LET spectra measurements of charged particles in the P0006 experiment on LDEF

Measurements are under way of the charged particle radiation environment of the Long Duration Exposure Facility (LDEF) satellite using stacks of plastic nuclear track detectors (PNTD's) placed in different locations of the satellite. In the initial work the charge, energy, and linear energy transfer (LET) spectra of charged particles were measured with CR-39 double layer PNTD's located on the west side of the satellite (Experiment P0006). Primary and secondary stopping heavy ions were measured separately from the more energetic particles. Both trapped and galactic cosmic ray (GCR) particles are included, with the latter component being dominated by relativistic iron particles. The results from the P0006 experiment will be compared with similar measurements in other locations on LDEF with different orientation and shielding conditions. The remarkably detailed investigation of the charged particle radiation environment of the LDEF satellite will lead to a better understanding of the radiation environment of the Space Station Freedom. It will enable more accurate prediction of single event upsets (SEU's) in microelectronics and, especially, more accurate assessment of the risk - contributed by different components of the radiation field (GCR's, trapped protons, secondaries and heavy recoils, etc.) - to the health and safety of crew members

Hot dense capsule implosion cores produced by z-pinch dynamic hohlraum radiation

Hot dense capsule implosions driven by z-pinch x-rays have been measured for the first time. A ~220 eV dynamic hohlraum imploded 1.7-2.1 mm diameter gas-filled CH capsules which absorbed up to ~20 kJ of x-rays. Argon tracer atom spectra were used to measure the Te~ 1keV electron temperature and the ne ~ 1-4 x10^23 cm-3 electron density. Spectra from multiple directions provide core symmetry estimates. Computer simulations agree well with the peak compression values of Te, ne, and symmetry, indicating reasonable understanding of the hohlraum and implosion physics.Comment: submitted to Phys. Rev. Let

Duplication of clostridial binding domains for enhanced macromolecular delivery into neurons

Neurological diseases constitute a quarter of global disease burden and are expected to rise worldwide with the ageing of human populations. There is an increasing need to develop new molecular systems which can deliver drugs specifically into neurons, non-dividing cells meant to last a human lifetime. Neuronal drug delivery must rely on agents which can recognise neurons with high specificity and affinity. Here we used a recently introduced ‘stapling’ system to prepare macromolecules carrying duplicated binding domains from the clostridial family of neurotoxins. We engineered individual parts of clostridial neurotoxins separately and combined them using a strong alpha-helical bundle. We show that combining two identical binding domains of tetanus and botulinum type D neurotoxins, in a sterically defined way by protein stapling, allows enhanced intracellular delivery of molecules into neurons. We also engineered a botulinum neurotoxin type C variant with a duplicated binding domain which increased enzymatic delivery compared to the native type C toxin. We conclude that duplication of the binding parts of tetanus or botulinum neurotoxins will allow production of high avidity agents which could deliver imaging reagents and large therapeutic enzymes into neurons with superior efficiency

Electronic structure of the candidate 2D Dirac semimetal SrMnSb2: a combined experimental and theoretical study

SrMnSb$_2$ is suggested to be a magnetic topological semimetal. It contains square, 2D Sb planes with non-symmorphic crystal symmetries that could protect band crossings, offering the possibility of a quasi-2D, robust Dirac semi-metal in the form of a stable, bulk (3D) crystal. Here, we report a combined and comprehensive experimental and theoretical investigation of the electronic structure of SrMnSb$_2$, including the first ARPES data on this compound. SrMnSb$_2$ possesses a small Fermi surface originating from highly 2D, sharp and linearly dispersing bands (the Y-states) around the (0,$\pi$/a)-point in $k$-space. The ARPES Fermi surface agrees perfectly with that from bulk-sensitive Shubnikov de Haas data from the same crystals, proving the Y$-$states to be responsible for electrical conductivity in SrMnSb$_2$. DFT and tight binding (TB) methods are used to model the electronic states, and both show good agreement with the ARPES data. Despite the great promise of the latter, both theory approaches show the Y-states to be gapped above E$_F$, suggesting trivial topology. Subsequent analysis within both theory approaches shows the Berry phase to be zero, indicating the non-topological character of the transport in SrMnSb$_2$, a conclusion backed up by the analysis of the quantum oscillation data from our crystals.Comment: 26 pages, 10 figures, revised submission to SciPost after including changes requested by referees. All referee reports are open and can be viewed here: https://scipost.org/submissions/1711.07165v2

Coronal Temperature Diagnostic Capability of the Hinode/X-Ray Telescope Based on Self-Consistent Calibration

The X-Ray Telescope (XRT) onboard the Hinode satellite is an X-ray imager that observes the solar corona with unprecedentedly high angular resolution (consistent with its 1" pixel size). XRT has nine X-ray analysis filters with different temperature responses. One of the most significant scientific features of this telescope is its capability of diagnosing coronal temperatures from less than 1 MK to more than 10 MK, which has never been accomplished before. To make full use of this capability, accurate calibration of the coronal temperature response of XRT is indispensable and is presented in this article. The effect of on-orbit contamination is also taken into account in the calibration. On the basis of our calibration results, we review the coronal-temperature-diagnostic capability of XRT

Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages.

