The Line-haul Feeder Vehicle Routing Problem: Mathematical model formulation and heuristic approaches

This paper deals with a rather new version of the well known Vehicle Routing Problem (VRP) called the Line-haul Feeder Vehicle Routing Problem (LFVRP). It can be described as a VRP with synchronization constraints where two types of customers are served by two types of vehicles. These vehicles, contrary to the regular VRP, can meet and perform a transshipment to extend their travel. To achieve that, the vehicles need to synchronise – meaning that they have to be at the same place at the same time. The objective of the LFVRP is to minimize the total cost consisting of fixed vehicle cost as well as variable fuel and wage costs for drivers. For this problem we propose the first general mathematical model and derive two heuristics inspired by some structural insights about the problem. Using a thorough and comprehensive computational analysis we show the benefits of the LFVRP over simpler VRP variants, the quality of the heuristics compared with earlier work on the LFVRP and the relative performance of the two heuristics described as a function of different problem characteristics

Mikrobieller Abbau von Buchenstreu unterschiedlicher Herkunft

In temperaten Ökosystemen durchläuft ein großer Teil der Primärproduktion den Laubfall. Laubstreu liefert eine wichtige Nährstoffgrundlage für das Bodenleben und in weiterer Folge durch Abbauprozesse wieder für die Pflanzen. Die elementare chemische Zusammensetzung und die chemische Veränderung der Laubstreu während des Abbauprozesses spielen eine große Rolle in der Natur. Im Laufe des Abbaus werden leichter abbaubare Kohlenhydrate veratmet und schwer degradierbare hochpolymere Substanzen reichern sich an. Durch die Besiedelung von Mikroorganismen und deren aktiven Metabolismus werden dem restlichen Ökosystem viele wertvolle Nährstoffe für die Wieder-Aufnahme verfügbar gemacht. Dieser Prozess unterliegt vielen natürlichen Einflüssen, die durch die Verwendung eines Mikrokosomos-Systems verringert wurden. Die beiden großen Einflussfaktoren Temperatur und Feuchtigkeit wurden im vorliegenden Versuch nahezu konstant gehalten. Das Ziel dieser Arbeit war es, den Einfluss der unterschiedlichen Nährelementzusammensetzung der verwendeten Buchenlaubstreu (Fagus sylvatica L.) auf den Abbau zu untersuchen. Dafür wurden 60 Mikrokosmen konstruiert, in denen je 38 g Laubstreu über eine Periode von acht Wochen inkubiert wurden. Die Auswirkungen der Herkunft und der elementaren Zusammensetzung der Laubstreu auf die Nährstofffreisetzung wurden untersucht. Es wurden mikrobielle Biomasse nach Chloroform-Fumigation, Kohlendioxid, Methan, Lachgas, Ammonium und Nitrat in wöchentlichen Intervallen und Phospholipidfettsäuren (PLFS) zu drei Zeitpunkten gemessen. Der Fokus der vorliegenden Arbeit lag auf dem zeitlichen Ablauf des Abbaus, dem Einfluss der ursprünglichen Nährstoff-Stöchiometrie auf den Abbauprozess und mikrobiellen Interaktionen und Verschiebungen in der Gemeinschaft. Ein wichtiger Aspekt war die Akkumulation von Stickstoff in der mikrobiellen Biomasse. Es konnten einige der untersuchten Variablen miteinander in Beziehung gesetzt werden. Die Ammonium-Konzentration war mit der mikrobiellen Biomasse stark negativ korreliert, und die Respiration war schwach mit der Nitratkonzentration korreliert. Die mikrobielle Gemeinschaft veränderte sich von sog. r-Strategen (gram-) in Richtung K-Strategen (gram+ und Pilze). Es wurde außerdem ein Antagonismus zwischen Pilzen und Aktinomyceten gezeigt. Sehr deutlich war auch der Rückgang an Aktivität: so wurde bei den meisten Standorten zu Beginn am meisten geatmet, und im Verlauf der acht Wochen immer weniger. Diese Beobachtung lässt sich auf die sich ändernde chemische Zusammensetzung während des Laubabbaus zurückführen. Die Zunahme von mikrobieller Biomasse war zu Beginn am stärksten und veränderte sich im weiteren Verlauf des Versuchs nur marginal. Lachgas und Methan waren nur in sehr kleinen Konzentrationen vorhanden, was darauf hindeutet, dass das System durchwegs aerob war. Durch den Versuch wurde gezeigt, dass es einen Unterschied macht, ob in der Streu der Stickstoff als Ammonium oder Nitrat vorliegt. In unserem Fall hatten Standorte mit höherem Ammonium-Gehalt weniger Respiration. Auch der Einfluss anderer Nährelemente, wie Kalium oder möglicherweise sogar Mangan spielte eine Rolle. So hatten Standorte mit höherem Ammoniumgehalt zusätzlich wenig Kalium und Mangan. Die interessanteste Erktenntnis war, dass die weit verbreitete Meinung, dass die Gesamtstickstoffkonzentration der bestimmende Faktor für die Abbaugeschwindigkeit von Laubstreu ist, in unserem Versuch nicht bestätigt werden konnte.In this study the influence of initial elemental stoichiometry of beech (Fagus sylvatica L.) litter on microbial decomposition was investigated. Litter from four different Austrian sites with different elemental stoichiometry was examined. A detailed perspective on early litter decomposition was provided: Sixty litter microcosms were sampled over eight weeks in total. Decomposition rates found in our laboratory experiment were in the range of literature values and consistent with in situ litter bag studies. In addition to decomposition in terms of CO2 respiration and litter mass loss the focus laid on microbial nitrogen uptake and microbial interactions. The results showed, that the chemical nature of mineral nitrogen was more important than initial total nitrogen concentrations. Sites with higher amounts of initial ammonium were less active than sites with more initial nitrate. Microbial community analysis (Phospholipid Fatty Acids) revealed contrasting behaviour of fungi and actinomycetes during litter decomposition. Additionally the potassium and possibly also the manganese content of the litter affected the decomposition dynamics. Microbial biomass increased and the inorganic nitrogen pools decreased in the very beginning of the experiment. Respiration was also highest in the beginning, indicating highest activity at the start of the experiment. Not only the amount but also the form of nitrogen release strongly influenced the decomposition process

