Fine-tuning implications for complementary dark matter and LHC SUSY searches

The requirement that SUSY should solve the hierarchy problem without undue fine-tuning imposes severe constraints on the new supersymmetric states. With the MSSM spectrum and soft SUSY breaking originating from universal scalar and gaugino masses at the Grand Unification scale, we show that the low-fine-tuned regions fall into two classes that will require complementary collider and dark matter searches to explore in the near future. The first class has relatively light gluinos or squarks which should be found by the LHC in its first run. We identify the multijet plus E_T^miss signal as the optimal channel and determine the discovery potential in the first run. The second class has heavier gluinos and squarks but the LSP has a significant Higgsino component and should be seen by the next generation of direct dark matter detection experiments. The combined information from the 7 TeV LHC run and the next generation of direct detection experiments can test almost all of the CMSSM parameter space consistent with dark matter and EW constraints, corresponding to a fine-tuning not worse than 1:100. To cover the complete low-fine-tuned region by SUSY searches at the LHC will require running at the full 14 TeV CM energy; in addition it may be tested indirectly by Higgs searches covering the mass range below 120 GeV.Comment: References added. Version accepted for publication in JHE

Constraints from muon g-2 and LFV processes in the Higgs Triplet Model

Constraints from the muon anomalous magnetic dipole moment and lepton flavor violating processes are translated into lower bounds on v_Delta*m_H++ in the Higgs Triplet Model by considering correlations through the neutrino mass matrix. The discrepancy of the sign of the contribution to the muon anomalous magnetic dipole moment between the measurement and the prediction in the model is clarified. It is shown that mu to e gamma, tau decays (especially, tau to mu e e), and the muonium conversion can give a more stringent bound on v_Delta*m_H++ than the bound from mu to eee which is expected naively to give the most stringent one.Comment: 18 pages, 16 figure

Methamphetamine withdrawal induces activation of CRF neurons in the brain stress system in parallel with an increased activity of cardiac sympathetic pathways.

Methamphetamine (METH) addiction is a major public health problem in some countries. There is evidence to suggest that METH use is associated with increased risk of developing cardiovascular problems. Here, we investigated the effects of chronic METH administration and withdrawal on the activation of the brain stress system and cardiac sympathetic pathways. Mice were treated with METH (2 mg/kg, i.p.) for 10 days and left to spontaneous withdraw for 7 days. The number of corticotrophin-releasing factor (CRF), c-Fos, and CRF/c-Fos neurons was measured by immunohistochemistry in the paraventricular nucleus of the hypothalamus (PVN) and the oval region of the bed nucleus of stria terminalis (ovBNST), two regions associated with cardiac sympathetic control. In parallel, levels of catechol-o-methyl-transferase (COMT), tyrosine hydroxylase (TH), and heat shock protein 27 (Hsp27) were measured in the heart. In the brain, chronic-METH treatment enhanced the number of c-Fos neurons and the CRF neurons with c-Fos signal (CRF+/c-Fos+) in PVN and ovBNST. METH withdrawal increased the number of CRF+neurons. In the heart, METH administration induced an increase in soluble (S)-COMT and membrane-bound (MB)-COMT without changes in phospho (p)-TH, Hsp27, or pHsp27. Similarly, METH withdrawal increased the expression of S- and MB-COMT. In contrast to chronic treatment, METH withdrawal enhanced levels of (p)TH and (p)Hsp27 in the heart. Overall, our results demonstrate that chronic METH administration and withdrawal activate the brain CRF systems associated with the heart sympathetic control and point towards a METH withdrawal induced activation of sympathetic pathways in the heart. Our findings provide further insight in the mechanism underlining the cardiovascular risk associated with METH use and proposes targets for its treatment

Assessment of two malaria rapid diagnostic tests in children under five years of age, with follow-up of false-positive pLDH test results, in a hyperendemic falciparum malaria area, Sierra Leone

ABSTRACT: BACKGROUND: Most malaria rapid diagnostic tests (RDTs) use HRP2 detection, including Paracheck-Pf(R), but their utility is limited by persistent false positivity after treatment. PLDH-based tests become negative more quickly, but sensitivity has been reported below the recommended standard of 90%. A new pLDH test, CareStartTM three-line P.f/PAN-pLDH, claims better sensitivity with continued rapid conversion to negative. The study aims were to 1) compare sensitivity and specificity of CareStartTM to Paracheck-Pf(R) to diagnose falciparum malaria in children under five years of age, 2) assess how quickly false-positive CareStartTM tests become negative and 3) evaluate ease of use and inter-reader agreement of both tests. METHODS: Participants were included if they were aged between two and 59 months, presenting to a Medecins Sans Frontieres community health centre in eastern Sierra Leone with suspected malaria defined as fever (axillary temperature > 37.5degreesC) and/or history of fever in the previous 72 hours and no signs of severe disease. The same capillary blood was used for the RDTs and the blood slide, the latter used as the gold standard reference. All positive participants were treated with supervised artesunate and amodiaquine treatment for three days. Participants with a persistent false-positive CareStartTM, but a negative blood slide on Day 2, were followed with repeated CareStartTM and blood slide tests every seven days until CareStartTM became negative or a maximum of 28 days. RESULTS: Sensitivity of CareStartTM was 99.4% (CI 96.8-100.0, 168/169) and of Paracheck-Pf(R), 98.8% (95% CI 95.8-99.8, 167/169). Specificity of CareStartTM was 96.0% (CI 91.9-98.4, 167/174) and of Paracheck-Pf(R), 74.7% (CI 67.6-81.0, 130/174) (p<0.001). Neither test showed any change in sensitivity with decreasing parasitaemia. Of the 155 eligible follow-up CareStartTM participants, 63.9% (99/155) had a false-positive test on day 2, 21.3% (33/155) on day 7, 5.8% (9/155) on day 14, 1.9% (3/155) on day 21 and 0.6% (1/155) on day 28. The median time for test negativity was seven days. CareStartTM was as easy to use and interpret as Paracheck-Pf(R) with excellent inter-reader agreement. CONCLUSIONS: Both RDTs were highly sensitive, met WHO standards for the detection of falciparum malaria monoinfections where parasitaemia was >100 parasites/mul and were easy to use. CareStartTM persistent false positivity decreased quickly after successful anti-malarial treatment, making it a good choice for a RDT for a hyperendemic falciparum malaria area