Activation of liver X receptors (LXRs) with synthetic agonists promotes reverse cholesterol transport and protects against atherosclerosis in mouse models. Most synthetic LXR agonists also cause marked hypertriglyceridemia by inducing the expression of sterol regulatory element-binding protein (SREBP)1c and downstream genes that drive fatty acid biosynthesis. Recent studies demonstrated that desmosterol, an intermediate in the cholesterol biosynthetic pathway that suppresses SREBP processing by binding to SCAP, also binds and activates LXRs and is the most abundant LXR ligand in macrophage foam cells. Here we explore the potential of increasing endogenous desmosterol production or mimicking its activity as a means of inducing LXR activity while simultaneously suppressing SREBP1c-induced hypertriglyceridemia. Unexpectedly, while desmosterol strongly activated LXR target genes and suppressed SREBP pathways in mouse and human macrophages, it had almost no activity in mouse or human hepatocytes in vitro. We further demonstrate that sterol-based selective modulators of LXRs have biochemical and transcriptional properties predicted of desmosterol mimetics and selectively regulate LXR function in macrophages in vitro and in vivo. These studies thereby reveal cell-specific discrimination of endogenous and synthetic regulators of LXRs and SREBPs, providing a molecular basis for dissociation of LXR functions in macrophages from those in the liver that lead to hypertriglyceridemia

Coexisting Charge-Ordered States with Distinct Driving Mechanisms in Monolayer VSe₂

Thinning crystalline materials to two dimensions (2D) creates a rich playground for electronic phases, including charge, spin, superconducting, and topological order. Bulk materials hosting charge density waves (CDWs), when reduced to ultrathin films, have shown CDW enhancement and tunability. However, charge order confined to only 2D remains elusive. Here we report a distinct charge ordered state emerging in the monolayer limit of 1T-VSe2. Systematic scanning tunneling microscopy experiments reveal that bilayer VSe2 largely retains the bulk electronic structure, hosting a tridirectional CDW. However, monolayer VSe2 -consistently across distinct substrates-exhibits a dimensional crossover, hosting two CDWs with distinct wavelengths and transition temperatures. Electronic structure calculations reveal that while one CDW is bulk-like and arises from the well-known Peierls mechanism, the other is decidedly unconventional. The observed CDW-lattice decoupling and the emergence of a flat band suggest that the second CDW could arise from enhanced electron-electron interactions in the 2D limit. These findings establish monolayer-VSe2 as a host of coexisting charge orders with distinct origins, and enable the tailoring of electronic phenomena via emergent interactions in 2D materials

Venous thromboembolism research priorities: A scientific statement from the American Heart Association and the International Society on Thrombosis and Haemostasis

Venous thromboembolism (VTE) is a major cause of morbidity and mortality. The impact of the Surgeon General’s Call to Action in 2008 has been lower than expected given the public health impact of this disease. This scientific statement highlights future research priorities in VTE, developed by experts and a crowdsourcing survey across 16 scientific organizations. At the fundamental research level (T0), researchers need to identify pathobiologic causative mechanisms for the 50% of patients with unprovoked VTE and better understand mechanisms that differentiate hemostasis from thrombosis. At the human level (T1), new methods for diagnosing, treating, and preventing VTE will allow tailoring of diagnostic and therapeutic approaches to individuals. At the patient level (T2), research efforts are required to understand how foundational evidence impacts care of patients (eg, biomarkers). New treatments, such as catheter‐based therapies, require further testing to identify which patients are most likely to experience benefit. At the practice level (T3), translating evidence into practice remains challenging. Areas of overuse and underuse will require evidence‐based tools to improve care delivery. At the community and population level (T4), public awareness campaigns need thorough impact assessment. Large population‐based cohort studies can elucidate the biologic and environmental underpinings of VTE and its complications. To achieve these goals, funding agencies and training programs must support a new generation of scientists and clinicians who work in multidisciplinary teams to solve the pressing public health problem of VTE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156163/2/rth212373_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156163/1/rth212373.pd

An Analysis of Preference Weights and Setting Priorities by Irrigation Advisory Services Users Based on the Analytic Hierarchy Process

Objective: Stakeholders-farmers from four different European areas (Campania (IT), Kujawsko-Pomorskie (PL), Limburg (NL), Andalusia (ES))-are asked to share, from the OPERA project, their opinions on five criteria that all aim at improving the use of irrigation advisory services (IASs). Each criterion has different characteristics that affect the way farmers rank it. The present study has two objectives. The first is to individuate the priorities of the preferences expressed by the stakeholders. The second objective is to carry out a ranking of the weights of the criteria by case study, ranking the groups and their associated properties among farmers' profiles. Methods: The answers to 120 questionnaires dispensed to the future users of IASs in the four agricultural sites were analyzed in detail, and then the given priorities were evaluated through the analytic hierarchy process (AHP). The AHP methodology was used to determine the relative weights of the five assessment criteria, and finally, to select the one with major value. Results and conclusions: The results show that A5 (assuring economic sustainability) was the most important criterion. The contributions provided by this study are twofold: Firstly, it presents an application of a methodology that involves the conversion of a linguistic judgement of farmers in a correspondence weight. Secondly, it tackles decision making regarding improving the use of IASs, evaluating the preferences expressed by the stakeholders. Irrigation advisory services can play a key role in assisting users to adopt new techniques and technologies for more efficient water use and increased production