Synchronizing vans and cargo bikes in a city distribution network

One of the significant side-effects of growing urbanization is the constantly increasing amount of freight transportation in cities. This is mainly performed by conventional vans and trucks and causes a variety of problems such as road congestion, noise nuisance and pollution. Yet delivering goods to residents is a necessity. Sustainable concepts of city distribution networks are one way of mitigating difficulties of freight services. In this paper we develop a two-echelon city distribution scheme with temporal and spatial synchronization between cargo bikes and vans. The resulting heuristic is based on a greedy randomized adaptive search procedure with path relinking. In our computational experiments we use artificial data as well as real-world data of the city of Vienna. Furthermore we compare three distribution policies. The results show the costs caused by temporal synchronization and can give companies decision-support in planning a sustainable city distribution concept

Impact of travel time uncertainties on the solution cost of a two-echelon vehicle routing problem with synchronization

Two-echelon vehicle routing problems which contain synchronization between vehicles can be deeply impacted by time uncertainty, because one vehicle's delay can propagate to other vehicles. In this paper, we evaluate the deterministic solution of such a problem based on simulated travel time scenarios. The information obtained by simulation is incorporated in the optimization procedure iteratively. Computational results show that the degree of synchronization in an instance is directly correlated with the potential improvements by reoptimization. We present findings on the number of travel time scenarios required to obtain a representative picture of the stochastic solutions. In addition, we demonstrate that time dependent travel times can be aggregated on a city-wide level and linearized as a function of free flow times without major loss of reliability

Multi-objective optimization of a two-echelon vehicle routing problem with vehicle synchronization and "grey Zone" customers arising in urban logistics

We present a multi-objective two-echelon vehicle routing problem with vehicle synchronization and "grey zone" customers arising in the context of urban freight deliveries. Inner-city center deliveries are performed by small vehicles due to access restrictions, while deliveries outside this area are carried out by conventional vehicles for economic reasons. Goods are transferred from the first to the second echelon by synchronized meetings between vehicles of the respective echelons. We investigate the assignment of customers to vehicles, i.e., to the first or second echelon, within a so-called "grey Zone" on the border of the inner city and the area around it. While doing this, the economic objective as well as negative external effects of transport, such as emissions and disturbance (negative impact on citizens due to noise and congestion), are taken into account to include objectives of companies as well as of citizens and municipal authorities. Our metaheuristic - a large neighborhood search embedded in a heuristic rectangle/cuboid splitting - addresses this problem efficiently. We investigate the impact of the free assignment of part of the customers ("grey Zone") to echelons and of three different city layouts on the solution. Computational results show that the impact of a "grey Zone" and thus the assignment of these customers to echelons depend significantly on the layout of a city. Potentially pareto-optimal solutions for two and three objectives are illustrated to efficiently support decision makers in sustainable city logistics planning processes

Mosquito Populations from Eastern South Dakota During 2001 and 2002

In 2001, the South Dakota Department of Health initiated a program to monitor mosquitoes in South Dakota for the presence of the West Nile Virus. During the first year (2001), a pilot survey was conducted near Brookings, SD. To collect mosquitoes, CDC miniture light traps were used without carbondioxide baiting, beginning on July 3 and ending on August 2, 2001. Results from this small study (total of 2,042 mosquitoes during 10 collection days) showed that the most common mosquotes were Aedes vexans (88.2%), Culex tarsalis, (5.2%), and Aedes dorsalis (4.9%). An additional survey was conducted during the summer of 2002 focusing on 8 different sites (Brandon, Brookings, Huron, North Sioux City, Oak Lake Field Station, Watertown, Waubay and Yankton) in eastern South Dakota. Mosquitoes were collected with the same traps used for 2001, however, the traps were baited with carbon diaoxide (dry ice). Trapping began on June 1 and ended on September 1, 2002. A total of 18,971 mosquitoes were collected from the 8 sites during the 127 trapping days of this survey. From this population, 21 different mosquito species from 8 different genera were identified. The vast majority of mosquitoes were Aedes vexans (86.3%), but Culex tarsalis was also present in significant numbers (7.2%). Aedes vexans populations varied to a greater degree during the summer than did Culex tarsalis. The public’s perceptions of the danger of West Nile Virus transmission is probably more determined by Aedes population than by Culex populations even though Aedes likely plays little or no role in the transmission of this disease

