Effect-specific analysis of propagation parameters

Results of propagation measurements with the satellite OLYMPUS carried out at 12.5, 20, and 30 GHz at the Research Center of the Deutsche Bundespost Telekom are discussed. In particular, attenuation, scintillation, and depolarization measurements are analyzed with special emphasis on frequency scaling of the various effects

The Beginning, the Middle, and the End: New Tools for the Scholarly Edition

This article addresses the design of a dynamic repository interface to support numerous scholarly activities. Starting with the four fundamental functions associated with persistent storage — create, read, update, and delete (CRUD) — we tested, as an organizing rubric for the interface, the acronym CREAM: Create (represent, illustrate); Read (sample, read); Enhance (refer, annotate, process); Analyze (search, select, visualize, mine, cluster); and Manage (track, label, transform). Based on a card-sorting exercise conducted with researchers, we conclude that a slightly modified rubric of CREAMS offers a useful starting point that emphasizes the enriched functionality a scholarly repository or similarly complex digital environment requires, as well as the immense challenge of designing conceptually clear interfaces, even for a relatively homogenous community of researchers

Bladder cancer cells acquire competent mechanisms to escape Fas-mediated apoptosis and immune surveillance in the course of malignant transformation

Mechanisms of resistance against Fas-mediated cell killing have been reported in different malignancies. However, the biological response of immune escape mechanisms might depend on malignant transformation of cancer cells. In this study we investigated different mechanisms of immune escape in 2 well-differentiated low-grade (RT4 and RT112) and 2 poorly differentiated high-grade (T24 and TCCSUP) bladder cancer cell lines. Fas, the receptor of Fas-ligand, is expressed and shedded by human transitional bladder carcinoma cell lines RT4, RT112, T24 and TCCSUP. Cytotoxicity and apoptosis assays demonstrate that in spite of the Fas expression, poorly differentiated T24 and TCCSUP cells are insensitive towards either recombinant Fas-ligand or agonistic apoptosis-inducing monoclonal antibody against Fas. In poorly differentiated T24 and TCCSUP cell lines we were able to detect marked Fas-ligand protein by flow cytometry and Western blot analysis. In grade 1 RT4 and RT112 cells only minor expression of Fas-ligand possibly because of proteinase action. Fas-ligand mRNA translation or post-translational processing seems to be regulated differentially in the cancer cell lines depending on malignant transformation. In co-culture experiments we show that poorly differentiated cells can induce apoptosis and cell death in Jurkat cells and activated peripheral blood mononuclear cells. This in vitro study suggests that bladder cancer cells can take advantage of different mechanisms of immune evasion and become more competent in avoiding immune surveillance during transformation to higher-grade malignant disease. © 2001 Cancer Research Campaign www.bjcancer.co

Biomass burning fuel consumption rates: a field measurement database

Landscape fires show large variability in the amount of biomass or fuel consumed per unit area burned. Fuel consumption (FC) depends on the biomass available to burn and the fraction of the biomass that is actually combusted, and can be combined with estimates of area burned to assess emissions. While burned area can be detected from space and estimates are becoming more reliable due to improved algorithms and sensors, FC is usually modeled or taken selectively from the literature. We compiled the peerreviewed literature on FC for various biomes and fuel categories to understand FC and its variability better, and to provide a database that can be used to constrain biogeochemical models with fire modules. We compiled in total 77 studies covering 11 biomes including savanna (15 studies, average FC of 4.6 t DM (dry matter) ha 1 with a standard deviation of 2.2),tropical forest (n = 19, FC = 126 +/- 77),temperate forest (n = 12, FC = 58 +/- 72),boreal forest (n = 16, FC = 35 +/- 24),pasture (n = 4, FC = 28 +/- 9.3),shifting cultivation (n = 2, FC = 23, with a range of 4.0-43),crop residue (n = 4, FC = 6.5 +/- 9.0),chaparral (n = 3, FC = 27 +/- 19),tropical peatland (n = 4, FC = 314 +/- 196),boreal peatland (n = 2, FC = 42 [42-43]),and tundra (n = 1, FC = 40). Within biomes the regional variability in the number of measurements was sometimes large, with e. g. only three measurement locations in boreal Russia and 35 sites in North America. Substantial regional differences in FC were found within the defined biomes: for example, FC of temperate pine forests in the USA was 37% lower than Australian forests dominated by eucalypt trees. Besides showing the differences between biomes, FC estimates were also grouped into different fuel classes. Our results highlight the large variability in FC, not only between biomes but also within biomes and fuel classes. This implies that substantial uncertainties are associated with using biome-averaged values to represent FC for whole biomes. Comparing the compiled FC values with co-located Global Fire Emissions Database version 3 (GFED3) FC indicates that modeling studies that aim to represent variability in FC also within biomes, still require improvements as they have difficulty in representing the dynamics governing FC

Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum

The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na+ regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na+ homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na+ homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes

Tutoring Multilingual Students: Shattering the Myths

This is the author's accepted manuscript, made available 18 months after publication with the permission of the publisher.The increasing linguistic and cultural diversification of North America has resulted in large numbers of multilingual students attending college and university and seeking curricular and extracurricular support with reading and writing (Ruecker, 2011; Teranishi, C. Suárez-Orozco, & M. Suárez-Orozco, 2011). In the past, learning and writing centers hired “ESL specialists” to provide support. But this model, given the ubiquity of multilingual students in higher education today, is no longer sustainable. Instead, all tutors must learn the skills necessary to support the academic literacy development of these writers, and that means that the way tutors are trained must change. Because the lived reality of the majority of tutors (and center administrators) is monolingual (Bailey, 2012; Barron & Grimm, 2002), examining the myths generally held about multilingual students is essential to both our development as tutors and the development of our students as academic readers and writers of English. Only after raising critical awareness about these “misguided ideas” will training specific to tutoring multilingual students make sense and be put into practice (Gillespie & Lerner, 2008, p. 117). In this article, I present and challenge myths about multilingual writers and myths about how to tutor them

Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling.

BACKGROUND: Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented. METHOD AND FINDINGS: The properties of ACT-451840 are described, including its spectrum of activities against multiple life cycle stages of the human malaria parasite Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well as oral in vivo efficacies in two murine malaria models that permit infection with the human and the rodent parasites P. falciparum and Plasmodium berghei, respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7 mg/kg against P. falciparum (95% confidence interval: 3.3-4.9 mg/kg) and 13 mg/kg against P. berghei (95% confidence interval: 11-16 mg/kg). ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23-39). The compound's preclinical safety profile is presented and is in line with the published results of the first-in-man study in healthy male participants, in whom ACT-451840 was well tolerated. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in the murine models (defined either as antimalarial activity or as survival) in relation to area under the concentration versus time curve (AUC), maximum observed plasma concentration (Cmax), and time above a threshold concentration. The determination of the dose-efficacy relationship of ACT-451840 under curative conditions in rodent malaria models allowed prediction of the human efficacious exposure. CONCLUSION: The dual activity of ACT-451840 against asexual and sexual stages of P. falciparum and the activity on P. vivax have the potential to meet the specific profile of a target compound that could replace the fast-acting artemisinin component and harbor additional gametocytocidal activity and, thereby, transmission-blocking properties. The fast parasite reduction ratio (PRR) and gametocytocidal effect of ACT-451840 were recently also confirmed in a clinical proof-of-concept (POC) study

3066 consecutive Gamma Nails. 12 years experience at a single centre

<p>Abstract</p> <p>Background</p> <p>Fixation of trochanteric hip fractures using the Gamma Nail has been performed since 1988 and is today well established and wide-spread. However, a number of reports have raised serious concerns about the implant's complication rate. The main focus has been the increased risk of a subsequent femoral shaft fracture and some authors have argued against its use despite other obvious advantages, when this implant is employed.</p> <p>Through access to a uniquely large patient data base available, which is available for analysis of trochanteric fractures; we have been able to evaluate the performance of the Gamma Nail over a twelve year period.</p> <p>Methods</p> <p>3066 consecutive patients were treated for trochanteric fractures using Gamma Nails between 1990 and 2002 at the Centre de Traumatologie et de l'Orthopedie (CTO), Strasbourg, France. These patients were retrospectively analysed. Information on epidemiological data, intra- and postoperative complications and patients' outcome was retrieved from patient notes. All available radiographs were assessed by a single reviewer (AJB).</p> <p>Results</p> <p>The results showed a low complication rate with the use of the Gamma Nail. There were 137 (4.5%) intraoperative fracture-related complications. Moreover 189 (6.2%) complications were detected postoperatively and during follow-up. Cut-out of the lag screw from the femoral head was the most frequent mechanical complication (57 patients, 1.85%), whereas a postoperative femoral shaft fracture occurred in 19 patients (0.6%). Other complications, such as infection, delayed healing/non-union, avascular femoral head necrosis and distal locking problems occurred in 113 patients (3.7%).</p> <p>Conclusions</p> <p>The use of the Gamma Nail in trochanteric hip fractures is a safe method with a low complication rate. In particular, a low rate of femoral shaft fractures was reported. The low complication rate reported in this series can probably be explained by strict adherence to a proper surgical technique.</p

Mechanisms of the noxious inflammatory cycle in cystic fibrosis

Multiple evidences indicate that inflammation is an event occurring prior to infection in patients with cystic fibrosis. The self-perpetuating inflammatory cycle may play a pathogenic part in this disease. The role of the NF-κB pathway in enhanced production of inflammatory mediators is well documented. The pathophysiologic mechanisms through which the intrinsic inflammatory response develops remain unclear. The unfolded mutated protein cystic fibrosis transmembrane conductance regulator (CFTRΔF508), accounting for this pathology, is retained in the endoplasmic reticulum (ER), induces a stress, and modifies calcium homeostasis. Furthermore, CFTR is implicated in the transport of glutathione, the major antioxidant element in cells. CFTR mutations can alter redox homeostasis and induce an oxidative stress. The disturbance of the redox balance may evoke NF-κB activation and, in addition, promote apoptosis. In this review, we examine the hypotheses of the integrated pathogenic processes leading to the intrinsic inflammatory response in cystic fibrosis