Development of a Partial Proportional Odds Model for Pedestrian Injury Severity at Intersections

Pedestrian injury in crashes at intersections often results from complex interaction among various factors. The factor identification is a critical task for understanding the causes and improving the pedestrian safety. A total of 2,614 crash records at signalized and non-signalized intersections were applied. A Partial Proportional Odds (PPO) model was developed to examine the factors influencing Pedestrian Injury Severity (PIS) because it can accommodate the ordered response nature of injury severity. An elasticity analysis was conducted to quantify the marginal effects of contributing factors on the likelihood of PIS. For signalized intersections, seven explanatory variables significantly affect the likelihood of PIS, in which five explanatory variables violate the Proportional Odds Assumption (POA). Local driver, truck, holiday, clear weather, and hit-and-run lead to higher likelihood of severer PIS. For non-signalized intersections, six explanatory variables were found significant to the PIS, in which three explanatory variables violate the POA. Young and adult drivers, senior pedestrian, bus/van, divided road, holiday, and darkness tend to increase the likelihood of severer PIS. The vehicles of large size and heavy weight (e.g. truck, bus/van) are significant factors to the PIS at both signalized and non-signalized intersections. The proposed PPO model has demonstrated its effectiveness in identifying the effects of contributing factors on the PIS.</p

Modeling study on the flow, heat transfer and energy conversion characteristics of low-power arc-heated hydrogen/nitrogen thrusters

A modeling study is conducted to investigate the effect of hydrogen content in propellants on the plasma flow, heat transfer and energy conversion characteristics of low-power (kW class) arc-heated hydrogen/nitrogen thrusters (arcjets). 1:0 (pure hydrogen), 3:1 (to simulate decomposed ammonia), 2:1 (to simulate decomposed hydrazine) and 0:1 (pure nitrogen) hydrogen/nitrogen mixtures are chosen as the propellants. Both the gas flow region inside the thruster nozzle and the anode-nozzle wall are included in the computational domain in order to better treat the conjugate heat transfer between the gas flow region and the solid wall region. The axial variations of the enthalpy flux, kinetic energy flux, directed kinetic-energy flux, and momentum flux, all normalized to the mass flow rate of the propellant, are used to investigate the energy conversion process inside the thruster nozzle. The modeling results show that the values of the arc voltage, the gas axial-velocity at the thruster exit, and the specific impulse of the arcjet thruster all increase with increasing hydrogen content in the propellant, but the gas temperature at the nitrogen thruster exit is significantly higher than that for other three propellants. The flow, heat transfer, and energy conversion processes taking place in the thruster nozzle have some common features for all the four propellants. The propellant is heated mainly in the near-cathode and constrictor region, accompanied with a rapid increase of the enthalpy flux, and after achieving its maximum value, the enthalpy flux decreases appreciably due to the conversion of gas internal energy into its kinetic energy in the divergent segment of the thruster nozzle. The kinetic energy flux, directed kinetic energy flux and momentum flux also increase at first due to the arc heating and the thermodynamic expansion, assume their maximum inside the nozzle and then decrease gradually as the propellant flows toward the thruster exit. It is found that a large energy loss (31-52%) occurs in the thruster nozzle due to the heat transfer to the nozzle wall and too long nozzle is not necessary. Modeling results for the NASA 1-kW class arcjet thruster with hydrogen or decomposed hydrazine as the propellant are found to compare favorably with available experimental data

Noninjection Synthesis of CdS and Alloyed CdSxSe1−xNanocrystals Without Nucleation Initiators

CdS and alloyed CdSxSe1−x nanocrystals were prepared by a simple noninjection method without nucleation initiators. Oleic acid (OA) was used to stabilize the growth of the CdS nanocrystals. The size of the CdS nanocrystals can be tuned by changing the OA/Cd molar ratios. On the basis of the successful synthesis of CdS nanocrystals, alloyed CdSxSe1−x nanocrystals can also be prepared by simply replacing certain amount of S precursor with equal amount of Se precursor, verified by TEM, XRD, EDX as well as UV–Vis absorption analysis. The optical properties of the alloyed CdSxSe1−x nanocrystals can be tuned by adjusting the S/Se feed molar ratios. This synthetic approach developed is highly reproducible and can be readily scaled up for potential industrial production

Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP

Graphene Photonics and Optoelectronics

The richness of optical and electronic properties of graphene attracts enormous interest. Graphene has high mobility and optical transparency, in addition to flexibility, robustness and environmental stability. So far, the main focus has been on fundamental physics and electronic devices. However, we believe its true potential to be in photonics and optoelectronics, where the combination of its unique optical and electronic properties can be fully exploited, even in the absence of a bandgap, and the linear dispersion of the Dirac electrons enables ultra-wide-band tunability. The rise of graphene in photonics and optoelectronics is shown by several recent results, ranging from solar cells and light emitting devices, to touch screens, photodetectors and ultrafast lasers. Here we review the state of the art in this emerging field.Comment: Review Nature Photonics, in pres

Significance of the Balance between Regulatory T (Treg) and T Helper 17 (Th17) Cells during Hepatitis B Virus Related Liver Fibrosis

<div><h3>Background</h3><p>Hepatitis B virus-related liver fibrosis (HBV-LF) always progresses from inflammation to fibrosis. However, the relationship between these two pathological conditions is not fully understood. Here, it is postulated that the balance between regulatory T (Treg) cells and T helper 17 (Th17) cells as an indicator of inflammation may predict fibrosis progression of HBV-LF.</p> <h3>Methodology/Principal Findings</h3><p>The frequencies and phenotypes of peripheral Treg and Th17 cells of seventy-seven HBeAg-positive chronic hepatitis B (CHB) patients who underwent liver biopsies and thirty healthy controls were determined by flow cytometry. In the periphery of CHB patients, both Treg and Th17 frequencies were significantly increased and correlated, and a lower Treg/Th17 ratio always indicated more liver injury and fibrosis progression. To investigate exact effects of Treg and Th17 cells during HBV-LF, a series of <em>in vitro</em> experiments were performed using purified CD4⁺, CD4⁺CD25⁺, or CD4⁺CD25⁻ cells from the periphery, primary human hepatic stellate cells (HSCs) isolated from healthy liver specimens, human recombinant interleukin (IL)-17 cytokine, anti-IL-17 antibody and HBcAg. In response to HBcAg, CD4⁺CD25⁺ cells significantly inhibited cell proliferation and cytokine production (especially IL-17 and IL-22) by CD4⁺CD25⁻ cells in cell-contact and dose-dependent manners. In addition, CD4⁺ cells from CHB patients, compared to those from HC subjects, dramatically promoted proliferation and activation of human HSCs. Moreover, in a dramatically dose-dependent manner, CD4⁺CD25⁺ cells from CHB patients inhibited, whereas recombinant IL-17 response promoted the proliferation and activation of HSCs. Finally, <em>in vivo</em> evidence about effects of Treg/Th17 balance during liver fibrosis was obtained in concanavalin A-induced mouse fibrosis models via depletion of CD25⁺ or IL-17⁺ cells, and it’s observed that CD25 depletion promoted, whereas IL-17 depletion, alleviated liver injury and fibrosis progression.</p> <h3>Conclusions/Significance</h3><p>The Treg/Th17 balance might influence fibrosis progression in HBV-LF via increase of liver injury and promotion of HSCs activation.</p> </div

Variants of the Matrix Metalloproteinase-2 but not the Matrix Metalloproteinase-9 genes significantly influence functional outcome after stroke

