Pinyon and Juniper Encroachment into Sagebrush Ecosystems Impacts Distribution and Survival of Greater Sage-Grouse

AbstractIn sagebrush (Artemisia spp.) ecosystems, encroachment of pinyon (Pinus spp.) and juniper (Juniperus spp.; hereafter, “pinyon-juniper”) trees has increased dramatically since European settlement. Understanding the impacts of this encroachment on behavioral decisions, distributions, and population dynamics of greater sage-grouse (Centrocercus urophasianus) and other sagebrush obligate species could help benefit sagebrush ecosystem management actions. We employed a novel two-stage Bayesian model that linked avoidance across different levels of pinyon-juniper cover to sage-grouse survival. Our analysis relied on extensive telemetry data collected across 6 yr and seven subpopulations within the Bi-State Distinct Population Segment (DPS), on the border of Nevada and California. The first model stage indicated avoidance behavior for all canopy cover classes on average, but individual grouse exhibited a high degree of heterogeneity in avoidance behavior of the lowest cover class (e.g., scattered isolated trees). The second stage modeled survival as a function of estimated avoidance parameters and indicated increased survival rates for individuals that exhibited avoidance of the lowest cover class. A post hoc frailty analysis revealed the greatest increase in hazard (i.e., mortality risk) occurred in areas with scattered isolated trees consisting of relatively high primary plant productivity. Collectively, these results provide clear evidence that local sage-grouse distributions and demographic rates are influenced by pinyon-juniper, especially in habitats with higher primary productivity but relatively low and seemingly benign tree cover. Such areas may function as ecological traps that convey attractive resources but adversely affect population vital rates. To increase sage-grouse survival, our model predictions support reducing actual pinyon-juniper cover as low as 1.5%, which is lower than the published target of 4.0%. These results may represent effects of pinyon-juniper cover in areas with similar ecological conditions to those of the Bi-State DPS, where populations occur at relatively high elevations and pinyon-juniper is abundant and widespread

Perforin enhances the granulysin-induced lysis of Listeria innocua in human dendritic cells

Background: Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells play an essential role in the host defence against intracellular pathogens such as Listeria, and Mycobacteria. The key mediator of bacteria-directed cytotoxicity is granulysin, a 9 kDa protein stored in cytolytic granules together with perforin and granzymes. Granulysin binds to cell membranes and is subsequently taken up via a lipid raft-associated mechanism. In dendritic cells (DC) granulysin is further transferred via early endosomes to L. innocua-containing phagosomes were bacteriolysis is induced. In the present study we analysed the role of perforin in granulysin-induced intracellular bacteriolysis in DC. Results: We found granulysin-induced lysis of intracellular Listeria significantly increased when perforin was simultaneously present. In pulse-chase experiments enhanced bacteriolysis was observed when perforin was added up to 25 minutes after loading the cells with granulysin demonstrating no ultimate need for simultaneous uptake of granulysin and perforin. The perforin concentration sufficient to enhance granulysin-induced intracellular bacteriolysis did not cause permanent membrane pores in Listeria-challenged DC as shown by dye exclusion test and LDH release. This was in contrast to non challenged DC that were more susceptible to perforin lysis. For Listeria-challenged DC, there was clear evidence for an Ca2+ influx in response to sublytic perforin demonstrating a short-lived change in the plasma membrane permeability. Perforin treatment did not affect granulysin binding, initial uptake or intracellular trafficking to early endosomes. However, enhanced colocalization of granulysin with listerial DNA in presence of perforin was found by confocal laser scanning microscopy. Conclusion: The results provide evidence that perforin increases granulysin-mediated killing of intracellular Listeria by enhanced phagosome-endosome fusion triggered by a transient Ca2+ flux

FCET2EC (From controlled experimental trial to = 2 everyday communication): How effective is intensive integrative therapy for stroke-induced chronic aphasia under routine clinical conditions? A study protocol for a randomized controlled trial

Background: Therapy guidelines recommend speech and language therapy (SLT) as the “gold standard” for aphasia treatment. Treatment intensity (i.e., ≥5 hours of SLT per week) is a key predictor of SLT outcome. The scientific evidence to support the efficacy of SLT is unsatisfactory to date given the lack of randomized controlled trials (RCT), particularly with respect to chronic aphasia (lasting for >6 months after initial stroke). This randomized waiting list-controlled multi-centre trial examines whether intensive integrative language therapy provided in routine in- and outpatient clinical settings is effective in improving everyday communication in chronic post-stroke aphasia. Methods/Design: Participants are men and women aged 18 to 70 years, at least 6 months post an ischemic or haemorrhagic stroke resulting in persisting language impairment (i.e., chronic aphasia); 220 patients will be screened for participation, with the goal of including at least 126 patients during the 26-month recruitment period. Basic language production and comprehension abilities need to be preserved (as assessed by the Aachen Aphasia Test).Therapy consists of language-systematic and communicative-pragmatic exercises for at least 2 hours/day and at least 10 hours/week, plus at least 1 hour self-administered training per day, for at least three weeks. Contents of therapy are adapted to patients’ individual impairment profiles.Prior to and immediately following the therapy/waiting period, patients’ individual language abilities are assessed via primary and secondary outcome measures. The primary (blinded) outcome measure is the A-scale (informational content, or 'understandability’, of the message) of the Amsterdam-Nijmegen Everyday Language Test (ANELT), a standardized measure of functional communication ability. Secondary (unblinded) outcome measures are language-systematic and communicative-pragmatic language screenings and questionnaires assessing life quality as viewed by the patient as well as a relative.The primary analysis tests for differences between the therapy group and an untreated (waiting list) control group with respect to pre- versus post 3-week-therapy (or waiting period, respectively) scores on the ANELT A-scale. Statistical between-group comparisons of primary and secondary outcome measures will be conducted in intention-to-treat analyses. Long-term stability of treatment effects will be assessed six months post intensive SLT (primary and secondary endpoints)

The sodium iodide symporter (NIS) as theranostic gene: its emerging role in new imaging modalities and non-viral gene therapy

Cloning of the sodium iodide symporter (NIS) in 1996 has provided an opportunity to use NIS as a powerful theranostic transgene. Novel gene therapy strategies rely on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of therapeutic radionuclides. This review highlights the remarkable progress during the last two decades in the development of the NIS gene therapy concept using selective non-viral gene delivery vehicles including synthetic polyplexes and genetically engineered mesenchymal stem cells. In addition, NIS is a sensitive reporter gene and can be monitored by high resolution PET imaging using the radiotracers sodium [ 124 I]iodide ([ 124 I]NaI) or [ 18 F]tetrafluoroborate ([ 18 F]TFB). We performed a small preclinical PET imaging study comparing sodium [ 124 I]iodide and in-house synthesized [ 18 F]TFB in an orthotopic NIS-expressing glioblastoma model. The results demonstrated an improved image quality using [ 18 F]TFB. Building upon these results, we will be able to expand the NIS gene therapy approach using non-viral gene delivery vehicles to target orthotopic tumor models with low volume disease, such as glioblastoma

Effective decrease of photoelectric emission threshold from gold plated surfaces

Many applications require charge neutralisation of isolated test bodies and this has been successfully done using photoelectric emission from surfaces which are electrically benign(gold) or superconducting (niobium). Gold surfaces nominally have a high work function ($\sim 5.1$\,eV)which should require deep UV photons for photoemission. In practice it has been found that it can be achieved with somewhat lower energy photons with indicative work functions of ($4.1-4.3$\,eV). A detailed working understanding of the process is lacking and this work reports on a study of the photoelectric emission properties of 4.6x4.6 cm^2 gold plated surfaces, representative of those used in typical satellite applications with a film thickness of 800 nm, and measured surface roughnesses between 7 and 340 nm. Various UV sources with photon energies from 4.8 to 6.2 eV and power outputs from 1 nW to 1000 nW, illuminated a ~0.3 cm^2 of the central surface region at angles of incidence from 0 to 60 degrees. Final extrinsic quantum yields in the range 10 ppm to 44 ppm were reliably obtained during 8 campaigns, covering a ~3 year period, but with intermediate long-term variations lasting several weeks and, in some cases, bake-out procedures at up to 200 C. Experimental results were obtained in a vacuum system with a baseline pressure of ~10^{-7} mbar at room temperature. A working model, designed to allow accurate simulation of any experimental configuration, is proposed.Comment: 35 pages, 12 figure

Measurement of the directional sensitivity of Dark Matter Time Projection Chamber detectors

The Dark Matter Time Projection Chamber (DMTPC) is a direction-sensitive detector designed to measure the direction of recoiling $^{19}$F and $^{12}$C nuclei in low-pressure CF$_4$ gas using optical and charge readout systems. In this paper, we employ measurements from two DMTPC detectors, with operating pressures of 30-60 torr, to develop and validate a model of the directional response and performance of such detectors as a function of recoil energy. Using our model as a benchmark, we formulate the necessary specifications for a scalable directional detector with sensitivity comparable to that of current-generation counting (non-directional) experiments, which measure only recoil energy. Assuming the performance of existing DMTPC detectors, as well as current limits on the spin-dependent WIMP-nucleus cross section, we find that a 10-20 kg scale direction-sensitive detector is capable of correlating the measured direction of nuclear recoils with the predicted direction of incident dark matter particles and providing decisive (3$\sigma$) confirmation that a candidate signal from a non-directional experiment was indeed induced by elastic scattering of dark matter particles off of target nuclei.Comment: 13 pages, 10 figures. Accepted for publication in Phys. Rev. D. Added color figures, switched to more compact layout, and fixed some reference

Efficacy and Safety of Antioxidant Treatment With α-Lipoic Acid Over 4 Years in Diabetic Polyneuropathy

Objective: To evaluate the efficacy and safety of α-lipoic acid (ALA) over 4 years in mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy (DSPN). Research Design and Methods: In a multicenter randomized double-blind parallel-group trial, 460 diabetic patients with mild-to-moderate DSPN were randomly assigned to oral treatment with 600 mg ALA once daily (n = 233) or placebo (n = 227) for 4 years. Primary end point was a composite score (Neuropathy Impairment Score [NIS]–Lower Limbs [NIS-LL] and seven neurophysiologic tests). Secondary outcome measures included NIS, NIS-LL, nerve conduction, and quantitative sensory tests (QSTs). Results: Change in primary end point from baseline to 4 years showed no significant difference between treatment groups (P = 0.105). Change from baseline was significantly better with ALA than placebo for NIS (P = 0.028), NIS-LL (P = 0.05), and NIS-LL muscular weakness subscore (P = 0.045). More patients showed a clinically meaningful improvement and fewer showed progression of NIS (P = 0.013) and NIS-LL (P = 0.025) with ALA than with placebo. Nerve conduction and QST results did not significantly worsen with placebo. Global assessment of treatment tolerability and discontinuations due to lack of tolerability did not differ between the groups. The rates of serious adverse events were higher on ALA (38.1%) than on placebo (28.0%). Conclusions: Four-year treatment with ALA in mild-to-moderate DSPN did not influence the primary composite end point but resulted in a clinically meaningful improvement and prevention of progression of neuropathic impairments and was well tolerated. Because the primary composite end point did not deteriorate significantly in placebo-treated subjects, secondary prevention of its progression by ALA according to the trial design was not feasible