Life Cycle Assessment Based Analysis of Water Bottle Designs for Defence Application

This paper presents the successful implementation of the Life Cycle Assessment (LCA) approach for the sustainable development of a defence product.  Alternative designs of this product are evaluated from the environmental burden perspective.  The products considered are water bottles used by the armed forces in places like the Siachen glacier, where the environmental factors are of great concern.  From the environmental degradation perspective, the suitability of three existing bottle types has been analysed using LCA and Life Cycle Impact Assessment (LCIA) approaches on SimaPro software for each of its components and the bottle as a whole.  Using this software, uncertainty analysis has also been carried out by conducting a Monte Carlo simulation for a reasonable confidence level.  The latest design was found to have the least environmental burden, being 82.62% less compared to the first design.  To augment the environmental performance further, the best design was again reviewed by carrying out component level analysis to identify feasible alternative materials that would be functionally equivalent but with lower environmental impact.  It suggested switching to lower impact material for the cap and cap cover for the proposed design.  With the adoption of the changed material, the environmental performance improved by 10.61 % as compared to the best design and 84.46 % compared to the earliest design.&nbsp

Nomographs for Polymeric Material Selection for Environmental Conscious Design of Industrial Products

Environmentally-conscious product design using Life Cycle Assessment (LCA) deserves the utmost attention to save and sustain our planet’s lives, flora and fauna. The choice of materials during the design stage needs to address environmental concerns from their sourcing to production and ultimately going up to the disposal stage. A good majority of industrial products are still not designed, focusing the environmental concerns. The inclusion and practice of the LCA approach during product designing are in a nascent stage not only in India but even over the rest of the world. Nowadays, polymers share a major chunk of the volume of goods produced worldwide and thus have a significant effect on the environment. The available design books or nomographs guide the selection of materials considering several criteria but not considering the related environmental issues. This paper attempts to bridge this gap only for the selection of polymeric materials by providing some easily interpretable and visually ready reckoners in the form of 3-D nomographs. These 3-D nomographs, graphical representations developed using the Solidworks software, echo the material’s Environmental Impact (EI) potential on an axis with some two material properties (e.g., tensile strength and density) on the other two axes. 3-D nomographs are suitably transformed into 2-D nomographs without the loss of any information. EIs on these nomographs were computed using SimaPro software. The potential EI of any product and the overall environmental burden due to them can be significantly reduced, and more so when they are mass-produced, by selecting the right materials using these nomographs. Such an approach will help in fulfilling long-term sustainable development goals of society and the globe

Tributyltin exposure alters cytokine levels in mouse serum

Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines

Antitumor Effect of Some 3d-Metal Complexes of N-Isonicotinoyl-N'-o-Hydroxythiobenzhydrazide

A new ligand, N-isonicotinoyl-N'-o-hydroxythiobenzhydrazide (H2Iotbh), forms complexes [Co(Iotbh)(H2O)2], [M(Iotbh)] [M Ni(II) Cu(II) and Zn(ll)] and [M(Iotbh-H)(H2O)2] [M Mn(III), Fe(III)], which were characterized by various physico-chemical techniques. DMSO solution of metal complexes was observed to inhibit the growth of tumor in vitro, whereas the ligand did not. In vivo administration of these complexes resulted in prolongation of survival of tumor-bearing mice. Tumor-bearing mice administered with the solution of metal complexes showed reversal of tumor growth associated induction of apoptosis in lymphocytes. The paper discusses the possible mechanisms and therapeutic implications of the H2lotbh and its metal complexes in tumor regression and tumor growth associated immunosuppression

Sporotrichosis in Sub-Himalayan India

Sporotrichosis is endemic in the Sub-Himalayan belt, which ranges from the northern to the north-eastern Indian subcontinent. Similar to many parts of the developing world, sporotrichosis is commonly recognized clinically in this region however consolidated epidemiological data is lacking. We report epidemiological, clinical and microbiological data from a hundred culture positive cases of sporotrichosis. Out of 305 clinically suspicious cases of sporotrichosis, a total of 100 isolates were identified as Sporothrix schenckii species complex (S. schenckii) on culture. Out of the culture proven cases 71% of the cases presented with lymphocutaneous type of lesions while 28% had fixed localized type and 1% had disseminated sporotrichosis. Presentation with lesions on hands was most frequently seen in 32% with arm (23%) and face (21%) in that sequence. The male to female ratio was 1∶1.27. Age ranged from 1 ½ years to 88 years. Mean age was 43.25 years. Disease was predominantly seen in the fourth to sixth decade of life with 58% cases between 31 and 60 years of age. Since the first report from the region there has been a steady rise in the number of cases of sporotrichosis. Seasonal trends reveal that most of the patients visited for consultation in the beginning of the year between March and April. This is the first study, from the most endemic region of the Sub-Himalayan belt, to delve into epidemiological and clinical details of such a large number of culture proven cases over a period of more than eighteen years which would help in the understanding of the local disease pattern of sporotrichosis

Correction to: Determinant Roles of Dendritic Cell-expressed Notch Delta-like and Jagged Ligands on Anti-tumor T-cell Immunity

Background: Notch intercellular communication instructs tissue-specific T-cell development and function. In this study, we explored the roles of dendritic cell (DC)-expressed Notch ligands in the regulation of T-cell effector function. Methods: We generated mice with CD11c lineage-specific deletion of Notch Delta-like ligand (Dll)1 and Jagged (Jag)2. Using these genetically-ablated mice and engineered pharmacological Notch ligand constructs, the roles of various Delta-like and Jagged ligands in the regulation of T-cell-mediated immunity were investigated. We assessed tumor growth, mouse survival, cytokine production, immunophenotyping of myeloid and lymphoid populations infiltrating the tumors, expression of checkpoint molecules and T-cell function in the experimental settings of murine lung and pancreatic tumors and cardiac allograft rejection. Correlative studies were also performed for the expression of NOTCH ligands, NOTCH receptors and PD-1 on various subsets of myeloid and lymphoid cells in tumor-infiltrating immune cells analyzed from primary human lung cancers. Results: Mice with CD11c lineage-specific deletion of Notch ligand gene Dll1, but not Jag2, exhibited accelerated growth of lung and pancreatic tumors concomitant with decreased antigen-specific CD8+ T-cell functions and effector-memory (Tem) differentiation. Increased IL-4 but decreased IFN-γ production and elevated populations of T-regulatory and myeloid-derived suppressor cells were observed in Dll1-ablated mice. Multivalent clustered DLL1-triggered Notch signaling overcame DC Dll1 deficiency and improved anti-tumor T-cell responses, whereas the pharmacological interference by monomeric soluble DLL1 construct suppressed the rejection of mouse tumors and cardiac allograft. Moreover, monomeric soluble JAG1 treatment reduced T-regulatory cells and improved anti-tumor immune responses by decreasing the expression of PD-1 on CD8+ Tem cells. A significant correlation was observed between DC-expressed Jagged and Delta-like ligands with Tem-expressed PD-1 and Notch receptors, respectively, in human lung tumor-infiltrates.Conclusion: Our data show the importance of specific expression of Notch ligands on DCs in the regulation of Tcell effector function. Thus, strategies incorporating selectively engineered Notch ligands could provide a novel approach of therapeutics for modulating immunity in various immunosuppressive conditions including cancer. Keywords: Delta-like notch ligands, Jagged, Notch receptors, Lung carcinoma, Tumor infiltrating immune cells, Heart allograft rejection, Dendritic cells, CD8 T-cells, Regulatory T-cells, Cancer immunotherap

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Advancing Health Equity and Biomedical Researcher Diversity: A New AIM-AHEAD Consortium

Despite widespread knowledge regarding racial and ethnic health disparities, little has changed over the last decades. A creative, inclusive, and competitive biomedical research workforce is the foundation for turning discovery into health for all. To date, the expertise for advancing data-driven medicine based on artificial intelligence and machine learning (AI/ML) approaches has resided in majority-oriented institutions with little demonstrated experience in engaging minority-serving institutions or communities. Lack of diversity of both data and researchers runs the risk of creating and perpetuating harmful biases in the analytical algorithms, practice, and outcomes, thus fostering continued health disparities and inequities. Thus, the National Institutes of Health recently launched an Artificial Intelligence and Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD) program. This two-year planning, assessment and capacity building program will be led by the AIM-AHEAD Coordinating Center comprised of a consortium of institutions and organizations that have a mission to serve minorities and underrepresented or underserved communities impacted by health disparities. This AIM-AHEAD research and development program seeks to illuminate underlying issues in health systems and research endeavors that need to be addressed to improve health for diverse communities