Higher-order scalar interactions and SM vacuum stability

Investigation of the structure of the Standard Model effective potential at very large field strengths opens a window towards new phenomena and can reveal properties of the UV completion of the SM. The map of the lifetimes of the vacua of the SM enhanced by nonrenormalizable scalar couplings has been compiled to show how new interactions modify stability of the electroweak vacuum. Whereas it is possible to stabilize the SM by adding Planck scale suppressed interactions and taking into account running of the new couplings, the generic effect is shortening the lifetime and hence further destabilisation of the SM electroweak vacuum. These findings have been illustrated with phase diagrams of modified SM-like models. It has been demonstrated that stabilisation can be achieved by lowering the suppression scale of higher order operators while picking up such combinations of new couplings, which do not deepen the new minima of the potential. Our results show the dependence of the lifetime of the electroweak minimum on the magnitude of the new couplings, including cases with very small couplings (which means very large effective suppression scale) and couplings vastly different in magnitude (which corresponds to two different suppression scales).Comment: plain Latex, 9 figure

Novel and promising compounds to treat Cryptosporidium parvum infections

No fully effective approved drug therapy exists for Cryptosporidium infections of immunocompetent and immunocompromised patients. Here, we investigated 11 benzimidazole derivatives carrying substituted thioalkyl and thiobenzyl groups at position 2 of benzimidazole nucleus and additional substituents at the benzene part of benzimidazole for inhibition of the in vitro growth of the intestinal protozoan parasite, Cryptosporidium parvum. Three of them, i.e., 5-carboxy-2-(4-nitrobenzylthio)-1H-benzimidazole, 5,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, and 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, (compounds 5, 7, and 8) were the most active (IC50 28–31 μM). The concentration of compounds 5, 7, and 8 that caused 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was comparable with those obtained for paromomycin

Novel and promising compounds to treat Cryptosporidium parvum infections

No fully effective approved drug therapy exists for Cryptosporidium infections of immunocompetent and immunocompromised patients. Here, we investigated 11 benzimidazole derivatives carrying substituted thioalkyl and thiobenzyl groups at position 2 of benzimidazole nucleus and additional substituents at the benzene part of benzimidazole for inhibition of the in vitro growth of the intestinal protozoan parasite, Cryptosporidium parvum. Three of them, i.e., 5-carboxy-2-(4-nitrobenzylthio)-1H-benzimidazole, 5,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, and 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, (compounds 5, 7, and 8) were the most active (IC50 28–31 μM). The concentration of compounds 5, 7, and 8 that caused 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was comparable with those obtained for paromomycin

Experimental system to displace radioisotopes from upper to deeper soil layers: chemical research

BACKGROUND: Radioisotopes are introduced into the environment following nuclear power plant accidents or nuclear weapons tests. The immobility of these radioactive elements in uppermost soil layers represents a problem for human health, since they can easily be incorporated in the food chain. Preventing their assimilation by plants may be a first step towards the total recovery of contaminated areas. METHODS: The possibility of displacing radionuclides from the most superficial soil layers and their subsequent stabilisation at lower levels were investigated in laboratory trials. An experimental system reproducing the environmental conditions of contaminated areas was designed in plastic columns. A radiopolluted soil sample was treated with solutions containing ions normally used in fertilisation (NO(3)(-), NH(4)(+), PO(4)(--- )and K(+)). RESULTS: Contaminated soils treated with an acid solution of ions NO(3)(-), PO(4)(--- )and K(+), undergo a reduction of radioactivity up to 35%, after a series of washes which simulate one year's rainfall. The capacity of the deepest soil layers to immobilize the radionuclides percolated from the superficial layers was also confirmed. CONCLUSION: The migration of radionuclides towards deeper soil layers, following chemical treatments, and their subsequent stabilization reduces bioavailability in the uppermost soil horizon, preventing at the same time their transfer into the water-bearing stratum

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries

The present study examined the hypothesis that potassium ions act as an endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in small mesenteric arteries displaying myogenic tone. Small mesenteric arteries isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg. After developing myogenic tone, responses to raising extracellular potassium were compared to those obtained with ACh (in the presence of nitric oxide synthase and cyclo- oxygenase inhibitors). The effects of barium and ouabain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined. The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries. Rat small mesenteric arteries developed myogenic tone when pressurised. On the background of vascular tone set by a physiological stimulus (i.e pressure), ACh fully dilated the small arteries in a concentration-dependent manner. This response was relatively insensitive to the combination of barium and ouabain, and insensitive to capsaicin. Raising extracellular potassium produced a more inconsistent and modest vasodilator response in pressurised small mesenteric arteries. Responses to raising extracellular potassium were sensitive to capsaicin, and the combination of barium and ouabain. ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not. These data indicate that K+ is not the EDHF released in response to ACh in myogenically active rat mesenteric small arteries. Since the hyperpolarization produced by ACh was sensitive to carbenoxolone, gap junctions are the likely mediator of EDH responses under physiological conditions