Proteomics of industrial fungi: trends and insights for biotechnology

Filamentous fungi are widely known for their industrial applications, namely, the production of food-processing enzymes and metabolites such as antibiotics and organic acids. In the past decade, the full genome sequencing of filamentous fungi increased the potential to predict encoded proteins enormously, namely, hydrolytic enzymes or proteins involved in the biosynthesis of metabolites of interest. The integration of genome sequence information with possible phenotypes requires, however, the knowledge of all the proteins in the cell in a system-wise manner, given by proteomics. This review summarises the progress of proteomics and its importance for the study of biotechnological processes in filamentous fungi. A major step forward in proteomics was to couple protein separation with high-resolution mass spectrometry, allowing accurate protein quantification. Despite the fact that most fungal proteomic studies have been focused on proteins from mycelial extracts, many proteins are related to processes which are compartmentalised in the fungal cell, e.g. β-lactam antibiotic production in the microbody. For the study of such processes, a targeted approach is required, e.g. by organelle proteomics. Typical workflows for sample preparation in fungal organelle proteomics are discussed, including homogenisation and sub-cellular fractionation. Finally, examples are presented of fungal organelle proteomic studies, which have enlarged the knowledge on areas of interest to biotechnology, such as protein secretion, energy production or antibiotic biosynthesis

Using simple artificial intelligence methods for predicting amyloidogenesis in antibodies

<p>Abstract</p> <p>Background</p> <p>All polypeptide backbones have the potential to form amyloid fibrils, which are associated with a number of degenerative disorders. However, the likelihood that amyloidosis would actually occur under physiological conditions depends largely on the amino acid composition of a protein. We explore using a naive Bayesian classifier and a weighted decision tree for predicting the amyloidogenicity of immunoglobulin sequences.</p> <p>Results</p> <p>The average accuracy based on leave-one-out (LOO) cross validation of a Bayesian classifier generated from 143 amyloidogenic sequences is 60.84%. This is consistent with the average accuracy of 61.15% for a holdout test set comprised of 103 AM and 28 non-amyloidogenic sequences. The LOO cross validation accuracy increases to 81.08% when the training set is augmented by the holdout test set. In comparison, the average classification accuracy for the holdout test set obtained using a decision tree is 78.64%. Non-amyloidogenic sequences are predicted with average LOO cross validation accuracies between 74.05% and 77.24% using the Bayesian classifier, depending on the training set size. The accuracy for the holdout test set was 89%. For the decision tree, the non-amyloidogenic prediction accuracy is 75.00%.</p> <p>Conclusions</p> <p>This exploratory study indicates that both classification methods may be promising in providing straightforward predictions on the amyloidogenicity of a sequence. Nevertheless, the number of available sequences that satisfy the premises of this study are limited, and are consequently smaller than the ideal training set size. Increasing the size of the training set clearly increases the accuracy, and the expansion of the training set to include not only more derivatives, but more alignments, would make the method more sound. The accuracy of the classifiers may also be improved when additional factors, such as structural and physico-chemical data, are considered. The development of this type of classifier has significant applications in evaluating engineered antibodies, and may be adapted for evaluating engineered proteins in general.</p

Charged Lepton Flavour Violating Radiative Decays ℓi→ℓj+γ\ell_i \to \ell_j + \gamma in See-Saw Models with A4A_4 Symmetry

The charged lepton flavour violating (LFV) radiative decays, $\mu\to e+\gamma$, $\tau\to \mu+\gamma$ and $\tau\to e +\gamma$ are investigated in a class of supersymmetric $A_4$ models with three heavy right-handed (RH) Majorana neutrinos, in which the lepton (neutrino) mixing is predicted to leading order (LO) to be tri-bimaximal. The light neutrino masses are generated via the type I see-saw mechanism. The analysis is done within the framework of the minimal supergravity (mSUGRA) scenario, which provides flavour universal boundary conditions at the scale of grand unification $M_X \approx 2 \times 10^{16}$ GeV. Detailed predictions for the rates of the three LFV decays are obtained in two explicit realisations of the $A_4$ models due to Altarelli and Feruglio and Altarelli and Meloni, respectively.Comment: Results unchanged, minor improvements made; version accepted for publication in JHE

The Simons Observatory: Science goals and forecasts

The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands: 27, 39, 93, 145, 225 and 280 GHz. The initial configuration of SO will have three small-aperture 0.5-m telescopes (SATs) and one large-aperture 6-m telescope (LAT), with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The SATs will target the largest angular scales observable from Chile, mapping ~10% of the sky to a white noise level of 2 $\mu$K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, $r$, at a target level of $\sigma(r)=0.003$. The LAT will map ~40% of the sky at arcminute angular resolution to an expected white noise level of 6 $\mu$K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the LSST sky region and partially with DESI. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources