Improving interinstitutional and intertechnology consistency of pulmonary SBRT by dose prescription to the mean internal target volume dose.

PURPOSE: Dose, fractionation, normalization and the dose profile inside the target volume vary substantially in pulmonary stereotactic body radiotherapy (SBRT) between different institutions and SBRT technologies. Published planning studies have shown large variations of the mean dose in planning target volume (PTV) and gross tumor volume (GTV) or internal target volume (ITV) when dose prescription is performed to the PTV covering isodose. This planning study investigated whether dose prescription to the mean dose of the ITV improves consistency in pulmonary SBRT dose distributions. MATERIALS AND METHODS: This was a multi-institutional planning study by the German Society of Radiation Oncology (DEGRO) working group Radiosurgery and Stereotactic Radiotherapy. CT images and structures of ITV, PTV and all relevant organs at risk (OAR) for two patients with early stage non-small cell lung cancer (NSCLC) were distributed to all participating institutions. Each institute created a treatment plan with the technique commonly used in the institute for lung SBRT. The specified dose fractionation was 3â€¯× 21.5 Gy normalized to the mean ITV dose. Additional dose objectives for target volumes and OAR were provided. RESULTS: In all, 52 plans from 25 institutions were included in this analysis: 8 robotic radiosurgery (RRS), 34 intensity-modulated (MOD), and 10 3D-conformal (3D) radiation therapy plans. The distribution of the mean dose in the PTV did not differ significantly between the two patients (median 56.9 Gy vs 56.6 Gy). There was only a small difference between the techniques, with RRS having the lowest mean PTV dose with a median of 55.9 Gy followed by MOD plans with 56.7 Gy and 3D plans with 57.4 Gy having the highest. For the different organs at risk no significant difference between the techniques could be found. CONCLUSIONS: This planning study pointed out that multiparameter dose prescription including normalization on the mean ITV dose in combination with detailed objectives for the PTV and ITV achieve consistent dose distributions for peripheral lung tumors in combination with an ITV concept between different delivery techniques and across institutions.

Hospital-based enhanced surveillance for West Nile virus neuroinvasive disease.

Accurate data on the incidence of West Nile virus (WNV) disease are important for directing public health education and control activities. The objective of this project was to assess the underdiagnosis of WNV neuroinvasive disease through laboratory testing of patients with suspected viral meningitis or encephalitis at selected hospitals serving WNV-endemic regions in three states. Of the 279 patients with cerebrospinal fluid (CSF) specimens tested for WNV immunoglobulin M (IgM) antibodies, 258 (92%) were negative, 19 (7%) were positive, and two (1%) had equivocal results. Overall, 63% (12/19) of patients with WNV IgM-positive CSF had WNV IgM testing ordered by their attending physician. Seven (37%) cases would not have been identified as probable WNV infections without the further testing conducted through this project. These findings indicate that over a third of WNV infections in patients with clinically compatible neurological illness might be undiagnosed due to either lack of testing or inappropriate testing, leading to substantial underestimates of WNV neuroinvasive disease burden. Efforts should be made to educate healthcare providers and laboratorians about the local epidemiology of arboviral diseases and the optimal tests to be used in different clinical situations.

Ion thrusters for electric propulsion: Scientific issues developing a niche technology into a game changer.

The transition from old space to new space along with increasing commercialization has a major impact on space flight, in general, and on electric propulsion (EP) by ion thrusters, in particular. Ion thrusters are nowadays used as primary propulsion systems in space. This article describes how these changes related to new space affect various aspects that are important for the development of EP systems. Starting with a historical overview of the development of space flight and of the technology of EP systems, a number of important missions with EP and the underlying technologies are presented. The focus of our discussion is the technology of the radio frequency ion thruster as a prominent member of the gridded ion engine family. Based on this discussion, we give an overview of important research topics such as the search for alternative propellants, the development of reliable neutralizer concepts based on novel insert materials, as well as promising neutralizer-free propulsion concepts. In addition, aspects of thruster modeling and requirements for test facilities are discussed. Furthermore, we address aspects of space electronics with regard to the development of highly efficient electronic components as well as aspects of electromagnetic compatibility and radiation hardness. This article concludes with a presentation of the interaction of EP systems with the spacecraft.

Importance of the biofilm matrix for the erosion stability of Bacillus subtilis NCIB 3610 biofilms.

Production and secretion of biomolecules can provide new emergent functionalities to the synthesizing organism. In particular, the secretion of extracellular polymeric substances (EPS) by biofilm forming bacteria creates a biofilm matrix that protects the individual bacteria within the biofilm from external stressors such as antibiotics, chemicals and shear flow. Although the main matrix components of biofilms formed by Bacillus subtilis are known, it remains unclear how these matrix components contribute to the erosion stability of B. subtilis biofilms. Here, we combine different biophysical techniques to assess this relation. In particular, we quantify the importance of specific biofilm matrix components on the erosion behavior of biofilms formed by the well-studied Bacillus subtilis NCIB 3610. We find that the absence of biofilm matrix components decreases the erosion stability of NCIB 3610 biofilms in water, largely by abolishing the hydrophobic surface properties of the biofilm and by reducing the biofilm stiffness. However, the erosion resistance of NCIB 3610 biofilms is strongly increased in the presence of metal ions or the antibiotic ciprofloxacin. In the first case, unspecific ionic cross-linking of biofilm components or individual bacteria seems to be responsible for the observed effect, and in the second case there seems to be an unspecific interaction between the antibiotic and the biofilm matrix. Taken together, our results emphasize the importance of the biofilm matrix to reduce biofilm erosion and give insights into how the specific biomolecules interact with certain chemicals to fulfill this task.

fcc-bcc phase transition in plasma crystals using time-resolved measurements.

Three-dimensional plasma crystals are often described as Yukawa systems for which a phase transition between the crystal structures fcc and bcc has been predicted. However, experimental investigations of this transition are missing. We use a fast scanning video camera to record the crystallization process of 70 000 microparticles and investigate the existence of the fcc-bcc phase transition at neutral gas pressures of 30, 40, and 50 Pa. To analyze the crystal, robust phase diagrams with the help of a machine learning algorithm are calculated. This work shows that the phase transition can be investigated experimentally and makes a comparison with numerical results of Yukawa systems. The phase transition is analyzed in dependence on the screening parameter and structural order. We suggest that the transition is an effect of gravitational compression of the plasma crystal. Experimental investigations of the fcc-bcc phase transition will provide an opportunity to estimate the coupling strength Γ by comparison with numerical results of Yukawa systems.

ARCTIC CHANGE AND POSSIBLE INFLUENCE ON MID-LATITUDE CLIMATE AND WEATHER: A US CLIVAR White Paper.