Increased 5-hydroxymethylation levels in the sub ventricular zone of the Alzheimer's brain

© 2016 The Authors. The subventricular zone (SVZ) is a site of neurogenesis in the aging brain, and epigenetic mechanisms have been implicated in regulating the "normal" distribution of new nerve cells into the existing cellular milieu. In a case-control study of human primary SVZ cultures and fixed tissue from the same individuals, we have found significant increases in DNA hydroxymethylation levels in the SVZ of Alzheimer's disease patients compared with nondiseased control subjects. We show that this increase in hydroxymethylation directly correlates to an increase in cellular proliferation in Alzheimer's disease precursor cells, which implicates the hydroxymethylation tag to a higher degree of cellular proliferation

Type 2 Endoleaks: The Diagnostic Performance of Non-Specialized Readers on Arterial and Venous Phase Multi-Slice CT Angiography.

PURPOSE: To define the diagnostic precision of non-specialized readers in the detection of type 2 endoleaks (T2EL) in arterial versus venous phase acquisitions, and to evaluate an approach for radiation dose reduction. METHODS: The pre-discharge and final follow-up multi-slice CT angiographies of 167 patients were retrospectively analyzed. Image data were separated into an arterial and a venous phase reading set. Two radiology residents assessed the reading sets for the presence of a T2EL, feeding vessels, and aneurysm sac size. Findings were compared with a standard of reference established by two experts in interventional radiology. The effective dose was calculated. RESULTS: Overall, experts detected 131 T2ELs, and 331 feeding vessels in 334 examinations. Persistent T2ELs causing aneurysm sac growth > 5 mm were detected in 20 patients. Radiation in arterial and venous phases contributed to a mean of 58.6% and 39.0% of the total effective dose. Findings of reader 1 and 2 showed comparable sensitivities in arterial sets of 80.9 versus 85.5 (p = 0.09), and in venous sets of 73.3 versus 79.4 (p = 0.15), respectively. Reader 1 and 2 achieved a significant higher detection rate of feeding vessels with arterial compared to venous set (p = 0.04, p < 0.01). Both readers correctly identified T2ELs with growing aneurysm sac in all cases, independent of the acquisition phase. CONCLUSION: Arterial acquisitions enable non-specialized readers an accurate detection of T2ELs, and a significant better identification of feeding vessels. Based on our results, it seems reasonable to eliminate venous phase acquisitions

Correction: Type 2 Endoleaks: The Diagnostic Performance of Non-Specialized Readers on Arterial and Venous Phase Multi-Slice CT Angiography.

[This corrects the article DOI: 10.1371/journal.pone.0149725.]

Evaluation of [18F]-FDG-Based Hybrid Imaging Combinations for Assessment of Bone Marrow Involvement in Lymphoma at Initial Staging.

The purpose of our study was to determine the value of different hybrid imaging combinations for the detection of focal and diffuse bone marrow infiltration in lymphoma. Patients with histologically proven lymphoma, who underwent both [18F]-FDG-PET/CT and whole-body MRI (including T1- and diffusion-weighted [DWI] sequences) within seven days, and a subsequent bone marrow biopsy, were retrospectively included. Three hybrid imaging combinations were evaluated: (1) [18F]-FDG-PET/CT; (2) [18F]-FDG-PET/T1; and (3) [18F]-FDG-PET/DWI. The presence of focal or diffuse bone marrow infiltration was assessed by two rater teams. Sensitivity, specificity, and accuracy for the detection of overall, focal, and diffuse bone marrow involvement were compared between the three hybrid imaging combinations. Overall, lymphomatous bone marrow involvement was found in 16/60 patients (focal, 8; diffuse, 8). Overall sensitivity, specificity, and accuracy were 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/CT; 81.3%, 97.7%, and 93.3% for [18F]-FDG-PET/T1; and 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/DWI. No statistically significant differences between the three imaging combinations were observed, based on overall bone marrow involvement, focal involvement, or diffuse involvement. The sensitivity of all three imaging combinations for detecting diffuse bone marrow involvement was only moderate (62.5% for all three combinations). Although the combination of [18F]-FDG-PET and T1-weighted MRI generally showed the best diagnostic performance for the detection of bone marrow involvement in lymphoma, it was not significantly superior to the two other hybrid imaging combinations. Since the sensitivity of all imaging combinations for the detection of diffuse bone marrow involvement was only moderate, bone marrow biopsy cannot be replaced by imaging as yet