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

Structurally and functionally unique complexins at retinal ribbon synapses

Ribbon synapses in retinal sensory neurons maintain large pools of readily releasable synaptic vesicles. This allows them to release several hundreds of vesicles per second at every presynaptic release site. The molecular components that cause this high transmitter release efficiency of ribbon synapses are unknown. In the present study, we identified and characterized two novel vertebrate complexins (CPXs), CPXs III and IV, that are the only CPX isoforms present in retinal ribbon synapses. CPXs III and IV are COOH-terminally farnesylated, and, like CPXs I and II, bind to SNAP receptor complexes. CPXs III and IV can functionally replace CPXs I and II, and their COOH-terminal farnesylation regulates their synaptic targeting and modulatory function in transmitter release. The novel CPXs III and IV may contribute to the unique release efficacy of retinal sensory neurons

On the possible contribution of meteoritic metal to Ni-rich Indonesian kris daggers:Comparing original daggers and newly forged analog objects

The “Weltmuseum Wien” owns a large collection of kris daggers from Indonesia. These objects are famous for their metal blades consisting of numerous layers made by a complicated forging process involving repeated folding and welding of the individual layers. There is a widespread belief that some krises were manufactured by adding meteoritic nickel–iron from the Prambanan meteorite that fell in Central Java and is known since the late 18th century. In our study, we investigated a selection of five Ni-rich krises from this collection with the aim to identify in their blades nickel–iron from Prambanan or another iron meteorite source. To obtain a better insight into the forging process, we investigated analog objects that were produced by a forging procedure similar to the one applied in the production of original krises and by using iron meteorite material from the meteorites Campo del Cielo and Gibeon as admixture. These investigations were performed by nondestructive analytical techniques, including handheld X-ray fluorescence (HH-XRF) analysis, scanning electron microscopy (SEM), and electron microprobe (EMP) analysis. The original daggers were investigated by HH-XRF and micro-X-ray fluorescence (μ-XRF) analysis, as well as by portable laser ablation (pLA) subsampling followed by trace element analysis using inductively coupled plasma mass spectrometry (ICP-MS). By comparing the data obtained for both materials, we demonstrate that the main difficulties in identifying the presence of a meteoritic component in the kris daggers are due to the exclusive use of (quasi-)nondestructive methods in combination with locally varying surface heterogeneities, resulting from contamination, corrosion, and etching features. We also show that the presence of significant amounts of Ni and Co (in the wt% range) in a premodern kris dagger does not imply that it was manufactured with an admixture of meteoritic metal. We found that among the five krises investigated, only a single dagger (no. 900382) was manufactured with the possible admixture of nickel–iron from the Prambanan iron meteorite, as it contains high concentrations of siderophile elements and has a Ni/Co ratio comparable to that of the meteorite.</p

CONAN: copy number variation analysis software for genome-wide association studies

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies (GWAS) based on single nucleotide polymorphisms (SNPs) revolutionized our perception of the genetic regulation of complex traits and diseases. Copy number variations (CNVs) promise to shed additional light on the genetic basis of monogenic as well as complex diseases and phenotypes. Indeed, the number of detected associations between CNVs and certain phenotypes are constantly increasing. However, while several software packages support the determination of CNVs from SNP chip data, the downstream statistical inference of CNV-phenotype associations is still subject to complicated and inefficient in-house solutions, thus strongly limiting the performance of GWAS based on CNVs.</p> <p>Results</p> <p>CONAN is a freely available client-server software solution which provides an intuitive graphical user interface for categorizing, analyzing and associating CNVs with phenotypes. Moreover, CONAN assists the evaluation process by visualizing detected associations via Manhattan plots in order to enable a rapid identification of genome-wide significant CNV regions. Various file formats including the information on CNVs in population samples are supported as input data.</p> <p>Conclusions</p> <p>CONAN facilitates the performance of GWAS based on CNVs and the visual analysis of calculated results. CONAN provides a rapid, valid and straightforward software solution to identify genetic variation underlying the 'missing' heritability for complex traits that remains unexplained by recent GWAS. The freely available software can be downloaded at <url>http://genepi-conan.i-med.ac.at</url>.</p

Functional analyses of Pericentrin and Syne-2/Nesprin-2 interaction in ciliogenesis

Pericentrin (Pcnt) is a multifunctional scaffold protein and mutations in the human PCNT gene are associated with several diseases, including ciliopathies. Pcnt plays a crucial role in ciliary development in olfactory receptor neurons, but its function in the photoreceptor-connecting cilium is unknown. We downregulated Pcnt in the retina ex vivo and in vivo via a virus-based RNA interference approach to study Pcnt function in photoreceptors. ShRNA-mediated knockdown of Pcnt impaired the development of the connecting cilium and the outer segment of photoreceptors, and caused a nuclear migration defect. In protein interaction screens, we found that the outer nuclear membrane protein Syne-2 (also known as Nesprin-2) is an interaction partner of Pcnt in photoreceptors. Syne-2 is important for positioning murine photoreceptor cell nuclei and for centrosomal migration during early ciliogenesis. CRISPR/Cas9-mediated knockout of Syne-2 in cell culture led to an overexpression and mislocalization of Pcnt and to ciliogenesis defects. Our findings suggest that the Pcnt–Syne-2 complex is important for ciliogenesis and outer segment formation during retinal development and plays a role in nuclear migration

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Similarities in element content between comet 67P/Churyumov–Gerasimenko coma dust and selected meteorite samples

We have analysed the element composition and the context of particles collected within the coma of 67P/Churyumov–Gerasimenko with Rosetta’s COmetary Secondary Ion Mass Analyzer (COSIMA). A comparison has been made between on board cometary samples and four meteorite samples measured in the laboratory with the COSIMA reference model. Focusing on the rock-forming elements, we have found similarities with chondrite meteorites for some ion count ratios. The composition of 67P/Churyumov–Gerasimenko particles measured by COSIMA shows an enrichment in volatile elements compared to that of the investigated Renazzo (CR2) carbonaceous meteorite sample.</p

Limitations of Fe^(2+) and Mn^(2+) site occupancy in tourmaline: Evidence from Fe^(2+)- and Mn^(2+)-rich tourmaline

