Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that infects approximately 10–20 million people worldwide and causes an aggressive neoplasia (adult T-cell leukemia/lymphoma - ATL). Therapeutic approaches for the treatment of ATL have variable effectiveness and poor prognosis, thus requiring strategies to identify novel compounds with activity on infected cells. In this sense, we initially screened a small series of 25 1,2,3-triazole derivatives to discover cell proliferation inhibitors and apoptosis inducers in HTLV-1-infected T-cell line (MT-2) for further assessment of their effect on viral tax activity through inducible-tax reporter cell line (Jurkat LTR-GFP). Eight promising compounds (02, 05, 06, 13, 15, 21, 22 and 25) with activity ≥70% were initially selected, based on a suitable cell-based assay using resazurin reduction method, and evaluated towards cell cycle, apoptosis and Tax/GFP expression analyses through flow cytometry. Compound 02 induced S phase cell cycle arrest and compounds 05, 06, 22 and 25 promoted apoptosis. Remarkably, compounds 22 and 25 also reduced GFP expression in an inducible-tax reporter cell, which suggests an effect on Tax viral protein. More importantly, compounds 02, 22 and 25 were not cytotoxic in human hepatoma cell line (Huh-7). Therefore, the discovery of 3 active and non-cytotoxic compounds against HTLV-1-infected cells can potentially contribute, as an initial promising strategy, to the development process of new drugs against ATL

General analysis of signals with two leptons and missing energy at the Large Hadron Collider

A signal of two leptons and missing energy is challenging to analyze at the Large Hadron Collider (LHC) since it offers only few kinematical handles. This signature generally arises from pair production of heavy charged particles which each decay into a lepton and a weakly interacting stable particle. Here this class of processes is analyzed with minimal model assumptions by considering all possible combinations of spin 0, 1/2 or 1, and of weak iso-singlets, -doublets or -triplets for the new particles. Adding to existing work on mass and spin measurements, two new variables for spin determination and an asymmetry for the determination of the couplings of the new particles are introduced. It is shown that these observables allow one to independently determine the spin and the couplings of the new particles, except for a few cases that turn out to be indistinguishable at the LHC. These findings are corroborated by results of an alternative analysis strategy based on an automated likelihood test.Comment: 18 pages, 3 figures, LaTe

Supersymmetric Monojets at the Large Hadron Collider

Supersymmetric monojets may be produced at the Large Hadron Collider by the process qg -> squark neutralino_1 -> q neutralino_1 neutralino_1, leading to a jet recoiling against missing transverse momentum. We discuss the feasibility and utility of the supersymmetric monojet signal. In particular, we examine the possible precision with which one can ascertain the neutralino_1-squark-quark coupling via the rate for monojet events. Such a coupling contains information on the composition of the neutralino_1 and helps bound dark matter direct detection cross-sections and the dark matter relic density of the neutralino_1. It also provides a check of the supersymmetric relation between gauge couplings and gaugino-quark-squark couplings.Comment: 46 pages, 10 figures. The appendix has been rewritten to correct an error that appears in all previous versions of the appendix. This error has no effect on the results in the main body of the pape

Ecological Modeling of Aedes aegypti (L.) Pupal Production in Rural Kamphaeng Phet, Thailand

Background - Aedes aegypti (L.) is the primary vector of dengue, the most important arboviral infection globally. Until an effective vaccine is licensed and rigorously administered, Ae. aegypti control remains the principal tool in preventing and curtailing dengue transmission. Accurate predictions of vector populations are required to assess control methods and develop effective population reduction strategies. Ae. aegypti develops primarily in artificial water holding containers. Release recapture studies indicate that most adult Ae. aegypti do not disperse over long distances. We expect, therefore, that containers in an area of high development site density are more likely to be oviposition sites and to be more frequently used as oviposition sites than containers that are relatively isolated from other development sites. After accounting for individual container characteristics, containers more frequently used as oviposition sites are likely to produce adult mosquitoes consistently and at a higher rate. To this point, most studies of Ae. aegypti populations ignore the spatial density of larval development sites. Methodology - Pupal surveys were carried out from 2004 to 2007 in rural Kamphaeng Phet, Thailand. In total, 84,840 samples of water holding containers were used to estimate model parameters. Regression modeling was used to assess the effect of larval development site density, access to piped water, and seasonal variation on container productivity. A varying-coefficients model was employed to account for the large differences in productivity between container types. A two-part modeling structure, called a hurdle model, accounts for the large number of zeroes and overdispersion present in pupal population counts. Findings - The number of suitable larval development sites and their density in the environment were the primary determinants of the distribution and abundance of Ae. aegypti pupae. The productivity of most container types increased significantly as habitat density increased. An ecological approach, accounting for development site density, is appropriate for predicting Ae. aegypti population levels and developing efficient vector control program

LHC and lepton flavour violation phenomenology of a left-right extension of the MSSM

We study the phenomenology of a supersymmetric left-right model, assuming minimal supergravity boundary conditions. Both left-right and (B-L) symmetries are broken at an energy scale close to, but significantly below the GUT scale. Neutrino data is explained via a seesaw mechanism. We calculate the RGEs for superpotential and soft parameters complete at 2-loop order. At low energies lepton flavour violation (LFV) and small, but potentially measurable mass splittings in the charged scalar lepton sector appear, due to the RGE running. Different from the supersymmetric 'pure seesaw' models, both, LFV and slepton mass splittings, occur not only in the left- but also in the right slepton sector. Especially, ratios of LFV slepton decays, such as Br(${\tilde\tau}_R \to \mu \chi^0_1$)/Br(${\tilde\tau}_L \to \mu \chi^0_1$) are sensitive to the ratio of (B-L) and left-right symmetry breaking scales. Also the model predicts a polarization asymmetry of the outgoing positrons in the decay $\mu^+ \to e^+ \gamma$, A ~ [0,1], which differs from the pure seesaw 'prediction' A=1$. Observation of any of these signals allows to distinguish this model from any of the three standard, pure (mSugra) seesaw setups.Comment: 43 pages, 17 figure

Supersymmetric mass spectra and the seesaw type-I scale

We calculate supersymmetric mass spectra with cMSSM boundary conditions and a type-I seesaw mechanism added to explain current neutrino data. Using published, estimated errors on SUSY mass observables for a combined LHC+ILC analysis, we perform a theoretical $\chi^2$ analysis to identify parameter regions where pure cMSSM and cMSSM plus seesaw type-I might be distinguishable with LHC+ILC data. The most important observables are determined to be the (left) smuon and selectron masses and the splitting between them, respectively. Splitting in the (left) smuon and selectrons is tiny in most of cMSSM parameter space, but can be quite sizeable for large values of the seesaw scale, $m_{SS}$. Thus, for very roughly $m_{SS} \ge 10^{14}$ GeV hints for type-I seesaw might appear in SUSY mass measurements. Since our numerical results depend sensitively on forecasted error bars, we discuss in some detail the accuracies, which need to be achieved, before a realistic analysis searching for signs of type-I seesaw in SUSY spectra can be carried out.Comment: 17 pages, 7 figure

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies