Simulation of Bedrock Motion to Obtain PGA Values

This study is focused on producing the Peak Ground Acceleration (PGA) values for important cities in Sri Lanka, which would provide the base to develop the national annex to the Euro Code, the current guideline in designing structures. In order to find out the magnitude and the epicenter distance of a 475-year return period earthquake, an earthquake catalog was developed. To simulate the bedrock motion FLAC Software, which uses the Finite Difference approach, was used. Five 2-D FLAC models representing five cross sections of Sri Lanka were developed. Due to the lack of local data records, a dataset of seven earthquakes with the magnitude of a 475- year return period was selected from the Pacific Earthquake Engineering Research Center (PEER) database. The model was then analyzed—one cross section for each of the seven earthquakes. The resultant acceleration time histories were converted into a response spectrum, and the average spectrum for each city was obtained

Saline Water Intrusion Along the River Benthera and its Impact on Irrigation Water

Saline water intrusion is a major issue in the present era, and Benthara River has beenaffected with serious saline water intrusion along the river. The present study was conductedto identify sea water intrusion and its impact on irrigation system in the Benthera waterscheme. In addition to that study objectives were to assess salinity levels in surface waterwith precipitation and tidal waves. The study area along the river is covered with mangrovesand paddy. The research was conducted in the Ambalangoda irrigation area, Galle district inthe southern province of Sri Lanka. Study area was located in the river Bentota and the leftbank of the Benthara river basin irrigation scheme. Continuous monitoring was conductedover six months from January to June 2012. Five sampling points along the river from sea toten kilometers (10 km) upstream were identified, based on two kilometers (2 km) interval inbetweensampling points. Further, three samples from three levels that is surface, mid streamand deeper level were taken from each collecting point. Laboratory analyses of chemicalwater quality parameters were observed.The results revealed the pH and Electrical Conductivity (EC) of the river water are affectedby sea water intrusion and other anthropogenic influences. Throughout the monitoring periodEC values had not changed due to precipitation except with heavy rain. The study helped toprepare maps depicting salinity levels in the river using GIS software. It shows that most ofthe saline water goes through the river bed. Sea water intrusion occurs during afternoons ofthe time and EC values in February remained at the highest level of 32,900 micro Siemensper centimeter (μs/cm). The pH range varies from 6 to 7.5 in the morning and from 6 to 8 inthe afternoon. Electrical Conductivity values of surface water in the study area were up to32,900 μs/cm in the morning and 37,300 μs/cm in the afternoon. Chloride levels hadsignificantly differed between the collecting point near the mouth of the river and theconcluding point. Highest value of Chloride was 19,800 milligrams per liter (mg/l) in themorning and 20,692 mg/l in the afternoon.

IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination

We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery. In the current study how these cytokines act to regulate anti-viral CD8(+) T, cell avidity following HIV-1 recombinant pox viral prime-boost vaccination was investigated. Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination. Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells. Furthermore, mucosal vaccination and vaccination with the novel adjuvanted IL-13 inhibitor (i.e. IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity. Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination. Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination. These findings can be exploited to, design more efficacious vaccines not only against HIV-1, but many chronic infections where high, avidity CD8(+) T cells help protection.This work was supported by the Australian National Health and Medical Research Council project grant award 525431 (CR) and development grant award APP1000703 (CR), the Australian Centre for Hepatitis and HIV Virology EOI grant 2010/12 (CR&RJ), and Bill and Melinda Gates Foundation GCE Phase I grant OPP1015149 (CR)

MHC Class II–Alpha Chain Knockout Mice Support Increased Viral Replication That Is Independent of Their Lack of MHC Class II Cell Surface Expression and Associated Immune Function Deficiencies

