Grundsatzfragen einer Reform der Verkehrspolitik

Entsprechend den Prognosen im „Verkehrsbericht 2000" wird in den kommenden 15 Jahren der Güterverkehr um mehr als 60% zunehmen. Dieses Wachstum kann nur von allen Verkehrsträgern nach einer grundlegenden Reform der Verkehrspolitik bewältigt werden. Wie könnte sie aussehen? --

Salivary PYY: A Putative Bypass to Satiety

Peptide YY3-36 is a satiation hormone released postprandially into the bloodstream from L-endocrine cells in the gut epithelia. In the current report, we demonstrate PYY3-36 is also present in murine as well as in human saliva. In mice, salivary PYY3-36 derives from plasma and is also synthesized in the taste cells in taste buds of the tongue. Moreover, the cognate receptor Y2R is abundantly expressed in the basal layer of the progenitor cells of the tongue epithelia and von Ebner's gland. The acute augmentation of salivary PYY3-36 induced stronger satiation as demonstrated in feeding behavioral studies. The effect is mediated through the activation of the specific Y2 receptor expressed in the lingual epithelial cells. In a long-term study involving diet-induced obese (DIO) mice, a sustained increase in PYY3-36 was achieved using viral vector-mediated gene delivery targeting salivary glands. The chronic increase in salivary PYY3-36 resulted in a significant long-term reduction in food intake (FI) and body weight (BW). Thus this study provides evidence for new functions of the previously characterized gut peptide PYY3-36 suggesting a potential simple and efficient alternative therapeutic approach for the treatment of obesity

ceritinib plus nivolumab in patients with advanced alk rearranged non small cell lung cancer results of an open label multicenter phase 1b study

Abstract Introduction Induction of programmed death ligand 1 (PD-L1) expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring echinoderm microtubule associated protein like 4 gene (EML4)–ALK receptor tyrosine kinase gene (ALK) rearrangements. We assessed the safety and activity of ceritinib plus nivolumab in these patients. Methods In this open-label, phase 1B, multicenter, dose escalation and expansion study, previously treated (with ALK receptor tyrosine kinase [ALK] inhibitor [ALKI]/chemotherapy) or treatment-naive patients with stage IIIB or IV ALK-rearranged NSCLC received nivolumab, 3 mg/kg intravenously every 2 weeks, plus ceritinib, 450 mg/300 mg daily, with a low-fat meal. Results In total, 36 patients were treated (a 450-mg cohort [n=14] and a 300-mg cohort [n=22]). In the 450-mg cohort, four patients experienced dose-limiting toxicities. In the 300-mg cohort, two patients experienced dose-limiting toxicities. Among ALKI-naive patients, the overall response rate (ORR) was 83% (95% confidence interval [CI]: 35.9–99.6) in the 450-mg cohort and 60% (95% CI: 26.2–87.8) in the 300-mg cohort. Among ALKI-pretreated patients, the ORR was 50% (95% CI: 15.7–84.3) in the 450-mg cohort and 25% (95% CI: 5.5–57.2) in the 300-mg cohort. The ORR point estimate was observed to be greater in patients who were positive for PD-L1 than in those who were negative for PD-L1, with overlapping CIs (e.g., at a cutoff ≥1% PD-L1, 64% of patients [95% CI: 35.1–87.2] had confirmed responses as compared with those with negative PD-L1 staining (31% [95% CI: 11.0–58.7]). The most frequently reported grade 3 or 4 adverse events were increased alanine aminotransferase level (25%), increased gamma-glutamyl transferase level (22%), increased amylase level (14%), increased lipase level (11%), and maculopapular rash (11%). The incidence of all-grade rash (grouped term) was 64% in both cohorts; grade 3 rash was reported in 29% and 14% of patients in the 450-mg and 300-mg cohorts, respectively; no grade 4 rash was reported. Conclusion Ceritinib plus nivolumab has activity; ORR appears to correlate with PD-L1 at baseline. Toxicity, especially rash, is more common than with either single agent

Salivary MUC5B-mediated adherence (Ex Vivo) of Helicobacter pylori during acute stress

