Evaluation of measurement accuracies of the Higgs boson branching fractions in the International Linear Collider

Precise measurement of Higgs boson couplings is an important task for International Linear Collider (ILC) experiments and will facilitate the understanding of the particle mass generation mechanism. In this study, the measurement accuracies of the Higgs boson branching fractions to the $b$ and $c$ quarks and gluons, $\Delta Br(H\to b\bar{b},\sim c\bar{c},\sim gg)/Br$, were evaluated with the full International Large Detector model (\texttt{ILD\_00}) for the Higgs mass of 120 GeV at the center-of-mass (CM) energies of 250 and 350 GeV using neutrino, hadronic and leptonic channels and assuming an integrated luminosity of $250 {\rm fb^{-1}}$, and an electron (positron) beam polarization of -80% (+30%). We obtained the following measurement accuracies of the Higgs cross section times branching fraction ($\Delta (\sigma \cdot Br)/\sigma \cdot Br$) for decay of the Higgs into $b\bar{b}$, $c\bar{c}$, and $gg$; as 1.0%, 6.9%, and 8.5% at a CM energy of 250 GeV and 1.0%, 6.2%, and 7.3% at 350 GeV, respectively. After the measurement accuracy of the cross section ($\Delta\sigma/\sigma$) was corrected using the results of studies at 250 GeV and their extrapolation to 350 GeV, the derived measurement accuracies of the branching fractions ($\Delta Br/Br$) to $b\bar{b}$, $c\bar{c}$, and gg were 2.7%, 7.3%, and 8.9% at a CM energy of 250 GeV and 3.6%, 7.2%, and 8.1% at 350 GeV, respectively.Comment: 15 pages, 6 figure

One-pot synthesis and AFM imaging of a triangular aramide macrocycle

Macrocyclizations in exceptionally good yields were observed during the self-condensation of N-benzylated phenyl p-aminobenzoates in the presence of LiHMDS to yield three-membered cyclic aramides that adopt a triangular shape. An ortho-alkyloxy side chain on the N-benzyl protecting group is necessary for the macrocyclization to occur. Linear polymers are formed exclusively in the absence of this Li-chelating group. A model that explains the lack of formation of other cyclic congeners and the demand for an N-(o-alkoxybenzyl) protecting group is provided on the basis of DFT calculations. High-resolution AFM imaging of the prepared molecular triangles on a calcite(10.4) surface shows individual molecules arranged in groups of four due to strong surface templating effects and hydrogen bonding between the molecular triangles

Candidate-gene based GWAS identifies reproducible DNA markers for metabolic pyrethroid resistance from standing genetic variation in East African Anopheles gambiae.

Metabolic resistance to pyrethroid insecticides is widespread in Anopheles mosquitoes and is a major threat to malaria control. DNA markers would aid predictive monitoring of resistance, but few mutations have been discovered outside of insecticide-targeted genes. Isofemale family pools from a wild Ugandan Anopheles gambiae population, from an area where operational pyrethroid failure is suspected, were genotyped using a candidate-gene enriched SNP array. Resistance-associated SNPs were detected in three genes from detoxification superfamilies, in addition to the insecticide target site (the Voltage Gated Sodium Channel gene, Vgsc). The putative associations were confirmed for two of the marker SNPs, in the P450 Cyp4j5 and the esterase Coeae1d by reproducible association with pyrethroid resistance in multiple field collections from Uganda and Kenya, and together with the Vgsc-1014S (kdr) mutation these SNPs explained around 20% of variation in resistance. Moreover, the >20 Mb 2La inversion also showed evidence of association with resistance as did environmental humidity. Sequencing of Cyp4j5 and Coeae1d detected no resistance-linked loss of diversity, suggesting selection from standing variation. Our study provides novel, regionally-validated DNA assays for resistance to the most important insecticide class, and establishes both 2La karyotype variation and humidity as common factors impacting the resistance phenotype

NESH Regulates Dendritic Spine Morphology and Synapse Formation

Background: Dendritic spines are small membranous protrusions on the neuronal dendrites that receive synaptic input from axon terminals. Despite their importance for integrating the enormous information flow in the brain, the molecular mechanisms regulating spine morphogenesis are not well understood. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family, and its overexpression is known to reduce cell motility and tumor metastasis. NESH is prominently expressed in the brain, but its function there remains unknown. Methodology/Principal Findings: NESH was strongly expressed in the hippocampus and moderately expressed in the cerebral cortex, cerebellum and striatum, where it co-localized with the postsynaptic proteins PSD95, SPIN90 and F-actin in dendritic spines. Overexpression of NESH reduced numbers of mushroom-type spines and synapse density but increased thin, filopodia-like spines and had no effect on spine density. siRNA knockdown of NESH also reduced mushroom spine numbers and inhibited synapse formation but it increased spine density. The N-terminal region of NESH co-sedimented with filamentous actin (F-actin), which is an essential component of dendritic spines, suggesting this interaction is important for the maturation of dendritic spines. Conclusions/Significance: NESH is a novel F-actin binding protein that likely plays important roles in the regulation o

Mono- or Double-Site Phosphorylation Distinctly Regulates the Proapoptotic Function of Bax