Fe^(2+)- and Mn^(2+)-rich tourmalines were used to test whether Fe^(2+) and Mn^(2+) substitute on the Z site of tourmaline to a detectable degree. Fe-rich tourmaline from a pegmatite from Lower Austria was characterized by crystal-structure refinement, chemical analyses, and Mössbauer and optical spectroscopy. The sample has large amounts of Fe^(2+) (~2.3 apfu), and substantial amounts of Fe^(3+) (~1.0 apfu). On basis of the collected data, the structural refinement and the spectroscopic data, an initial formula was determined by assigning the entire amount of Fe^(3+) (no delocalized electrons) and Ti^(4+) to the Z site and the amount of Fe^(2+) and Fe^(3+) from delocalized electrons to the Y-Z ED doublet (delocalized electrons between Y-Z and Y-Y): X(Na_(0.9)Ca_(0.1)) ^Y(Fe^(2+)_(2.0)Al_(0.4)Mn^(2+)_(0.3)Fe^(3+)_(0.2)) ^Z(Al_(4.8)Fe^(3+)_(0.8)Fe^(2+)_(0.2)Ti^(4+)_(0.1)) ^T(Si_(5.9)Al_(0.1))O_(18) (BO_3)_3^V(OH)_3 ^W[O_(0.5)F_(0.3)(OH)_(0.2)] with α = 16.039(1) and c = 7.254(1) Å. This formula is consistent with lack of Fe^(2+) at the Z site, apart from that occupancy connected with delocalization of a hopping electron. The formula was further modified by considering two ED doublets to yield: ^X(Na_(0.9)Ca_(0.1)) ^Y(Fe^(2+)_(1.8)Al_(0.5)Mn^(2+)_(0.3)Fe^(3+)_(0.3)) ^Z(Al_(4.8)Fe^(3+)_(0.7)Fe^(2+)_(0.4)Ti^(4+)_(0.1)) ^T(Si_(5.9_Al_(0.1))O_(18) (BO_3)_3 ^V(OH)_3 ^W[O_(0.5)F_(0.3)(OH)_(0.2)]. This formula requires some Fe^(2+) (~0.3 apfu) at the Z site, apart from that connected with delocalization of a hopping electron. Optical spectra were recorded from this sample as well as from two other Fe^(2+)-rich tourmalines to determine if there is any evidence for Fe^(2+) at Y and Z sites. If Fe^(2+) were to occupy two different 6-coordinated sites in significant amounts and if these polyhedra have different geometries or metal-oxygen distances, bands from each site should be observed. However, even in high-quality spectra we see no evidence for such a doubling of the bands. We conclude that there is no ultimate proof for Fe^(2+) at the Z site, apart from that occupancy connected with delocalization of hopping electrons involving Fe cations at the Y and Z sites. A very Mn-rich tourmaline from a pegmatite on Elba Island, Italy, was characterized by crystal-structure determination, chemical analyses, and optical spectroscopy. The optimized structural formula is ^X(Na_(0.6)□_(0.4)) ^Y(Mn^(2+)_(1.3)Al_(1.2)Li_(0.5)) ^ZAl_6 ^TSi_6O_(18) (BO_3)_3 ^V(OH)_3 ^W[F_(0.5)O_(0.5)], with α = 15.951(2) and c = 7.138(1) Å. Within a 3σ error there is no evidence for Mn occupancy at the Z site by refinement of Al ↔ Mn, and, thus, no final proof for Mn^(2+) at the Z site, either. Oxidation of these tourmalines at 700–750 °C and 1 bar for 10–72 h converted Fe^(2+) to Fe^(3+) and Mn^(2+) to Mn^(3+) with concomitant exchange with Al of the Z site. The refined ^ZFe content in the Fe-rich tourmaline increased by ~40% relative to its initial occupancy. The refined YFe content was smaller and the distance was significantly reduced relative to the unoxidized sample. A similar effect was observed for the oxidized Mn^(2+)-rich tourmaline. Simultaneously, H and F were expelled from both samples as indicated by structural refinements, and H expulsion was indicated by infrared spectroscopy. The final species after oxidizing the Fe^(2+)-rich tourmaline is buergerite. Its color had changed from blackish to brown-red. After oxidizing the Mn^(2+)-rich tourmaline, the previously dark yellow sample was very dark brown-red, as expected for the oxidation of Mn^(2+) to Mn^(3+). The unit-cell parameter α decreased during oxidation whereas the c parameter showed a slight increase