MHCII molecules are heterodimeric cell surface proteins composed of an α and β chain. These molecules are almost exclusively expressed on thymic epithelium and antigen presenting cells (APCs) and play a central role in the development and function of CD4 T cells. Various MHC-II knockout mice have been generated including MHC-IIAα(-/-) (I-Aα(-/-)), MHC-IIAβ(-/-) (I-β(-/-)) and the double knockout (I-Aαxβ(-/-)). Here we report a very striking observation, namely that alphaviruses including the avirulent strain of Semliki Forest virus (aSFV), which causes asymptomatic infection in wild-type C57BL6/J (B6) mice, causes a very acute and lethal infection in I-Aα(-/-), but not in I-β(-/-) or I-Aαxβ(-/-), mice. This susceptibility to aSFV is associated with high virus titres in muscle, spleen, liver, and brain compared to B6 mice. In addition, I-Aα(-/-) mice show intact IFN-I responses in terms of IFN-I serum levels and IFN-I receptor expression and function. Radiation bone marrow chimeras of B6 mice reconstituted with I-Aα(-/-) bone marrow expressed B6 phenotype, whereas radiation chimeras of I-Aα(-/-) mice reconstituted with B6 bone marrow expressed the phenotype of high viral susceptibility. Virus replication experiments both in vivo and in vitro showed enhanced virus growth in tissues and cell cultures derived form I-Aα(-/-) compared to B6 mice. This enhanced virus replication is evident for other alpha-, flavi- and poxviruses and may be of great benefit to producers of viral vaccines. In conclusion, I-Aα(-/-) mice exhibit a striking susceptibility to virus infections independent of their defective MHC-II expression. Detailed genetic analysis will be carried out to characterise the underlining genetic defects responsible for the observed phenomenon.This work was supported by institutional research support to Prof Mullbacher laboratory at the John Curtin School of Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Reduced Interleukin-4 Receptor α Expression on CD8+ T Cells Correlates with Higher Quality Anti-Viral Immunity

With the hope of understanding how interleukin (IL)-4 and IL-13 modulated quality of anti-viral CD8(+) T cells, we evaluated the expression of receptors for these cytokines following a range of viral infections (e.g. pox viruses and influenza virus). Results clearly indicated that unlike other IL-4/IL-13 receptor subunits, IL-4 receptor α (IL-4Rα) was significantly down-regulated on anti-viral CD8(+) T cells in a cognate antigen dependent manner. The infection of gene knockout mice and wild-type (WT) mice with vaccinia virus (VV) or VV expressing IL-4 confirmed that IL-4, IL-13 and signal transducer and activator of transcription 6 (STAT6) were required to increase IL-4Rα expression on CD8(+) T cells, but not interferon (IFN)-γ. STAT6 dependent elevation of IL-4Rα expression on CD8(+) T cells was a feature of poor quality anti-viral CD8(+) T cell immunity as measured by the production of IFN-γ and tumor necrosis factor α (TNF-α) in response to VV antigen stimulation in vitro. We propose that down-regulation of IL-4Rα, but not the other IL-4/IL-13 receptor subunits, is a mechanism by which CD8(+) T cells reduce responsiveness to IL-4 and IL-13. This can improve the quality of anti-viral CD8(+) T cell immunity. Our findings have important implications in understanding anti-viral CD8(+) T cell immunity and designing effective vaccines against chronic viral infections.This work was supported by the Australian National Health and Medical Research Council project grant award 525431 (CR) and development grant award APP1000703 (CR) and the Australian Centre for Hepatitis and HIV Virology EOI grant 2010 (CR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Mucosal vaccination with a live recombinant rhinovirus followed by intradermal DNA administration elicits potent and protective HIV-specific immune responses