Bax is the major multidomain proapoptotic molecule that is required for apoptosis. It has been reported that phosphorylation of Bax at serine(S) 163 or S184 activates or inactivates its proapoptotic function, respectively. To uncover the mechanism(s) by which phosphorylation regulates the proapoptotic function of Bax, a series of serine (S)→ alanine/glutamate (A/E) Bax mutants, including S163A, S184A, S163E, S184E, S163E/S184A (EA), S163A/S184E (AE), S163A/S184A (AA) and S163E/S184E (EE), were created to abrogate or mimic, respectively, either single or double-site phosphorylation. The compound Bax mutants (i.e. EA and AE) can flesh out the functional contribution of individual phosphorylation site(s). WT and each of these Bax mutants were overexpressed in Bax−/− MEF or lung cancer H157 cells and the proapoptotic activities were compared. Intriguingly, expression of any of Bax mutants containing the mutation S→A at S184 (i.e. S184A, EA or AA) represents more potent proapoptotic activity as compared to WT Bax in association with increased 6A7 epitope conformational change, mitochondrial localization/insertion and prolonged half-life. In contrast, all Bax mutants containing the mutation S→E at S184 (i.e. S184E, AE or EE) have a mobility-shift and fail to insert into mitochondrial membranes with decreased protein stability and less apoptotic activity. Unexpectedly, mutation either S→A or S→E at S163 site does not significantly affect the proapoptotic activity of Bax. These findings indicate that S184 but not S163 is the major phosphorylation site for functional regulation of Bax's activity. Therefore, manipulation of the phosphorylation status of Bax at S184 may represent a novel strategy for cancer treatment

Pregled AC-DC i DC-DC pretvarača za primjene u LED rasvjeti

High-Brightness Light Emitting Diodes (HB-LEDs) are considered the future trend in lighting not only due to their high efficiency and high reliability, but also due to their other outstanding characteristics: chromatic variety, shock and vibration resistance, etc. Nevertheless, they need the development of new power supplies especially designed for boosting and taking advantage of their aforementioned characteristics. Besides, their behaviour is completely different from the rest of lighting devices and, consequently, it should be also taken into account in the design of the converters used to drive them. As a result, many well-known topologies have been optimized or redesigned in order to be used in LED–lighting applications and many new topologies have come up in the recent years with the same purpose. In this paper, the main HB-LED characteristics will be explained, highlighting how they influence the design of their power supplies. After, the main topologies will be presented from the simplest to the most complex ones, analysing their advantages and disadvantages.Svjetleće diode s visokom razinom svjetline (HB-LED) smatraju se budućim trendom u rasvjeti zahvaljujući ne samo visokom stupnju efikasnosti i pouzdanosti, nego i njihovim izvanrednim svojstvima: raznolikost boja, otpornost na udarce i vibracije i sl. Ipak, s ciljem potpunog iskorištenja prethodno spomenutih svojstava, potrebno je razviti nove, posebno osmišljene izvore napajanja. Osim toga, ponašanje im se posve razlikuje od ostalih tipova rasvjete što je potrebno uzeti u obzir pri projektiranju pretvarača za njihovo napajanje. Kao posljedica toga, mnoge su poznate topologije pretvarača optimirane ili preoblikovane posebno za primjenu u LED rasvjeti, a zadnjih nekoliko godina mnoge nove su se tek pojavile. U ovom članku objašnjena su osnovna HB-LED svojstva naglašavajući njihov utjecaj na razvoj izvora napajanja. Uz to, prikazane su osnovne topologije, od najjednostavnijih do najsloženijih, ujedno analizirajući prednosti i nedostatke pojedinih

Activation of Wnt Signaling by Chemically Induced Dimerization of LRP5 Disrupts Cellular Homeostasis

Wnt signaling is crucial for a variety of biological processes, including body axis formation, planar polarity, stem cell maintenance and cellular differentiation. Therefore, targeted manipulation of Wnt signaling in vivo would be extremely useful. By applying chemical inducer of dimerization (CID) technology, we were able to modify the Wnt co-receptor, low-density lipoprotein (LDL)-receptor-related protein 5 (LRP5), to generate the synthetic ligand inducible Wnt switch, iLRP5. We show that iLRP5 oligomerization results in its localization to disheveled-containing punctate structures and sequestration of scaffold protein Axin, leading to robust β-catenin-mediated signaling. Moreover, we identify a novel LRP5 cytoplasmic domain critical for its intracellular localization and casein kinase 1-dependent β-catenin signaling. Finally, by utilizing iLRP5 as a Wnt signaling switch, we generated the Ubiquitous Activator of β-catenin (Ubi-Cat) transgenic mouse line. The Ubi-Cat line allows for nearly ubiquitous expression of iLRP5 under control of the H-2Kb promoter. Activation of iLRP5 in isolated prostate basal epithelial stem cells resulted in expansion of p63+ cells and development of hyperplasia in reconstituted murine prostate grafts. Independently, iLRP5 induction in adult prostate stroma enhanced prostate tissue regeneration. Moreover, induction of iLRP5 in male Ubi-Cat mice resulted in prostate tumor progression over several months from prostate hyperplasia to adenocarcinoma. We also investigated iLRP5 activation in Ubi-Cat-derived mammary cells, observing that prolonged activation results in mammary tumor formation. Thus, in two distinct experimental mouse models, activation of iLRP5 results in disruption of tissue homeostasis, demonstrating the utility of iLRP5 as a novel research tool for determining the outcome of Wnt activation in a precise spatially and temporally determined fashion