Lagrangian-based Hydrodynamic Model for Traffic Data Fusion on Freeways

This paper conducts a comprehensive study of the Lagrangian-based hydrodynamic model with application to highway state estimation. Our analysis is motivated by the practical problems of freeway traffic monitoring and estimation using multi-source data measured from mobile devices and fixed sensors. We conduct rigorous mathematical analysis on the Hamilton-Jacobi representation of the Lighthill-Whitham-Richards model in the transformed coordinates, and derive explicit and closed-form solutions with piecewise affine initial, boundary, and internal conditions, based on the variational principle. A numerical study of the Mobile Century field experiment demonstrates some unique features and the effectiveness in traffic estimation of the Lagrangian-based model

In Situ Structure Characterization in Slot-Die-Printed All-Polymer Solar Cells with Efficiency Over 9%

Herein, high-performance printed all-polymer solar cells (all-PSCs) based on a bulk-heterojunction (BHJ) blend film are demonstrated using PTzBI as the donor and N2200 as the acceptor. A slot-die process is used to prepare the BHJ blend, which is a cost-effective, high-throughput approach to achieve large-area photovoltaic devices. The real-time crystallization of polymers in the film drying process is investigated by in situ grazing incidence wide-angle X-ray scattering characterization. Printing is found to significantly improve the crystallinity of the polymer blend in comparison with spin coating. Moreover, printing with 1,8-diiodooctane as the solvent additive enhances the polymer aggregation and crystallization during solvent evaporation, eventually leading to multi-length-scale phase separation, with PTzBI-rich domains in-between the N2200 crystalline fibers. This unique morphology achieved by printing fabrication results in an impressively high power conversion efficiency of 9.10%, which is the highest efficiency reported for printed all-PSCs. These findings provide important guidelines for controlling film drying dynamics for processing all-PSCs

Multiscale correlative tomography: an investigation of creep cavitation in 316 stainless steel

Creep cavitation in an ex-service nuclear steam header Type 316 stainless steel sample is investigated through a multiscale tomography workflow spanning eight orders of magnitude, combining X-ray computed tomography (CT), plasma focused ion beam (FIB) scanning electron microscope (SEM) imaging and scanning transmission electron microscope (STEM) tomography. Guided by microscale X-ray CT, nanoscale X-ray CT is used to investigate the size and morphology of cavities at a triple point of grain boundaries. In order to understand the factors affecting the extent of cavitation, the orientation and crystallographic misorientation of each boundary is characterised using electron backscatter diffraction (EBSD). Additionally, in order to better understand boundary phase growth, the chemistry of a single boundary and its associated secondary phase precipitates is probed through STEM energy dispersive X-ray (EDX) tomography. The difference in cavitation of the three grain boundaries investigated suggests that the orientation of grain boundaries with respect to the direction of principal stress is important in the promotion of cavity formation

Unique pattern of infections in chronic granulomatous disease – The Asian experience

Conference Theme: Inflammatory Basis of Perinatal and Childhood DiseasesSymposium 40: InfectionBackground: Chronic granulomatous disease (CGD) is a phagocytic disorder caused by defective NADPH oxidase activity. Affected individuals are susceptible to bacterial infections, mycosis and hyperinflammatory complications. Variations in the epidemiology of infectious diseases across geographical regions can lead to distinct clinical phenotypes. Objective: To identify the unique clinical characteristics of a large cohort of CGD patients in China and Southeast Asia referred for genetic studies from 2003 to 2012. Methods: 53 patients with genetically-confirmed CGD were included and their clinical features were analyzed. CYBB and CYBA mutations were studied by Sanger sequencing, and NCF1 ‘GT’ deletion hotspot mutation was studied on genomic DNA by GeneScan. Results: 44 patients with X-CGD had CYBB mutations (missense[n=16]; nonsense[n=8]; deletion[n=9]; insertion[n=2]; intron mutation[n=9]). Nine patient had AR-CGD (CYBA[n=5]; NCF1 75_76delGT[n=4]). The median age at presentation and diagnosis was higher in AR-CGD (7m and 66m) compared with X-CGD (3m and 22m). The commonest presentations were pneumonia (58%), skin and perianal abscess (49%), lymphadenitis (42%) and recurrent diarrhea (30%). Aspergillosis and salmonellosis occurred at a frequency similar to published studies (13% and 19% respectively), but the commonest infection was BCG (43%) and 11% had disseminated BCG. 21% of patients had tuberculosis. Fulminant melioidosis and Chromobacterium violaceum infections occurred in 3 patients and two of their male siblings. Hyperinflammatory conditions included polyarthritis (n=3) and pulmonary granuloma (n=2). Death was recorded in 8 patients (15%). Conclusion: Melioidosis and C. violaceum indigenous to Southeast Asia can cause life-threatening infections in CGD patients. The high incidence of mycobacterial infections is associated with universal BCG vaccination and endemicity of tuberculosis. Such observations emphasize the role of respiratory burst as an immune defense mechanism against these pathogens. These infections are seldom reported in Caucasian cohorts, illustrating the importance of regional collaborative studies to facilitate pattern recognition and early diagnosis of primary immunodeficiencies.published_or_final_versio

