Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography

A key drug target for malaria has been the detoxification pathway of the iron containing molecule heme, which is the toxic byproduct of hemoglobin digestion. The cornerstone of heme detoxification is its sequestration into hemozoin crystals, but how this occurs remains uncertain. We report new results of in vivo rate of heme crystallization in the malaria parasite, based on a new technique to measure element specific concentrations at defined locations in cell ultrastructure. Specifically, a high resolution correlative combination of cryo soft X ray tomography has been developed to obtain 3D parasite ultrastructure with cryo X ray fluorescence microscopy to measure heme concentrations. Our results are consistent with a model for crystallization via the heme detoxification protein. Our measurements also demonstrate the presence of considerable amounts of non crystalline heme in the digestive vacuole, which we show is most likely contained in hemoglobin. These results suggest a tight coupling between hemoglobin digestion and heme crystallization, highlighting a new link in the crystallization pathway for drug developmen

Spatially and Financially Explicit Population Viability Analysis of Maculinea alcon in The Netherlands

Background The conservation of species structured in metapopulations involves an important dilemma of resource allocation: should investments be directed at restoring/enlarging habitat patches or increasing connectivity. This is still an open question for Maculinea species despite they are among the best studied and emblematic butterfly species, because none of the population dynamics models developed so far included dispersal. Methodology/Principal Findings We developed the first spatially and financially explicit Population Viability Analysis model for Maculinea alcon, using field data from The Netherlands. Implemented using the RAMAS/GIS platform, the model incorporated both local (contest density dependence, environmental and demographic stochasticities), and regional population dynamics (dispersal rates between habitat patches). We selected four habitat patch networks, contrasting in several basic features (number of habitat patches, their quality, connectivity, and occupancy rate) to test how these features are affecting the ability to enhance population viability of four basic management options, designed to incur the same costs: habitat enlargement, habitat quality improvement, creation of new stepping stone habitat patches, and reintroduction of captive-reared butterflies. The PVA model was validated by the close match between its predictions and independent field observations on the patch occupancy pattern. The four patch networks differed in their sensitivity to model parameters, as well as in the ranking of management options. Overall, the best cost-effective option was enlargement of existing habitat patches, followed by either habitat quality improvement or creation of stepping stones depending on the network features. Reintroduction was predicted to generally be inefficient, except in one specific patch network. Conclusions/Significance Our results underline the importance of spatial and regional aspects (dispersal and connectivity) in determining the impact of conservation actions, even for a species previously considered as sedentary. They also illustrate that failure to account for the cost of management scenarios can lead to very different conclusions

Computers in the Exam Room: Differences in Physician–Patient Interaction May Be Due to Physician Experience

BACKGROUND: The use of electronic medical records can improve the technical quality of care, but requires a computer in the exam room. This could adversely affect interpersonal aspects of care, particularly when physicians are inexperienced users of exam room computers. OBJECTIVE: To determine whether physician experience modifies the impact of exam room computers on the physician–patient interaction. DESIGN: Cross-sectional surveys of patients and physicians. SETTING AND PARTICIPANTS: One hundred fifty five adults seen for scheduled visits by 11 faculty internists and 12 internal medicine residents in a VA primary care clinic. MEASUREMENTS: Physician and patient assessment of the effect of the computer on the clinical encounter. MAIN RESULTS: Patients seeing residents, compared to those seeing faculty, were more likely to agree that the computer adversely affected the amount of time the physician spent talking to (34% vs 15%, P = 0.01), looking at (45% vs 24%, P = 0.02), and examining them (32% vs 13%, P = 0.009). Moreover, they were more likely to agree that the computer made the visit feel less personal (20% vs 5%, P = 0.017). Few patients thought the computer interfered with their relationship with their physicians (8% vs 8%). Residents were more likely than faculty to report these same adverse effects, but these differences were smaller and not statistically significant. CONCLUSION: Patients seen by residents more often agreed that exam room computers decreased the amount of interpersonal contact. More research is needed to elucidate key tasks and behaviors that facilitate doctor–patient communication in such a setting

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models

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

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

Monsoons: global energetics and local physics as drivers of past, present and future monsoons

Global constraints on momentum and energy govern the structure of the zonal mean tropical circulation and rainfall. The continental-scale monsoon systems are also facets of a momentum- and energy-constrained global circulation, but their modern and paleo variability deviates substantially from that of the longitudinal mean through mechanisms neither fully understood nor well simulated. A framework grounded in global constraints yet encompassing the complexities of monsoon dynamics is needed to identify the causes of mismatch between theory, models, and observations and, ultimately, improve regional climate projection. In a first step towards this goal, disparate regional processes must be distilled into gross measures of energy flow in and out of continents and from the surface to the tropopause, so that monsoon dynamics may be coherently diagnosed across modern and paleo observations and across idealized and comprehensive simulations. Accounting for zonal asymmetries in the circulation, land/ocean differences in surface fluxes, and the character of convective systems, such a monsoon framework would integrate our understanding at all relevant scales: from the fine details of how moisture and energy are lifted in the updrafts of thunderclouds, up to the global circulations