Detecting microRNA binding and siRNA off-target effects from expression data.

Sylamer is a method for detecting microRNA target and small interfering RNA off-target signals in 3' untranslated regions from a ranked gene list, sorted from upregulated to downregulated, after a microRNA perturbation or RNA interference experiment. The output is a landscape plot that tracks occurrence biases using hypergeometric P-values for all words across the gene ranking. We demonstrated the utility, speed and accuracy of this approach on several datasets

The influence of farmers' mental models on an agroforestry extension program in the Philippines

The influence of farmers' mental models on the success of an agroforestry extension program on Leyte Island in the Philippines was investigated. Knowledge of farmers' mental models and hence the likely acceptance of technology was used to inform the design of a hypothetically expanded program. To gain an insight into the reasons behind differing acceptance of extension assistance, data were collected and analysed from formal interviews, translated conversations and visual observations. The data provided a chain of evidence and triangulation between farmers' stated intentions and their actions. Farmers had little prior knowledge of nursery technology and were highly receptive to extension assistance which enabled them to develop high self-efficacy in seedling production. However, farmers' rejection of silvicultural advice to thin and prune existing plantations was predicated by existing attitudes to forest resource management. Farmers also expressed a strong preference for a low-cost and low-input approach to establishing timber trees. Visual observations of farmers' tree establishment practices indicated the existence of gaps in their knowledge of tree growth processes. This investigation illustrates the need to elicit farmers' mental models as a parallel enquiry to extension activities. If agroforestry extension is to be constructivist and participatory, accommodation of farmers' mental models and modification of program goals may be necessary. Relatively little is known about the reasons for farmers' acceptance or rejection of silviculture in Leyte and these results indicate that further research into the way that farmers' mental models filter and guide acceptance of advice may be worthwhile

Removal of AU Bias from Microarray mRNA Expression Data Enhances Computational Identification of Active MicroRNAs

Elucidation of regulatory roles played by microRNAs (miRs) in various biological networks is one of the greatest challenges of present molecular and computational biology. The integrated analysis of gene expression data and 3′-UTR sequences holds great promise for being an effective means to systematically delineate active miRs in different biological processes. Applying such an integrated analysis, we uncovered a striking relationship between 3′-UTR AU content and gene response in numerous microarray datasets. We show that this relationship is secondary to a general bias that links gene response and probe AU content and reflects the fact that in the majority of current arrays probes are selected from target transcript 3′-UTRs. Therefore, removal of this bias, which is in order in any analysis of microarray datasets, is of crucial importance when integrating expression data and 3′-UTR sequences to identify regulatory elements embedded in this region. We developed visualization and normalization schemes for the detection and removal of such AU biases and demonstrate that their application to microarray data significantly enhances the computational identification of active miRs. Our results substantiate that, after removal of AU biases, mRNA expression profiles contain ample information which allows in silico detection of miRs that are active in physiological conditions

Anterior interosseous nerve syndrome: retrospective analysis of 14 patients

Introduction: The anterior interosseous nerve (AIN) is a only motor nerve innervating the deep muscles of the forearm. Its compression is rare. We present a retrospective analysis of 14 patients with an AIN syndrome with a variety of clinical manifestations who underwent operative and conservative treatment. Patients and methods: Fourteen patients (six female, eight male, mean age 48 ± 9 years) were included. In six patients, the right limb was affected, and in eight patients the left limb. Conservative treatment was started for every patient. If no signs of recovery appeared within 3 months, operative exploration was performed. Final assessment was performed between 2 and 9 years after the onset of paralysis (mean duration of follow-up 46 ± 11 months). Patients were examined clinically for return of power, range of motion, pinch and grip strengths. Also the disability of the arm, shoulder, and hand (DASH) score was calculated. Results: Seven of our 14 patients had incomplete AIN palsy with isolated total loss of function of flexor pollicis longus (FPL), five of FPL and flexor digitorum profundus (FDP)1 simultaneously, and two of FDP1. Weakness of FDP2 could be seen in four patients. Pronator teres was paralysed in two patients. Pain in the forearm was present in nine patients. Four patients had predisposing factors. Eight patients treated conservatively exhibited spontaneous recovery from their paralysis during 3-12 months after the onset. In six patients, the AIN was explored 12 weeks after the initial symptoms and released from compressing structures. Thirteen patients showed good limb function. In one patient with poor result a tendon transfer was necessary. The DASH score of patients treated conservatively and operatively presented no significant difference. Conclusion: AIN syndrome can have different clinical manifestations. If no signs of spontaneous recovery appear within 12 weeks, operative treatment should be performed

Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function <it>in vivo</it>. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c.</p> <p>Methods</p> <p>In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth.</p> <p>Results</p> <p>These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival.</p> <p>Conclusions</p> <p>We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number can identify genes that are likely important for chemotherapy response. Our findings suggest a new approach to identify candidate genes that are critical for anti-tumor therapy.</p

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV