Lists all key resources and reagents

18 supplementary figures and corresponding legends

Sup Tables 5-7- Amino Acid Biochrom

This study was carried out to assess the possibility of reclamation of a closed landfill site located at Mavallipura near Bangalore, India. The existing liner system at this site had not completely prevented leachate migration to the underlying aquifers, which required management and control to avoid adverse impact on the surrounding environment. Batch leaching tests and column tests were conducted to estimate the migration rates of different contaminants through soil. The transport rates thus obtained were used as input to the fluidyn-Pollusol model to assess the leachate migration from the landfill. This model may be useful in analysing leachate migration from the landfill and its associated environmental impacts, particularly on groundwater wells and surface water ponds downstream of the site. The results indicated that landfill leachate leakage had a significant effect on the quality of surrounding water bodies.

AbstractPancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate and lacks effective therapeutics. Therefore, it is of paramount importance to identify new targets. Using multiplex data from patient tissue, three-dimensional coculturing in vitro assays, and orthotopic murine models, we identified Netrin G1 (NetG1) as a promoter of PDAC tumorigenesis. We found that NetG1+ cancer-associated fibroblasts (CAF) support PDAC survival, through a NetG1-mediated effect on glutamate/glutamine metabolism. Also, NetG1+ CAFs are intrinsically immunosuppressive and inhibit natural killer cell–mediated killing of tumor cells. These protumor functions are controlled by a signaling circuit downstream of NetG1, which is comprised of AKT/4E-BP1, p38/FRA1, vesicular glutamate transporter 1, and glutamine synthetase. Finally, blocking NetG1 with a neutralizing antibody stunts in vivo tumorigenesis, suggesting NetG1 as potential target in PDAC.Significance:This study demonstrates the feasibility of targeting a fibroblastic protein, NetG1, which can limit PDAC tumorigenesis in vivo by reverting the protumorigenic properties of CAFs. Moreover, inhibition of metabolic proteins in CAFs altered their immunosuppressive capacity, linking metabolism with immunomodulatory function.See related commentary by Sherman, p. 230.This article is highlighted in the In This Issue feature, p. 211

The safety of the environment from the industrial sludge has become a serious concern in India with the rapid increase in industrialization. The indiscriminate disposal of sludge from industries leads to the soil, groundwater and surface water pollutions. To avoid the high costs associated with the disposal of large volumes of sludge, it can be used in some building materials or can be used as fertilizer. As the accumulation of heavy metals in plants causes a threat to living beings, it has to be pretreated to remove heavy metals from the sludge to the required level before its application to soils. The heavy metals from the sludge can be reduced/separated by washing with a suitable fluid. In the present study, column leaching tests were conducted with five leaching solutions, i.e., distilled water, 0.1 N HCl, 0.1 N EDTA, 0.1 N HCl + 0.1 N EDTA and 0.1 N FeCl3 to know their removal efficiencies of heavy metal ions of Cu, Zn, Ni, Cd, Pb, Fe and Cr present in the industrial sludge. It was observed that distilled water was able to remove only few metal ions Cu, Zn and Ni in lesser quantities. 0.1 N HCl has removed Cd, Cu, Zn and Ni ions with a removal efficiency of 50%. With 0.1 N EDTA, the metal ions Cd, Cu and Zn have attained a removal efficiency of 80% and other metals have attained almost 50%. Using 0.1 N HCl + 0.1 N EDTA and 0.1 N FeCl3, all the heavy metals were leached out with removal efficiencies of (different metals) 71–98%. From this study, it was found that 0.1 N HCl + 0.1 N EDTA and 0.1 N FeCl3 were the most suitable solutions to remove heavy metals from the industrial sludge. Using the results of column leaching tests, the migration rates of different metal ions were determined which are used to design the soil washing program at the site to treat the similar sludge.

With increased population, rapid industrialization and life style changes, the characteristics and the rates of solid waste generation have gone under drastic change in India. Generally, in India, management of solid waste landfill is of major concern with respect to the existing circumstances. The illegal dumping of municipal solid waste on the outskirts of cities is creating major environmental and public health problems. Improper and unscientific waste management results in potential threats from leachate leakage with subsequent impact on environment (i.e. soil, air and waterbodies) and human being. It is therefore, important to evaluate the contamination potential threat of landfill leachate. This study assesses the potential contamination from the landfill leachate by an index called leachate pollution index (LPI) and suggestions are given the landfill sites of five major cities i.e. Bangalore, Chennai, Delhi, Navi Mumbai & Kolkata in India. The landfill leachate samples from these sites have been assessed using leachate pollution index for the implementation of appropriate leachate treatment techniques for reducing the adverse effects on the environment. The results show that the Pallikkaranai landfill site for Chennai city and Mavallipura landfill site for Bangalore city are highly deteriorating and may lead to increase in human health risk for nearby dwellings.

In the present study, column leaching tests were conducted with two leaching solutions, i.e., distilled water and 0.1N HCl + 0.1N EDTA to know their removal efficiencies of heavy metal ions of Cu, Zn, Ni, Cd, Pb, Fe and Cr present in the industrial sludge. It was observed that distilled water was a ble to remove only a few metal ions Cu, Zn, and Ni in lesser quantities. Using 0.1N HCl + 0.1N EDTA, all the heavy metals were leached out with removal efficiencies in the range of 71-98%. Using the results of column leaching tests, the migration rates of different metal ions were determined which can be used to design the soil washing programme at the site to treat the similar sludge.

The effluent treatment plant sludge is one of the major sources of contamination with toxic metals. Since the sludge contains heavy metals, it must be pretreated to reduce the contamination. The heavy metals from the sludge can be reduced/ separated by washing it with a suitable leaching solution. In the present study, the efficiencies of three leaching solutions to remove the contaminants from an industrial sludge were studied and the leaching process was modeled. The leaching solutions used are 0.1 N HCl, 0.1 N EDTA and 0.1 N FeCl3. The efficiencies of leaching solutions were assessed by conducting column leaching experiments on the sludge and the migration rates of heavy metal ions of Cu, Zn, Ni, Cd, Pb, Fe and Cr present in the sludge were estimated. These migration rates are useful to estimate the quantity of leaching solution required at the site to achieve the required levels of concentrations in the sludge.

Pancreatic ductal adenocarcinoma (PDAC) is predicted to soon become the second killer cancer in the USA. One of the hallmarks of PDAC is desmoplasia, which consists of an expansion in activated stellate cells, known as cancer associated fibroblasts (CAFs), and remodeling of their extracellular matrix. Desmoplasia is a major culprit for the unique PDAC microenvironment, which both collapses blood vessels restricting nutrients and fosters immunosuppression. Crosstalk between CAFs, PDAC, and immune cells, within this microenvironment, is not fully understood. To study the functions of CAFs on PDAC development, we first performed a microarray comparing patient matched normal pancreatic stellate cells and CAFs cultured using our stromal 3D system. We identified proteins upregulated in CAFs that have not been previously implicated in desmoplasia. To understand the functional role of these proteins, CRISPR/Cas9 mediated deletion of target proteins was undertaken and cells were subjected to a number of co-culture assays, with PDAC cells and NK cells. Assays consisted of material transfer, cell engagement, proliferation, survival, NK cell activation and PDAC killing. Syngeneic/orthotopic in vivo models, RNAseq analyzes and quantitative multi-plex microscopy, on pathological samples, were also used. We uncovered the ectopic expressions of NetrinG1 (NG1), a neural pre-synaptic protein, in CAFs, and of NG1’s post-synaptic binding partner, NGL1, in PDAC cells. Using our 3D system, we observed that heterotypic CAF-to-PDAC interactions, via NG1/NGL1 engagement, are critical for providing survival advantages to nutrient deprived PDAC cells and for CAFs to protect PDAC from NK cell-driven elimination. Mechanistically, we uncovered that PDAC starvation is overcome by NG1 expressing CAFs that provide nutrition via material transfer. Further, knockout of NG1, in CAFs, significantly reduced the production of immunosuppressive cytokines, such as IL-6, IL-8, and TGF-β. Moreover, loss of NG1 from CAFs resulted in anti-tumor NK cell activation. Unexpectedly, we observed a link between glutamate metabolism in CAFs and the inactivation of anti-tumor NK cells, and this was dependent on CAFs’ NG1 expression. These results were confirmed in an orthotopic PDAC mouse model in which ablation of NGL1, in syngeneic mouse PDAC cells, significantly halted tumor growth. RNAseq comparing CON or NG1+ CAFs vs. knockout NG1- CAFs rendered changes in neural, metabolic and fibrous signature pathways. Translationally, we saw clear expression of stromal NG1 only in PDAC affected pancreata. Overall, this study identifies two novel targets for PDAC; a cancer that lacks effective therapies. Inhibition of the NG1/NGL1 axis, constitutes a potential future therapeutic approach, as it alters CAF mediated metabolism and reverts immunosuppression, stunting PDAC growth in vitro and in vivo. Citation Format: Ralph Francescone, Débora Barbosa Vendramini-Costa, Janusz Franco-Barraza, Jessica Wagner, Alex Muir, Linara Gabitova, Tatiana Pazina, Tiffany Luong, Neelima Shah, Dustin Rollins, Ruchi Malik, Sapna Gupta, Roshan Thapa, Diana Restifo, Allison Lau, Yan Zhou, Kathy Q. Cai, Harvey Harvey Hensley, Emmanuelle Nicolas, Warren D. Kruger, Karthik Devarajan, Siddharth Balachandran, Wafik S. El-Deiry, Matthew Vander Heiden, Kerry Campbell, Igor Astsaturov, Edna Cukierman. NG1/NGL1 engagement supports PDAC development via CAF to PDAC nutrition and CAF-regulated immunosuppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2038.

It is predicted that pancreatic ductal adenocarcinoma (PDAC) will become the second most lethal cancer in the US by 2030. PDAC includes a fibrous-like stroma, desmoplasia, encompassing most of the tumor mass, which is produced by cancer-associated fibroblasts (CAFs) and includes their cell-derived extracellular matrices (CDMs). Since elimination of desmoplasia has proven detrimental to patients, CDM reprogramming, as opposed to stromal ablation, is therapeutically desirable. Hence, efforts are being made to harness desmoplasia's anti-tumor functions. We conducted biomechanical manipulations, using variations of pathological and physiological substrates in vitro, to culture patient-harvested CAFs and generate CDMs that restrict PDAC growth and spread. We posited that extrinsic modulation of the environment, via substrate rigidity, influences CAF's cell-intrinsic forces affecting CDM production. Substrates used were polyacrylamide gels of physiological (~1.5 kPa) or pathological (~7 kPa) stiffnesses. Results showed that physiological substrates influenced CAFs to generate CDMs similar to normal/control fibroblasts. We found CDMs to be softer than the corresponding underlying substrates, and CDM fiber anisotropy (i.e., alignment) to be biphasic and informed via substrate-imparted morphological CAF aspect ratios. The biphasic nature of CDM fiber anisotropy was mathematically modeled and proposed a correlation between CAF aspect ratios and CDM alignment; regulated by extrinsic and intrinsic forces to conserve minimal free energy. Biomechanical manipulation of CDMs, generated on physiologically soft substrates, leads to reduction in nuclear translocation of pERK1/2 in KRAS mutated pancreatic cells. ERK2 was found essential for CDM-regulated tumor cell spread. In vitro findings correlated with in vivo observations; nuclear pERK1/2 is significantly high in human PDAC samples. The study suggests that altering underlying substrates enable CAFs to remodel CDMs and restrict pancreatic cancer cell spread in an ERK2 dependent manner.

Only about 8 percent of patients with pancreatic ductal adenocarcinoma, PDAC, live up to 5 years following diagnosis; by 2020 PDAC will become the second most lethal cancer in the United States. PDAC includes an anisotropic fibrous-like stroma, desmoplasia, encompassing most of the tumor mass. Desmoplasia is produced by cancer-associated fibroblasts, CAFs, and their cell-derived extracellular matrices, CDMs. Since elimination of CAFs is detrimental to patients, CDM reprogramming, as opposed to desmoplasia ablation, is therapeutically desirable. In this study we used a human mimetic three-dimensional CAF producing CDM system and proceeded to study its dynamic architectural modifications, following underlying substrate stiffness alterations, using digital imaging analyses, atomic force microscopy, mathematical modeling, cell biology, biochemistry and human tissue quantitative simultaneous multiplex immunofluorescence. Results suggested that the architecture of CDMs can be manipulated to render a tumor-suppressive microenvironment. We posit that perhaps treatments that could reprogram desmoplasia to become tumor-restrictive or that could target tumoral ERK2 might provide future new means for treating PDAC patients.

This paper discusses the effects of a potential leachate leakage from a municipal solid waste landfill, situated at Mavallipura, Bangalore, India, on the surrounding water bodies. The landfill area is spread over an area of about 100 acres that began accepting waste from 2005. MSW was deposited in non-engineered manner that has resulting in steep and unstable slopes, leachate accumulation within the MSW mass, and leachate runoff into nearby water bodies such as ponds and open wells. The current study investigates the physicochemical characterization of landfill leachate and nearby water bodies. The batch leach tests were conducted to know the heavy metal concentrations in the contaminated soil. A series of column tests were also conducted to estimate the migration rates of different contaminants through the soil. Furthermore, these transport parameters were considered as input for fluidyn-POLLUSOL model to estimate the migration of leachate from the landfill site to the surrounding water bodies.

Disposal of the waste material is major concern for industries. Red mud is an example of industrial waste having no effective waste recovery. About 1 ton of alumina is produced from 3 tons of bauxite and about 1 ton aluminium is produced from 2 tons of alumina. Depending on the raw material processed, 1-1.5 tons of red mud is generated per ton of alumina produced. The cost of red mud disposal is expensive, accounting for about 2% of the alumina price. Waste foundry sand is another industrial waste produced during No-bake sand system. On an average 1 ton of casting produced by No-bake process generates about 1.5-2 tons of waste foundry sand. In the present work, the waste material of foundry together with red mud is used as an aggregate to develop certain value added product by mechanical and thermal treatments. An attempt has been made in this work to use both these products together with a view to study their characteristics in the as-received conditions followed by experimentation based on the statistical principle governing Taguchi and ANOVA techniques. This work assesses the behavior of a predetermined shaped compact while sintering with optimization of the process parameters. The study revealed that the temperature and time of sintering have a significant effect on the compressive strength, water absorption and apparent porosity .Sintered product has a pH of 8.17 which is very close to the neutral value. Index Terms Red mud, Foundry waste, Taguchi and ANOVA

Desmoplasia, a fibrotic mass including cancer-associated fibroblasts (CAFs) and self-sustaining extracellular matrix (D-ECM), is a puzzling feature of pancreatic ductal adenocarcinoma (PDACs). Conflicting studies have identified tumor-restricting and tumor-promoting roles of PDAC-associated desmoplasia, suggesting that individual CAF/D-ECM protein constituents have distinguishable tumorigenic and tumor-repressive functions. Using 3D culture of normal pancreatic versus PDAC-associated human fibroblasts, we identified a CAF/D-ECM phenotype that correlates with improved patient outcomes, and that includes CAFs enriched in plasma membrane-localized, active α5β1-integrin. Mechanistically, we established that TGFβ is required for D-ECM production but dispensable for D-ECM-induced naïve fibroblast-to-CAF activation, which depends on αvβ5-integrin redistribution of pFAK-independent active α5β1-integrin to assorted endosomes. Importantly, the development of a simultaneous multi-channel immunofluorescence approach and new algorithms for computational batch-analysis and their application to a human PDAC panel, indicated that stromal localization and levels of active SMAD2/3 and α5β1-integrin distinguish patient-protective from patient-detrimental desmoplasia and foretell tumor recurrences, suggesting a useful new prognostic tool.

Plastics are synthetic product produced from a wide range of polymers such as polyethylene, polyvinyl chloride, nylon etc. The property that makes it so ubiquitous to use is that it can be moulded to the desired shape and once is set can serve the desired purpose. Plastics are lightweight, inexpensive and durable materials, which find its use in a wide range of applications. The easy availability of plastics has led to its exploitation and careless use. This excessive usage caused the accumulation of huge amount of plastic waste into the environment. Plastics have a very high life in the environment and do not disintegrate through the natural process in the environment. So, the plastic disposal without any effective technique accumulates the waste into the environment certainly causing pollution. Researchers have shown that since plastics are a product of petroleum they have the efficiency to be used for fuel production which will solve the problem of plastic disposal and the rising fuel crisis. The review of past studies related to the fuel production from waste plastics, plastic waste disposal techniques, sources of alternative fuel and waste management technologies aims to find out the best technique for waste plastic disposal and a source of alternative fuel using the discarded plastics as feedstock. This would solve the problem of plastic waste disposal and fuel crisis in a

© 2017, IRJET | Impact Factor value: 5.181 | ISO 9001:2008 Certified Journal | Page 2550 A critical review of the causes of cost overrun in construction industries in developing countries Shambalid Ahady 1*, Sakshi Gupta2, R.K.Malik3 1Post Graduate Scholar , Department of Civil Engineering, Amity School of Engineering &Technology, Amity University, Haryana, India 2AssistantProfessor, Department of Civil Engineering, Amity School of Engineering &Technology, Amity University, Haryana, India 3 Professor, Department of Civil Engineering, Amity School of Engineering &Technology, Amity University, Haryana, India *Corresponding Author: s.ahady@gmail.com ---------------------------------------------------------------------***--------------------------------------------------------------------Abstract The success of any construction projects is