OBJECTIVE: Biochemical host defenses at mucosal sites, such as the oral cavity, play a key role in the regulation of microbial ecology and the prevention of infectious disease. These biochemical factors have distinct features, some of which benefit the host and some that benefit bacteria. We investigated the effects of acute stress on the salivary levels of the carbohydrate structure sulfo-Lewis (sulfo-Le), which is linked to the mucosal glycoprotein MUC5B. Sulfo-Le was recently identified as an adhesion molecule for Helicobacter pylori; therefore, we also measured saliva-mediated adherence (ex vivo) of H. pylori. The oral cavity is suspected to be involved in the transmission of H. pylori. METHODS: Saliva was collected from 17 undergraduates before (baseline), during (stress), and after (recovery) exposure to a video showing surgical procedures. In addition, blood pressure, an impedance cardiogram, and an electrocardiogram were recorded. RESULTS: During stressor exposure, participants reported increased state anxiety. In addition, stroke volume increased and heart rate decreased. The stressor induced a strong increase in salivary sulfo-Le concentration (U/ml), sulfo-Le output (U/min), sulfo-Le/total protein ratio (U/mg protein), and saliva-mediated adherence (ex vivo) of H. pylori. As expected, sulfo-Le concentration correlated with the adherence of H. pylori (r = 0.72, p < .05). It was demonstrated that the observed adherence was induced by MUC5B and that the carbohydrate structure sulfo-Le contributed to this process

Laboratory Testing of Bulk Vitrified Low-Activity Waste Forms to Support the 2005 Integrated Disposal Facility Performance Assessment

The purpose of this report is to document the results from laboratory testing of the bulk vitri-fied (BV) waste form that was conducted in support of the 2005 integrated disposal facility (IDF) performance assessment (PA). Laboratory testing provides a majority of the key input data re-quired to assess the long-term performance of the BV waste package with the STORM code. Test data from three principal methods, as described by McGrail et al. (2000a; 2003a), are dis-cussed in this testing report including the single-pass flow-through test (SPFT) and product con-sistency test (PCT). Each of these test methods focuses on different aspects of the glass corrosion process. See McGrail et al. (2000a; 2003a) for additional details regarding these test methods and their use in evaluating long-term glass performance. In addition to evaluating the long-term glass performance, this report discusses the results and methods used to provided a recommended best estimate of the soluble fraction of 99Tc that can be leached from the engineer-ing-scale BV waste package. These laboratory tests are part of a continuum of testing that is aimed at improving the performance of the BV waste package

Multi-scale Inference of Interaction Rules in Animal Groups Using Bayesian Model Selection

Inference of interaction rules of animals moving in groups usually relies on an analysis of large scale system behaviour. Models are tuned through repeated simulation until they match the observed behaviour. More recent work has used the fine scale motions of animals to validate and fit the rules of interaction of animals in groups. Here, we use a Bayesian methodology to compare a variety of models to the collective motion of glass prawns (Paratya australiensis). We show that these exhibit a stereotypical ‘phase transition’, whereby an increase in density leads to the onset of collective motion in one direction. We fit models to this data, which range from: a mean-field model where all prawns interact globally; to a spatial Markovian model where prawns are self-propelled particles influenced only by the current positions and directions of their neighbours; up to non-Markovian models where prawns have ‘memory’ of previous interactions, integrating their experiences over time when deciding to change behaviour. We show that the mean-field model fits the large scale behaviour of the system, but does not capture fine scale rules of interaction, which are primarily mediated by physical contact. Conversely, the Markovian self-propelled particle model captures the fine scale rules of interaction but fails to reproduce global dynamics. The most sophisticated model, the non-Markovian model, provides a good match to the data at both the fine scale and in terms of reproducing global dynamics. We conclude that prawns' movements are influenced by not just the current direction of nearby conspecifics, but also those encountered in the recent past. Given the simplicity of prawns as a study system our research suggests that self-propelled particle models of collective motion should, if they are to be realistic at multiple biological scales, include memory of previous interactions and other non-Markovian effects

Investigation of Accelerated Casing Corrosion in Two Wells at Waste Management Area A-AX