Published: 17 November 2016Mucosal immunity is deemed crucial to control sexual transmission of human immunodeficiency virus (HIV). Herein we report the efficacy of a mucosal HIV vaccine strategy comprising intranasal (IN) vaccination with a cocktail of live recombinant human rhinoviruses (HRVs) encoding overlapping fragments of HIV Gag and full length Tat (rHRV-Gag/Tat) followed by intradermal (ID) vaccination with DNA vaccines encoding HIV Gag and Tat (pVAX-Gag-Tat). This heterologous prime-boost strategy will be referred to hereafter as rHRV-DNA. As a control, IN vaccination with wild type (wt)-HRV-A1 followed by a single ID dose of pVAX (wt-HRV-A1/pVAX vaccination) was included. rHRV-DNA vaccination elicited superior multi-functional CD8(+)T cell responses in lymphocytes harvested from mesenteric lymph nodes and spleens, and higher titres of Tat-specific antibodies in blood and vaginal lavages, and reduced the viral load more effectively after challenge with EcoHIV, a murine HIV challenge model, in peritoneal macrophages, splenocytes and blood compared compared with wt-HRV-A1/pVAX vaccination or administration of 3 ID doses of pVAX-Gag-Tat (3X pVAX-Gag-Tat vaccination). These data provide the first evidence that a rHRV-DNA vaccination regimen can induce HIV-specific immune responses in the gut, vaginal mucosa and systemically, and supports further testing of this regimen in the development of an effective mucosally-targeted HIV-1 vaccine.Khamis Tomusange, Danushka Wijesundara, Jason Gummow, Steve Wesselingh, Andreas Suhrbier, Eric J. Gowans, Branka Grubor-Bau

Lichen floral studies on Artocarpus heterophyllus Lam. tree trunk in different eco - regions of Sri Lanka

Information on lichen flora in Sri Lanka is scarce. Therefore a study was carried out to investigatelichens growing on a tree species common to all five eco regions (Montane, Wet, Intermediate, Aridand Dry zone) of Sri Lanka. The common tree species found in all regions was Artocarpusheterophyllus Lam. (jak). Lichen flora found on bark of jak trees between 1.5 m and 2 rn above theground level was studied. Six hundred and sixty three specimens from hundred and twenty trees werestudied. Twenty five genera and thirteen families were found among them. Twenty genera werefound to be crustose and five were folioses. No fruticose lichen was found in any region. Of allidentified lichens 40% were belonged to the family Graphidaceae and it was the most frequentlyfound lichen family in all regions and the second highest (17%) was belonged to family Phyciaceae.The most frequently found genus was Graphis.Heterodermia and Pertusaria were found only in montane zone while Leptogium was found only inlowland wet zone. Thelotrema. Ocellularia. Myriotrema and Chrysothrix were found only inIntermediate zonc. Parntelia was restricted to wet zone while Dirinaria, Dimerella and Porinawere restricted to dry zone, Differences in distribution of some of these lichens can be explainedwith rain fall, temperature and humidity.

Emerging targets for developing T cell-mediated vaccines for human immunodeficiency virus (HIV)-1

Human immunodeficiency virus (HIV)-1 has infected >75 million individuals globally, and, according to the UN, is responsible for ~2.1 million new infections and 1.1 million deaths each year. Currently, there are ~37 million individuals with HIV infection and the epidemic has already resulted in 35 million deaths. Despite the advances of anti-retroviral therapy (ART), a cost-effective vaccine remains the best long-term solution to end the HIV-1 epidemic especially given that the vast majority of infected individuals live in poor socio-economic regions of the world such as Sub-Saharan Africa which limits their accessibility to ART. The modest efficacy of the RV144 Thai trial provides hope that a vaccine for HIV-1 is possible, but as markers for sterilizing immunity are unknown, the design of an effective vaccine is empirical, although broadly cross-reactive neutralizing antibodies (bNAb) that can neutralize various quasispecies of HIV-1 are considered crucial. Since HIV-1 transmission often occurs at the genito-rectal mucosa and is cell-associated, there is a need to develop vaccines that can elicit CD8+ T cell immunity with the capacity to kill virus infected cells at the genito-rectal mucosa and the gut. Here we discuss the recent progress made in developing T cell-mediated vaccines for HIV-1 and emphasize the need to elicit mucosal tissue-resident memory CD8+ T (CD8+ Trm) cells. CD8+ Trm cells will likely form a robust front-line defense against HIV-1 and eliminate transmitter/founder virus-infected cells which are responsible for propagating HIV-1 infections following transmission in vast majority of cases.From the National Health and Medical Research Council (NHMRC): grants APP1026293 (EG), APP525431 (CR), APP543139 (EG), and APP543143 (EG). From the Australian Centre for HIV and Hepatitis Virology Research, CR received an EOI gran