Mitochondria and the regulation of free radical damage in the eye

Neuronal cell death can be determined by the overall level of reactive oxygen species (ROS) resulting from the combination of extrinsic sources and intrinsic production as a byproduct of oxidative phosphorylation. Key controllers of the intrinsic production of ROS are the mitochondrial uncoupling proteins (UCPs). By allowing a controlled leak of protons across the inner mitochondrial membrane activation of these proteins can decrease ROS and promote cell survival. In both primate models of Parkinson’s disease and mouse models of seizures, increased activity of UCP2 significantly increased neuronal cells survival. In the retina UCP2 is expressed in many neurons and glial cells, but was not detected in rod photoreceptors. Retinal ganglion cell survival following excitotoxic damage was much greater in animals overexpressing UCP2. Traditional Chinese medicines, such as an extract of Cistanche tubulosa, may provide benefit by altering mitochondrial metabolism

Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle

© 2013 Rakobowchuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33610 yr) attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, lowflow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.161.0%, POST15:4.560.6%, POST30:5. 560.7% POST45:5.960.4%, p,0.01). Conversely, low-flow mediated constriction increased (PRE: 21.360.4%, POST15: 23.360.6%, POST30: 22.560.5% POST45: 21.560.12%, p,0.01). Reactive hyperaemia was reduced throughout recovery (p,0.05). Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.British Heart Foundation (PG/08/060/25340),a Physiological Society summer studentship to SG, and a Wellcome Trust Vacation Studentship to EP

No evidence for a superior platform to develop therapeutic antibodies rapidly in response to MERS-CoV and other emerging viruses

Pascal et al. (1) generated mAbs using a platform called VelocImmune and evaluated their potency against the Middle East respiratory syndrome coronavirus (MERS-CoV) in vitro side by side with mAbs previously reported and in a mouse model developed by using VelociGene technology. The authors concluded that “Traditional approaches for development of antibodies are poorly suited to combating the emergence of novel pathogens…and that this study forms the basis for a rapid response to address the public threat resulting from emerging coronaviruses or other pathogens that pose a serious threat to human health in the future.” To support the superiority of their approach, as implied by this statement, the authors cited human mAbs previously published by three groups (2–4) and compared some of them with their own REGN3051 and REGN3048, which they found to be “more effective neutralizers than previously isolated MERS-CoV monoclonal antibodies.” They also report that their antibodies “are >1 log better inhibitors compared with other published antibodies developed with conventional approaches.” However, they did not evaluate the exceptionally potent (picomolar IC50) mAbs from one group (2) and used only published sequences, but not mAbs, provided by the investigators from the other groups (3, 4). Thus, effects that could affect potency, including those resulting from posttranslational modifications, are excluded. They also claim that the VelocImmune platform can rapidly (“within several weeks”) identify potent mAbs. However, using phage display for panning of a very large human antibody library, Ying et al. (2) identified the exceptionally potent mAb m336 in a week. According to the authors, their mouse model of MERS-CoV infection was established by replacing the mouse gene encoding a receptor targeted by the virus (DPP4) with its human counterpart, such that “this humanized DPP4 in vivo model of MERS-CoV infection recapitulates pathological sequelae that are seen in MERS-CoV infection of humans.” To our knowledge, currently, there is no animal model that can recapitulate pathology of human MERS-CoV infections in humans; therefore, it follows from this statement that their model is superior to others, which is not based on evidence. Because a full understanding of MERS pathogenesis and pathology in humans is uncertain, claiming that their model recapitulates pathological sequelae in humans, especially in the absence of morbidity and mortality, seems premature and unjustifiable. Moreover, a marmoset model (5) may be the most relevant model of MERS-CoV infection and disease. It is not cited in the text, although the reference for it is given in the bibliography. Finally, in the title of the article, the authors claim that their antibodies are fully human. However, only the germ-line antibodies inserted in the mouse genome are fully human. Because the maturation of those antibodies is in mice and the tolerance checkpoints are by mouse proteins in a mouse environment, the somatic mutations could lead to cross-reactivity of their antibodies with human tissues and immunogenicity, and therefore to undesirable adverse events and safety concerns. Taken together, the data do not provide evidence that their platform of developing mAbs, as well as models of infection and disease, is superior.published_or_final_versio

Size Effect on Failure of Pre-stretched Free-Standing Nanomembranes

Free-standing nanomembranes are two-dimensional materials with nanometer thickness but can have macroscopic lateral dimensions. We develop a fracture model to evaluate a pre-stretched free standing circular ultrathin nanomembrane and establish a relation between the energy release rate of a circumferential interface crack and the pre-strain in the membrane. Our results demonstrate that detachment cannot occur when the radius of the membrane is smaller than a critical size. This critical radius is inversely proportional to the Young’s modulus and square of the pre-strain of the membrane

Conformational changes during human P2X7 receptor activation examined by structural modelling and cysteine-based cross-linking studies

The P2X7 receptor (P2X7R) is important in mediating a range of physiological functions and pathologies associated with tissue damage and inflammation and represents an attractive therapeutic target. However, in terms of their structure-function relationships, the mammalian P2X7Rs remain poorly characterised compared to some of their other P2XR counterparts. In this study, combining cysteine-based cross-linking and whole-cell patch-clamp recording, we examined six pairs of residues (A44/I331, D48/I331, I58/F311, S60/L320, I75/P177 and K81/V304) located in different parts of the extracellular and transmembrane domains of the human P2X7R. These residues are predicted to undergo substantial movement during the transition of the receptor ion channel from the closed to the open state, predictions which are made based on structural homology models generated from the crystal structures of the zebrafish P2X4R. Our results provide evidence that among the six pairs of cysteine mutants, D48C/I133C and K81C/V304C formed disulphide bonds that impaired the channel gating to support the notion that such conformational changes, particularly those in the outer ends of the transmembrane domains, are critical for human P2X7R activation