The Arctic has warmed more than twice as fast as the global average since the mid 20th century, a phenomenon known as Arctic amplification (AA). These profound changes to the Arctic system have coincided with a period of ostensibly more frequent events of extreme weather across the Northern Hemisphere (NH) mid-latitudes, including extreme heat and rainfall events and recent severe winters. Though winter temperatures have generally warmed since 1960 over mid-to-high latitudes, the acceleration in the rate of warming at high-latitudes, relative to the rest of the NH, started approximately in 1990. Trends since 1990 show cooling over the NH continents, especially in Northern Eurasia. The possible link between Arctic change and mid-latitude climate and weather has spurred a rush of new observational and modeling studies. A number of workshops held during 2013-2014 have helped frame the problem and have called for continuing and enhancing efforts for improving our understanding of Arctic-mid-latitude linkages and its attribution to the occurrence of extreme climate and weather events. Although these workshops have outlined some of the major challenges and provided broad recommendations, further efforts are needed to synthesize the diversified research results to identify where community consensus and gaps exist. Building upon findings and recommendations of the previous workshops, the US CLIVAR Working Group on Arctic Change and Possible Influence on Mid-latitude Climate and Weather convened an international workshop at Georgetown University in Washington, DC, on February 1-3, 2017. Experts in the fields of atmosphere, ocean, and cryosphere sciences assembled to assess the rapidly evolving state of understanding, identify consensus on knowledge and gaps in research, and develop specific actions to accelerate progress within the research community. With more than 100 participants, the workshop was the largest and most comprehensive gathering of climate scientists to address the topic to date. In this white paper, we synthesize and discuss outcomes from this workshop and activities involving many of the working group members. WORKSHOP FINDINGS: Rapid Arctic change - Emergence of new forcing (external and internal) of atmospheric circulation: Rapid Arctic change is evident in the observations and is simulated and projected by global climate models. AA has been attributed to sea ice and snow decline (regionally and seasonally varying). However this cannot explain why AA is greatest in winter and weakest in summer. It was argued at the workshop that other factors can also greatly contribute to AA including: increased downwelling longwave radiation from greenhouse gases (including greater water vapor concentrations from local and remote sources); increasing ocean heat content, due to local and remote processes; regional and hemispheric atmospheric circulation changes; increased poleward heat transport in the atmosphere and ocean; and cloud radiative forcing. In particular, there is emerging observational evidence that an enhanced poleward transport of sensible and latent heat plays a very important role in the AA of the recent decades, and that this enhancement is mostly fueled by changes in the atmospheric circulation. We concluded that our understanding of AA is incomplete, especially the relative contributions from the different radiative, thermodynamic, and dynamic processes.Arctic mid-latitude linkages - Focusing on seasonal and regional linkages and addressing sources of inconsistency and uncertainty among studies: The topic of Arctic mid-latitude linkages is controversial and was vigorously debated at the workshop. However, we concluded that rapid Arctic change is contributing to changes in mid-latitude climate and weather, as well as the occurrence of extreme events. But how significant the contribution is and what mechanisms are responsible are less well understood. Based on the synthesis efforts of observational and modeling studies, we identified a list of proposed physical processes or mechanisms that may play important roles in linking Arctic change to mid-latitude climate and weather. The list, ordered from high to low confidence, includes: increasing geopotential thickness over the polar cap; weakening of the thermal wind; modulating stratosphere-troposphere coupling; exciting anomalous planetary waves or stationary Rossby wave trains in winter and modulating transient synoptic waves in summer; altering storm tracks and behavior of blockings; and increasing frequency of occurrence of summer wave resonance. The pathway considered most robust is the propagation of planetary/Rossby waves excited by the diminished Barents-Kara sea ice, contributing to a northwestward expansion and intensification of the Siberian high leading to cold Eurasian winters. OPPORTUNITIES AND RECOMMENDATIONS: An important goal of the workshop was achieved: to hasten progress towards consensus understanding and identification of knowledge gaps. Based on the workshop findings, we identify specific opportunities to utilize observations and models, particularly a combination of them, to enable and accelerate progress in determining the mechanisms of rapid Arctic change and its mid-latitude linkages.Observations: Due to the remoteness and harsh environmental conditions of the Arctic, in situ observational time series are highly limited spatially and temporally in the region.Six recommendations to expand approaches using observational datasets and analyses of Arctic change and mid-latitude linkages include: Synthesize new Arctic observations;Create physically-based sea ice-ocean surface forcing datasets;Systematically employ proven and new metrics;Analyze paleoclimate data and new longer observational datasets;Utilize new observational analysis methods that extend beyond correlative relationships; andConsider both established and new theories of atmospheric and oceanic dynamics to interpret and guide observational and modeling studies.Model experiments: We acknowledge that models provide the primary tool for gaining a mechanistic understanding of variability and change in the Arctic and at mid-latitudes. Coordinated modeling studies should include approaches using a hierarchy of models from conceptual, simple component, or coupled models to complex atmospheric climate models or fully coupled Earth system models. We further recommend to force dynamical models with consistent boundary forcings.Three recommendations to advance modeling and synthesis understanding of Arctic change and mid-latitude linkages include: Establish a Modeling Task Force to plan protocols, forcing, and output parameters for coordinated modeling experiments (Polar Amplification Model Intercomparison Project; PAMIP);Furnish experiment datasets to the community through open access (via Earth System Grid); andPromote analysis within the community of the coordinated modeling experiments to understand mechanisms for AA and to further understand pathways for Arctic mid-latitude linkages.

Plasmakristall-4: New complex (dusty) plasma laboratory on board the International Space Station.

