577 research outputs found
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()/Br() 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 , 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 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,
. Thus, for very roughly 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
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