<p>Abstract</p> <p>Background</p> <p>Multiple lines of evidence suggest that genetic factors contribute to stroke recovery. The matrix metalloproteinases -2 (MMP-2) and -9 (MMP-9) are modulators of extracellular matrix components, with important regulatory functions in the Central Nervous System (CNS). Shortly after stroke, MMP-2 and MMP-9 have mainly damaging effects for brain tissue. However, MMPs also have a beneficial activity in angiogenesis and neurovascular remodelling during the delayed neuroinflammatory response phase, thus possibly contributing to stroke functional recovery.</p> <p>Methods</p> <p>In the present study, the role of <it>MMP-2 </it>and <it>MMP-9 </it>genetic variants in stroke recovery was investigated in 546 stroke patients. Functional outcome was assessed three months after a stroke episode using the modified Rankin Scale (mRS), and patients were classified in two groups: good recovery (mRS ≤ 1) or poor recovery (mRS>1). Haplotype tagging single nucleotide polymorphisms (SNPs) in the <it>MMP-2 </it>(N = 21) and <it>MMP-9 </it>(N = 4) genes were genotyped and tested for association with stroke outcome, adjusting for significant non-genetic clinical variables.</p> <p>Results</p> <p>Six SNPs in the <it>MMP-2 </it>gene were significantly associated with stroke outcome (0.0018<<it>P </it>< 0.0415), two of which survived the Bonferroni correction for multiple testing. In the subset of ischemic stroke patients, association of five of these SNPs remained positive (0.0042<<it>P </it>< 0.0306). No significant associations were found for the <it>MMP-9 </it>gene.</p> <p>Conclusions</p> <p>The results presented strongly indicate that <it>MMP-2 </it>genetic variants are an important mediator of functional outcome after stroke.</p

Unregulated miR-96 Induces Cell Proliferation in Human Breast Cancer by Downregulating Transcriptional Factor FOXO3a

FOXO transcription factors are key tumor suppressors in mammalian cells. Until now, suppression of FOXOs in cancer cells was thought to be mainly due to activation of multiple onco-kinases by a phosphorylation-ubiquitylation-mediated cascade. Therefore, it was speculated that inhibition of FOXO proteins would naturally occur through a multiple step post-translational process. However, whether cancer cells may downregulate FOXO protein via an alternative regulatory mechanism is unclear. In the current study, we report that expression of miR-96 was markedly upregulated in breast cancer cells and breast cancer tissues compared with normal breast epithelial cells (NBEC) and normal breast tissues. Ectopic expression of miR-96 induced the proliferation and anchorage-independent growth of breast cancer cells, while inhibition of miR-96 reduced this effect. Furthermore, upregulation of miR-96 in breast cancer cells resulted in modulation of their entry into the G1/S transitional phase, which was caused by downregulation of cyclin-dependent kinase (CDK) inhibitors, p27Kip1 and p21Cip1, and upregulation of the cell-cycle regulator cyclin D1. Moreover, we demonstrated that miR-96 downregulated FOXO3a expression by directly targeting the FOXO3a 3′-untranslated region. Taken together, our results suggest that miR-96 may play an important role in promoting proliferation of human breast cancer cells and present a novel mechanism of miRNA-mediated direct suppression of FOXO3a expression in cancer cells

The Extended Cleavage Specificity of Human Thrombin

Thrombin is one of the most extensively studied of all proteases. Its central role in the coagulation cascade as well as several other areas has been thoroughly documented. Despite this, its consensus cleavage site has never been determined in detail. Here we have determined its extended substrate recognition profile using phage-display technology. The consensus recognition sequence was identified as, P2-Pro, P1-Arg, P1′-Ser/Ala/Gly/Thr, P2′-not acidic and P3′-Arg. Our analysis also identifies an important role for a P3′-arginine in thrombin substrates lacking a P2-proline. In order to study kinetics of this cooperative or additive effect we developed a system for insertion of various pre-selected cleavable sequences in a linker region between two thioredoxin molecules. Using this system we show that mutations of P2-Pro and P3′-Arg lead to an approximate 20-fold and 14-fold reduction, respectively in the rate of cleavage. Mutating both Pro and Arg results in a drop in cleavage of 200–400 times, which highlights the importance of these two positions for maximal substrate cleavage. Interestingly, no natural substrates display the obtained consensus sequence but represent sequences that show only 1–30% of the optimal cleavage rate for thrombin. This clearly indicates that maximal cleavage, excluding the help of exosite interactions, is not always desired, which may instead cause problems with dysregulated coagulation. It is likely exosite cooperativity has a central role in determining the specificity and rate of cleavage of many of these in vivo substrates. Major effects on cleavage efficiency were also observed for residues as far away as 4 amino acids from the cleavage site. Insertion of an aspartic acid in position P4 resulted in a drop in cleavage by a factor of almost 20 times