The Development of the Vulnerability Index (VI) using Principal Component Analysis (PCA)

Climate change elevates the rate of emergence of urban heat islands (UHIs), especially in the tropics. UHIs severely affect human comfort and health. Many studies have suggested that urban areas should be properly mitigated or planned. To cope with this, it is best to present the issue using easy-to-understand approaches to allow for better decision-making, especially during urban planning. Based on the information, adaptations and mitigation strategies can be suggested in order to reduce the impact. Hence, this research was aimed at determining the heat vulnerability index (HVI) of urban areas. This study was conducted in Malaysia in the Klang Valley, a tropical city with a complex urban morphology. Remote sensing techniques were employed to extract and derive the spatial index values for exposure, sensitivity, and adaptive capacity. A principal component analysis (PCA) was used to estimate the vulnerability as well as to generate the HVI. The most vulnerable districts were found to be Petaling (1.00), Kuala Lumpur (0.99), and Putrajaya (0.95). Kuala Lumpur had a level of exposure that was high (0.56), a level of sensitivity that was high (0.84), and capacity to adapt that was low (0.54), while Petaling had a high exposure value (0.56), very high sensitivity (1), and high adaptive capacity (0.72). A Pearson’s correlation (r) test also revealed that the variables used were highly correlated. From the preliminary findings, the vulnerability of the population to high temperatures in the Klang Valley can be identified to help develop adaptative plans that are targeted as a response to rapid warming in the future in Malaysia

Experimental study of static flow instability in subcooled flow boiling in parallel channels

Experimental data for static flow instability or flow excursion (FE) at conditions applicable to the Advanced Neutron Source Reactor are very limited. A series of FE tests with light water flowing vertically upward was completed covering a local exit heat flux range of 0.7--18 MW/m{sup 2}, exit velocity range of 2.8--28.4 m/s, exit pressure range of 0.117--1.7 MPa, and inlet temperature range of 40-- 50{degrees}C. Most of the tests were performed in a ``stiff`` (constant flow) system where the instability threshold was detected through the minimum of the pressure-drop curve. A few tests were also conducted using as ``soft`` (constant pressure drop) a system as possible to secure a true FE phenomenon (actual secondary burnout). True critical heat flux experiments under similar conditions were also conducted using a stiff system. The FE data reported in this study considerably extend the velocity range of data presently available worldwide, most of which were obtained at velocities below 10 m/s. The Saha and Zuber correlation had the best fit with the data out of the three correlations compared. However, a modification was necessary to take into account the demonstrated dependence of the St and Nu numbers on subcooling levels, especially in the low subcooling regime. Comparison of Thermal Hydraulic Test Loop (THTL) data, as well as extensive data from other investigators, led to a proposed modification to the Saha and Zuber correlation for onset of significant void, applied to FE prediction. The mean and standard deviation of the THTL data were 0.95 and 15%, respectively, when comparing the THTL data with the original Saha and Zuber correlation, and 0.93 and 10% when comparing them with the modification. Comparison with the worldwide database showed a mean and standard deviation of 1.37 and 53%, respectively, for the original Saha and Zuber correlation and 1.0 and 27% for the modification

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

Glucose Starvation Boosts Entamoeba histolytica Virulence

The unicellular parasite, Entamoeba histolytica, is exposed to numerous adverse conditions, such as nutrient deprivation, during its life cycle stages in the human host. In the present study, we examined whether the parasite virulence could be influenced by glucose starvation (GS). The migratory behaviour of the parasite and its capability to kill mammalian cells and to lyse erythrocytes is strongly enhanced following GS. In order to gain insights into the mechanism underlying the GS boosting effects on virulence, we analyzed differences in protein expression levels in control and glucose-starved trophozoites, by quantitative proteomic analysis. We observed that upstream regulatory element 3-binding protein (URE3-BP), a transcription factor that modulates E.histolytica virulence, and the lysine-rich protein 1 (KRiP1) which is induced during liver abscess development, are upregulated by GS. We also analyzed E. histolytica membrane fractions and noticed that the Gal/GalNAc lectin light subunit LgL1 is up-regulated by GS. Surprisingly, amoebapore A (Ap-A) and cysteine proteinase A5 (CP-A5), two important E. histolytica virulence factors, were strongly down-regulated by GS. While the boosting effect of GS on E. histolytica virulence was conserved in strains silenced for Ap-A and CP-A5, it was lost in LgL1 and in KRiP1 down-regulated strains. These data emphasize the unexpected role of GS in the modulation of E.histolytica virulence and the involvement of KRiP1 and Lgl1 in this phenomenon

Differential Effects of Concomitant Use of Vitamins C and E on Trophoblast Apoptosis and Autophagy between Normoxia and Hypoxia-Reoxygenation

Concomitant supplementation of vitamins C and E during pregnancy has been reportedly associated with low birth weight, the premature rupture of membranes and fetal loss or perinatal death in women at risk for preeclampsia; however, the cause is unknown. We surmise that hypoxia-reoxygenation (HR) within the intervillous space due to abnormal placentation is the mechanism and hypothesize that concomitant administration of aforementioned vitamin antioxidants detrimentally affects trophoblast cells during HR.Using villous explants, concomitant administration of 50 microM of vitamins C and E was observed to reduce apoptotic and autophagic changes in the trophoblast layer at normoxia (8% oxygen) but to cause more prominent apoptosis and autophagy during HR. Furthermore, increased levels of Bcl-2 and Bcl-xL in association with a decrease in the autophagy-related protein LC3-II were noted in cytotrophoblastic cells treated with vitamins C and E under standard culture conditions. In contrast, vitamin treatment decreased Bcl-2 and Bcl-xL as well as increased mitochondrial Bak and cytosolic LC3-II in cytotrophoblasts subjected to HR.Our results indicate that concomitant administration of vitamins C and E has differential effects on the changes of apoptosis, autophagy and the expression of Bcl-2 family of proteins in the trophoblasts between normoxia and HR. These changes may probably lead to the impairment of placental function and suboptimal growth of the fetus

Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity.

Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases. Here we evaluate the potential protective effect of downregulation of calpains. We demonstrate, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion. Furthermore, we demonstrate that, overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington's disease, improving motor signs and delaying the onset of tremors. Importantly, long-term inhibition of calpains did not result in any overt deleterious phenotypes in mice. Thus, calpain inhibition, or activation of autophagy pathways downstream of calpains, may be suitable therapeutic targets for diseases like Huntington's disease.This is the published version of the manuscript. It is available online from NPG in Cell Death and Differentiaiton here: http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd2014151a.html