New complex-plasma facility, Plasmakristall-4 (PK-4), has been recently commissioned on board the International Space Station. In complex plasmas, the subsystem of µm-sized microparticles immersed in low-pressure weakly ionized gas-discharge plasmas becomes strongly coupled due to the high (103-104 e) electric charge on the microparticle surface. The microparticle subsystem of complex plasmas is available for the observation at the kinetic level, which makes complex plasmas appropriate for particle-resolved modeling of classical condensed matter phenomena. The main purpose of PK-4 is the investigation of flowing complex plasmas. To generate plasma, PK-4 makes use of a classical dc discharge in a glass tube, whose polarity can be switched with the frequency of the order of 100 Hz. This frequency is high enough not to be felt by the relatively heavy microparticles. The duty cycle of the polarity switching can be also varied allowing to vary the drift velocity of the microparticles and (when necessary) to trap them. The facility is equipped with two videocameras and illumination laser for the microparticle imaging, kaleidoscopic plasma glow observation system and minispectrometer for plasma diagnostics and various microparticle manipulation devices (e.g., powerful manipulation laser). Scientific experiments are programmed in the form of scripts written with the help of specially developed C scripting language libraries. PK-4 is mainly operated from the ground (control center CADMOS in Toulouse, France) with the support of the space station crew. Data recorded during the experiments are later on delivered to the ground on the removable hard disk drives and distributed to participating scientists for the detailed analysis.

Force field inside the void in complex plasmas under microgravity conditions.

Observations of complex plasmas under microgravity conditions onboard the International Space Station performed with the Plasma-Kristall experiment-Nefedov facility are reported. A weak instability of the boundary between the central void (region free of microparticles) and the microparticle cloud is observed at low gas pressures. The instability leads to periodic injections of a relatively small number of particles into the void region (by analogy this effect is called the "trampoline effect"). The trajectories of injected particles are analyzed providing information on the force field inside the void. The experimental results are compared with theory which assumes that the most important forces inside the void are the electric and the ion drag forces. Good agreement is found clearly indicating that under conditions investigated the void formation is caused by the ion drag force.

Particle charge in the bulk of gas discharges.

An experimental determination of particle charge in a bulk dc discharge plasma covering a wide range of neutral gas pressures, was recently reported [S. Ratynskaia, Phys. Rev. Lett. 93, 085001 (2004)]. The charges obtained were several times smaller than the predictions of collisionless orbital motion limited theory. This discrepancy was attributed to the effect of ion-neutral collisions. In the present paper a more detailed description of this experiment is provided and additional experimental results obtained with particles of different sizes are reported. The measurements are compared with molecular dynamics simulations of particle charging for conditions similar to those of the experiment, with other available experimental data on particle charge in the bulk of gas discharges, and with a simple analytical model accounting for ion-neutral collisions. All the considered evidence indicates that ion-neutral collisions represent a very important factor, which significantly affects (reduces) the particle charge under typical discharge conditions.

Perspectives of paid whole and plasma donation.

Although payment of blood donors is rejected by the WHO, the FDA, the EU, and the Red Cross (RC), in Germany, monetary compensation of expenses is permitted not only for plasmapheresis but also for whole blood donation. The structure and organisation of the institutions ensuring the blood supply in Germany and the pertaining aspects of blood safety will be discussed. Data reported to the health authorities show that the frequency of transfusion-transmitted infection markers in the German donor population is low and that only very few infections have been transmitted through blood. This is underlined by a detailed analysis of the paid donor population of a small university blood service (UBS). The analysis documents a very stable and reliable cohort of predominantly repeat donors. Unpaid RC donors of blood units transfused to patients at the university hospital of Marburg showed a sixteen-times higher sero-conversion rate than those of the UBS (p < 0.0001). However, in a survey, 77% of the paid donors denied continuation of blood donation in the event of payment being stopped. Therefore non-remuneration would result in acute blood supply shortages. Since increased blood shortages are to be expected anyway in the near future, all measures improving the supply of safe blood, including monetary compensation, should be objectively discussed without prejudice.

Regulation of immunoglobulin production after human marrow grafting. The role of helper and suppressor T cells in acute graft-versus-host disease.