Nanometer Sized Silver Particles Embedded Silica Particles—Spray Method

Spherical shaped, nanometer to micro meter sized silica particles were prepared in a homogeneous nature by spray technique. Silver nanoparticles were produced over the surface of the silica grains in a harmonized manner. The size of silver and silica particles was effectively controlled by the precursors and catalysts. The electrostatic repulsion among the silica spheres and the electro static attraction between silica spheres and silver particles make the synchronized structure of the synthesized particles and the morphological images are revealed by transmission electron microscope. The silver ions are reduced by sodium borohydride. Infra red spectroscopy and X-ray photoelectron spectroscopy analysis confirm the formation of silver–silica composite particles. Thermal stability of the prepared particles obtained from thermal analysis ensures its higher temperature applications. The resultant silver embedded silica particles can be easily suspended in diverse solvents and would be useful for variety of applications

Valproate, thalidomide and ethyl alcohol alter the migration of HTR-8/SVneo cells

BACKGROUND: Valproate, thalidomide and alcohol (ethanol) exposure during the first trimester of pregnancy is known to cause several developmental disorders. All these teratogens are known to pass the placental barrier and interfere directly with the normal development of the fetus. However, these teratogens also alter the formation and function of the placenta itself which may in turn affect the proper nourishment and development of the fetus. Optimum development of the placenta requires adequate invasion of trophoblast into the maternal uterine tissues. Changes in the migratory behavior of trophoblast by maternal exposure to these teratogens during placentogenesis may therefore alter the structure and function of the placenta. METHODS: In the present study, the effects of sodium valproate, thalidomide and alcohol on the migration of human first trimester trophoblast cell line (HTR-8/SVneo) were examined in vitro. Cells were cultured in the wells of 48-well culture plates as mono or multilayers. Circular patches of cells were removed from the center of the wells by suction, and the migration of cells into the wound was studied using microscopy. Effects of low and high concentrations of valproate, thalidomide and alcohol were examined on the healing of wounds and on the migration rate of cells by determining the wound areas at 0, 3, 6, 12, 24 and 48 h. Effects of drugs and alcohol on the proliferation and the expression levels of integrin subunits beta1 and alpha5 in cells were examined. RESULTS: The migration rates of trophoblast differed between wounds created in mono and multilayers of cells. Exposure to teratogens altered the migration of trophoblast into mono and multilayer wounds. The effects of valproate, thalidomide and alcohol on the proliferation of cells during the rapid migratory phase were mild. Drug exposure caused significant changes in the expression levels of beta1 and alpha5 integrin subunits. CONCLUSION: Results suggest that exposure to valproate, thalidomide or alcohol during the first trimester of pregnancy may change the ultrastructure of the placenta by altering the migration of trophoblast cells and this effect may be mediated by drug- or alcohol-induced changes in the expression levels of beta1 and alpha5 integrin subunits

Patient adherence to medical treatment: a review of reviews

BACKGROUND: Patients' non-adherence to medical treatment remains a persistent problem. Many interventions to improve patient adherence are unsuccessful and sound theoretical foundations are lacking. Innovations in theory and practice are badly needed. A new and promising way could be to review the existing reviews of adherence to interventions and identify the underlying theories for effective interventions. That is the aim of our study. METHODS: The study is a review of 38 systematic reviews of the effectiveness of adherence interventions published between 1990 and 2005. Electronic literature searches were conducted in Medline, Psychinfo, Embase and the Cochrane Library. Explicit inclusion and exclusion criteria were applied. The scope of the study is patient adherence to medical treatment in the cure and care sector. RESULTS: Significant differences in the effectiveness of adherence interventions were found in 23 of the 38 systematic reviews. Effective interventions were found in each of four theoretical approaches to adherence interventions: technical, behavioural, educational and multi-faceted or complex interventions. Technical solutions, such as a simplification of the regimen, were often found to be effective, although that does not count for every therapeutic regimen.Overall, our results show that, firstly, there are effective adherence interventions without an explicit theoretical explanation of the operating mechanisms, for example technical solutions. Secondly, there are effective adherence interventions, which clearly stem from the behavioural theories, for example incentives and reminders. Thirdly, there are other theoretical models that seem plausible for explaining non-adherence, but not very effective in improving adherence behaviour. Fourthly, effective components within promising theories could not be identified because of the complexity of many adherence interventions and the lack of studies that explicitly compare theoretical components. CONCLUSION: There is a scarcity of comparative studies explicitly contrasting theoretical models or their components. The relative weight of these theories and the effective components in the interventions designed to improve adherence, need to be assessed in future studies. (aut.ref.

TRPA1- FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

YesRecent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD) where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline rich motif. Here, we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2 hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.Faculty of Biological Sciences at the University of Leeds, Wellcome Trust Seed Award, Royal Society Research Grant RG150100, MR/K021303/1, Swedish Research Council (2014-3801) and the Medical Faculty at Lund University