The secreted protein Cowpox Virus 14 contributes to viral virulence and immune evasion by engaging Fc-gamma-receptors

The genome of cowpoxvirus (CPXV) could be considered prototypical for orthopoxviridae (OXPV) since it contains many open reading frames (ORFs) absent or lost in other OPXV, including vaccinia virus (VACV). These additional ORFs are non-essential for growth in vitro but are expected to contribute to the broad host range, virulence and immune evasion characteristics of CPXV. For instance, unlike VACV, CPXV encodes proteins that interfere with T cell stimulation, either directly or by preventing antigen presentation or co-stimulation. When studying the priming of naïve T cells, we discovered that CPXV, but not VACV, encodes a secreted factor that interferes with activation and proliferation of naïve CD8+ and CD4+ T cells, respectively, in response to anti-CD3 antibodies, but not to other stimuli. Deletion mapping revealed that the inhibitory protein is encoded by CPXV14, a small secreted glycoprotein belonging to the poxvirus immune evasion (PIE) family and containing a smallpoxvirus encoded chemokine receptor (SECRET) domain that mediates binding to chemokines. We demonstrate that CPXV14 inhibition of antibody-mediated T cell activation depends on the presence of Fc-gamma receptors (FcγRs) on bystander cells. In vitro, CPXV14 inhibits FcγR-activation by antigen/antibody complexes by binding to FcγRs with high affinity and immobilized CPXV14 can trigger signaling through FcγRs, particularly the inhibitory FcγRIIB. In vivo, CPXV14-deleted virus showed reduced viremia and virulence resulting in reduced weight loss and death compared to wildtype virus whereas both antibody and CD8+ T cell responses were increased in the absence of CPXV14. Furthermore, no impact of CPXV14-deletion on virulence was observed in mice lacking the inhibitory FcγRIIB. Taken together our results suggest that CPXV14 contributes to virulence and immune evasion by binding to host FcγRs

Targeted methylation profiling of single laser-capture microdissected post-mortem brain cells by adapted limiting dilution bisulfite pyrosequencing (LDBSP)

A reoccurring issue in neuroepigenomic studies, especially in the context of neurodegenerative disease, is the use of (heterogeneous) bulk tissue, which generates noise during epigenetic profiling. A workable solution to this issue is to quantify epigenetic patterns in individually isolated neuronal cells using laser capture microdissection (LCM). For this purpose, we established a novel approach for targeted DNA methylation profiling of individual genes that relies on a combination of LCM and limiting dilution bisulfite pyrosequencing (LDBSP). Using this approach, we determined cytosine-phosphate-guanine (CpG) methylation rates of single alleles derived from 50 neurons that were isolated from unfixed post-mortem brain tissue. In the present manuscript, we describe the general workflow and, as a showcase, demonstrate how targeted methylation analysis of various genes, in this case, RHBDF2, OXT, TNXB, DNAJB13, PGLYRP1, C3, and LMX1B, can be performed simultaneously. By doing so, we describe an adapted data analysis pipeline for LDBSP, allowing one to include and correct CpG methylation rates derived from multi-allele reactions. In addition, we show that the efficiency of LDBSP on DNA derived from LCM neurons is similar to the efficiency obtained in previously published studies using this technique on other cell types. Overall, the method described here provides the user with a more accurate estimation of the DNA methylation status of each target gene in the analyzed cell pools, thereby adding further validity to this approach