The effect of acute graft-versus host disease (GVHD) on T4 and T8 lymphocyte regulation of in vitro immunoglobulin production was explored. The peripheral blood lymphocytes from 20 patients were studied sequentially in the first 100 days after sibling bone marrow grafting for hematologic malignancy or aplastic anemia. T and non-T lymphocytes were prepared from peripheral blood by Ficoll-Hypaque density gradient centrifugation and sheep erythrocyte rosetting. T cells were enriched for T4 or T8 cells and cocultured for six days with pokeweed mitogen and autologous non-T or T and non-T cells from unrelated normal individuals. Immunoglobulin production was assessed using a reverse hemolytic plaque assay. All three patients without acute GVHD had failure of non-T cells to secrete immunoglobulin, one had failure of helper T cell activity, and 2 developed suppressor T cells. Similarly, all six patients studied sequentially after the development of GVHD had non-T-cell failure, five developed helper T cell failure, and five had suppressor T cells. These data suggest no difference in lymphocyte function before or after the development of acute GVHD. When the T cells of these patients were split into T4 and T8 subpopulations and studied for immunoglobulin production there was helper T cell failure in 4 of 9 tests with enriched T4 populations. Five of 9 tests with T8 enriched populations showed suppressor activity. Suppressor T cell function was also seen in 4 of 9 tests with with T4-enriched populations. These data show that T cell function does not necessarily correlate with the surface phenotype during the first 100 days after grafting. A role for cytomegalovirus (CMV) infection in bringing out suppressor activity is suggested, because among patients without GVHD, 6 of 8 tests in CMV-positive patients showed suppressor cells compared with none of 4 tests in patients without CMV infection.

A pocket database for cloning.

A system of programs is presented that turns the HP 48SX calculator into a pocket database for molecular biology with a library of restriction enzymes and plasmids. The operations of the calculator are extended to handle DNA and peptide sequences much like numbers. The software provides a comprehensive system for cloning and includes functions for cutting and ligation, DNA-peptide translation and its reverse, DNA probe design, and codon usage statistics. Since the calculator comes with built-in Kermit protocol, serial port, infrared interface, and sequences are in ASCII code, users can communicate sequences bench-to-bench to other calculators or upload and download them with IBM PC compatible and Macintosh computers.

6-Phosphofructo-2-kinase and fructose-2,6-bisphosphatase from Saccharomyces cerevisiae.

In permeabilized yeast cells 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase are studied during growth. It is shown that in yeast at least two fructose 2,6-bisphosphate degrading enzyme activities occur, differing in pH profile and in their substrate affinities. The activities of 6-phosphofructo-2-kinase and of fructose-2,6-bisphosphatases drop in the exponential and the transition phase while the activity of the alkaline phosphatases steadily increases. In the stationary phase the activities of 6-phosphofructo-2-kinase and of the low Km fructose-2,6-bisphosphatase increase again. Yeast 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase were purified and separated from each other. The purified 6-phosphofructo-2-kinase was found to exhibit a very high specific activity (1.3 U/mg). The enzyme is efficiently inhibited by ATP. The ATP inhibition is most pronounced at low concentrations of magnesium and fructose-6-phosphate. Phosphoenolpyruvate and sn-glycerol 3-phosphate are inhibitors of the enzyme. The high-affinity yeast fructose-2,6-bisphosphatase releases inorganic phosphate from the 2-position of fructose 2,6-bisphosphate. It displays hyperbolic kinetics towards fructose 2,6-bisphosphate (Km = 0.3 microM) and is strongly inhibited by fructose 6-phosphate. The inhibition is counteracted by sn-glycerol 3-phosphate. The enzyme is shown to be inactivated by cAMP-dependent phosphorylation and reactivated by the action of protein phosphatase 2A.

[Effects of lowest levels of drugs--a contribution to homeopathy research]. / Effekte kleinster Wirkstoffmengen--ein Beitrag zur Homöopathie-Forschung.

After oral administration of homoeopathically prepared low-dose-amounts of Conium and Mercury phosphate to male Wistar rats enzymatic parameters were investigated in three subcellular compartments of the liver under blind conditions. 1. After seven single application of the substance amount referring to a D8 potency a maximum effect could be detected for both agents. 2. The relation between agent and magnitude of the provoked effect is not linear. 3. The importance of these results is discussed and integrated into a general context.

Aimless mutants of Cryptococcus neoformans: failure to disseminate.

The pathogenic fungus Cryptococcus neoformans exhibits a striking propensity to cause central nervous system (CNS) disease in people with HIV/AIDS. Given that cryptococcal infections are generally initiated by pulmonary colonization, dissemination requires that the fungus withstand phagocytic killing, cross the alveolar-capillary interface in the lung, survive in the circulatory system and breach the blood-brain barrier. We know little about the molecular mechanisms underlying dissemination, but there is a rapidly growing list of mutants that fail to cause CNS disease. These mutants reveal a remarkable diversity of functions and therefore illustrate the complexity of the cryptococcal-host interaction. The challenge now is to extend the analysis of these mutants to acquire a detailed understanding of each step in dissemination.