10 fb^{-1} of integrated luminosity, the LHC can discover a KK gluon with mass in the range M_{G*} = (1.8 - 2.2) TeV if its coupling to a pair of light quarks is g_{G*qqbar} = (0.2-0.5) g_3. The same process is also competitive for the discovery of the top and bottom partners as well. We find, for example, that the LHC at \sqrt{s} = 7 TeV can discover a 1 TeV KK bottom quark with an integrated luminosity of (5.3 - 0.61) fb^{-1} for g_{G*qqbar} = (0.2-0.5) g_3.Comment: 36 pages, 13 figures. v2: a few typos corrected, comments added, version published in JHE

Event-related alpha suppression in response to facial motion

This article has been made available through the Brunel Open Access Publishing Fund.While biological motion refers to both face and body movements, little is known about the visual perception of facial motion. We therefore examined alpha wave suppression as a reduction in power is thought to reflect visual activity, in addition to attentional reorienting and memory processes. Nineteen neurologically healthy adults were tested on their ability to discriminate between successive facial motion captures. These animations exhibited both rigid and non-rigid facial motion, as well as speech expressions. The structural and surface appearance of these facial animations did not differ, thus participants decisions were based solely on differences in facial movements. Upright, orientation-inverted and luminance-inverted facial stimuli were compared. At occipital and parieto-occipital regions, upright facial motion evoked a transient increase in alpha which was then followed by a significant reduction. This finding is discussed in terms of neural efficiency, gating mechanisms and neural synchronization. Moreover, there was no difference in the amount of alpha suppression evoked by each facial stimulus at occipital regions, suggesting early visual processing remains unaffected by manipulation paradigms. However, upright facial motion evoked greater suppression at parieto-occipital sites, and did so in the shortest latency. Increased activity within this region may reflect higher attentional reorienting to natural facial motion but also involvement of areas associated with the visual control of body effectors. © 2014 Girges et al

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

Lepton flavor violation in the Simplest Little Higgs model

The flavor sector of Little Higgs models based on product groups, notably the Littlest Higgs with T parity (LHT), has been extensively studied and some amount of fine tuning was found to be required to meet the experimental constraints. However, no such attention has been paid to other classes of models. Here we analyze the phenomenology of flavor mixing in the lepton sector of a simple group model, the Simplest Little Higgs (SLH). We obtain the Feynman rules of the SLH in the 't Hooft-Feynman gauge up to the necessary order and calculate the leading contributions to the rare processes mu -> e gamma, mu -> eee and mu-e conversion in nuclei. We find results comparable to those of the LHT model, because in both cases they arise at the one-loop level. These require the flavor alignment of the Yukawa couplings of light and heavy leptons at the per cent level or an effective scale of around 10 TeV.Comment: 41 pages, 8 figures; minor changes and one reference added, version to appear in JHE

Natural products as starting points for future anti-malarial therapies: going back to our roots?

Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal medicinal products already used by the community. This first step forms a solid basis of observations, before moving to in vivo pharmacological characterization and ultimately identifying the active ingredient. A large part of the population uses herbal medicinal products despite limited numbers of well-controlled clinical studies. Increased awareness by the regulators and public health bodies of the need for safety information on herbal medicinal products also lends support to obtaining more clinical data on such products. Conclusions The relative paucity of new herbal medicinal product scaffolds active against malaria results discovered in recent years suggest it is time to re-evaluate the ‘smash and grab’ approach of randomly testing purified natural products and replace it with a patient-data led approach. This will require a change of perspective form many in the field. It will require an investment in standardisation in several areas, including: the ethnopharmacology and design and reporting of clinical observation studies, systems for characterizing anti-malarial activity of patient plasma samples ex vivo followed by chemical and pharmacological characterisation of extracts from promising sources. Such work falls outside of the core mandate of the product development partnerships, such as MMV, and so will require additional support. This call is timely, given the strong interest from researchers in disease endemic countries to support the research arm of a malaria eradication agenda. Para-national institutions such as the African Network for Drugs and Diagnostics Innovation (ANDi) will play a major role in facilitating the development of their natural products patrimony and possibly clinical best practice to bring forward new therapeutics. As in the past, with quinine, lapinone and artemisinin, once the activity of herbal medicinal products in humans is characterised, it can be used to identify new molecular scaffolds which will form the basis of the next generation of anti-malarial therapies.</p