This report was revised in September 2008 to remove acid-extractable sodium data from Tables 3.13 and 3.14. The sodium data was removed due to potential contamination introduced during the acid extraction process. The rest of the text remains unchanged from the original report issued in August 2005. An overall goal of the Groundwater Performance Assessment Project, led by Pacific Northwest National Laboratory (PNNL) and per guidance in DOE Order 5400.1, includes characterizing and defining trends in the physical, chemical, and biological condition of the environment. To meet these goals, numerous Resource Conservation and Recovery Act (RCRA) monitoring wells have been installed throughout the Hanford Site. In 2003, it was determined that two RCRA monitoring wells (299-E24-19 and 299-E25-46) in Waste Management Area (WMA) A-AX failed due to rapid corrosion of the stainless steel casing over a significant length of the wells. Complete casing corrosion occurred between 276.6 and 277.7 feet below ground surface (bgs) in well 299- E24-19 and from 274.4 to 278.6 feet bgs in well 299-E25-46. CH2M HILL Hanford Group, Inc., asked scientists from PNNL to perform detailed analyses of vadose zone sediment samples collected in the vicinity of the WMA A-AX from depths comparable to those where the rapid corrosion occurred in hopes of ascertaining the cause of the rapid corrosion

Reduced volume of the arcuate fasciculus in adults with high-functioning autism spectrum conditions

Atypical language is a fundamental feature of autism spectrum conditions (ASC), but few studies have examined the structural integrity of the arcuate fasciculus, the major white matter tract connecting frontal and temporal language regions, which is usually implicated as the main transfer route used in processing linguistic information by the brain. Abnormalities in the arcuate have been reported in young children with ASC, mostly in low-functioning or non-verbal individuals, but little is known regarding the structural properties of the arcuate in adults with ASC or, in particular, in individuals with ASC who have intact language, such as those with high-functioning autism or Asperger syndrome. We used probabilistic tractography of diffusion-weighted images (DWI) to isolate and scrutinise the arcuate in a mixed-gender sample of 18 high-functioning adults with ASC (17 Asperger syndrome) and 14 age- and IQ-matched typically-developing controls. Arcuate volume was significantly reduced bilaterally with clearest differences in the right hemisphere. This finding remained significant in an analysis of all male participants alone. Volumetric reduction in the arcuate was significantly correlated with the severity of autistic symptoms as measured by the Autism-Spectrum Quotient. These data reveal that structural differences are present even in high-functioning adults with ASC, who presented with no clinically manifest language deficits and had no reported developmental language delay. Arcuate structural integrity may be useful as an index of ASC severity and thus as a predictor and biomarker for ASC. Implications for future research are discussed

Characterization of Vadose Zone Sediment: Borehole 299-E33-45 Near BX-102 in the B-BX-BY Waste Management Area

This report was revised in September 2008 to remove acid-extractable sodium data from Table 4.22. The data was removed due to potential contamination introduced during the acid extraction process. The remaining text is unchanged from the original report issued in 2002. The overall goal of the Tank Farm Vadose Zone Project, led by CH2M HILL Hanford Group, Inc., is to define risks from past and future single-shell tank farm activities. To meet this goal, CH2M HILL Hanford Group, Inc., asked scientists from Pacific Northwest National Laboratory to perform detailed analyses on vadose zone sediments from within Waste Management Area B-BX-BY. This report is the first in a series of four reports to present the results of these analyses. Specifically, this report contains all the geologic, geochemical, and selected physical characterization data collected on vadose zone sediment recovered from borehole 299-E33-45 installed northeast of tank BX-102

Characterization of Vadose Zone Sediments Below the T Tank Farm: Boreholes C4104, C4105, 299-W10-196, and RCRA Borehole 299-W11-39

This report was revised in September 2008 to remove acid-extractable sodium data from Tables 4.8, 4.28, and 4.52. The sodium data was removed due to potential contamination introduced during the acid extraction process. The rest of the text remains unchanged from the original report issued in September 2004. The overall goal of the Tank Farm Vadose Zone Project, led by CH2M HILL Hanford Group, Inc., is to define risks from past and future single-shell tank farm activities at Hanford. To meet this goal, CH2M HILL Hanford Group, Inc. tasked scientists from Pacific Northwest National Laboratory to perform detailed analyses on vadose zone sediments from within Waste Management Area (WMA) T-TX-TY. This report is the second of two reports written to present the results of these analyses. Specifically, this report contains all the geologic, geochemical, and selected physical characterization data collected on vadose zone sediment recovered from boreholes C4104 and C4105 in the T Tank Farm, and from borehole 299-W-11-39 installed northeast of the T Tank Farm. Finally, the measurements on sediments from borehole C4104 are compared with a nearby borehole drilled in 1993, 299- W10-196, through the tank T-106 leak plume