3D Localisation of Target using Elevation Angle Algorithm with the use of Ground Radars

A new novel method based on elevation angle algorithm (EAA) is proposed in this paper, to obtain 3D position of target using range and azimuth measurements of two ground 2D radars. The EAA estimates optimal target elevation angle wrt contributing radar by solving a non-linear optimisation problem using Levenberg-Marquardt method in geo-centric frame such as earth-centred-earth-fixed. The target position in geodetic frame (WGS84) is then obtained using slant range, azimuth and estimated elevation angle. The proposed method is evaluated using simulated but realistic radar data and accuracy of estimated position is found to be comparable with true position (error within acceptable limit). The method is also evaluated with real data from actual ground 2D radars and estimated target position is found to be comparable with reference navigation data (GPS) on-board of target. For each radar, corresponding Extended Kalman filter (EKF) is used to handle noisy, asynchronous measurements and to provide estimated range and azimuth at common reference time for altitude estimation using proposed EAA method. In case of real data, the estimated altitude is found to be comparable GPS altitude with error less than 5 % of true altitude. From the study, it is found that EAA is suitable to estimate target position using measurements from only two contributing asynchronous 2D radars in real-time as compared to some other techniques such triangulation and Trilateration where at-least three radars are required to get the position of target. This method can be useful to utilise network of vintage long range 2D radars to determine target position and to fill the gap wherever/whenever target is out of detection range of 3D radars. In addition, EAA method is compared with commonly used methodology such range only localisation and results are presented

Computational Exploration of Flash-Boiling Internal Flow and Near-Nozzle Spray

Gasoline engines operating under the principle of direct injection are susceptible to flash-boiling due to superheated nature of the fuel and the sub-atmospheric in-cylinder pressures during injection. A review of the literature on flash-boiling sprays shows that a majority of the studies have focused on the far-field regions of the spray, with limited attention given to understanding the influences of the injector geometry and the near-nozzle regions of the spray. Modeling the internal nozzle flow and the primary atomization, on which the far-field spray depends, is a challenge. This thesis, therefore, is aimed at understanding the complex flow through a fuel injector nozzle and the nature of the spray in the near-nozzle region, with the help of computer simulations under flash-boiling and non-flash-boiling conditions. In the current study, the simulations were performed using an in-house Eulerian CFD solver called HRMFoam. Improvements to the solver\u27s near-nozzle spray modeling capability are discussed. These improvements include the implementation of a liquid-gas interface-area-density transport equation to model the primary atomization process. The simulations of direct injection of gasoline and gasoline-like sprays were performed on single-hole and multi-hole injectors, for a wide range of operating conditions. Spray characteristics such as the nozzle\u27s coefficient of discharge and the mean droplet diameter in the dense region of the spray were seen to be captured adequately well with the help of a 2D axi-symmetry assumption in the case of single-hole injectors. A novel approach to identify the near-nozzle spray plume boundary in CFD simulations is presented and validated against experimental measurements for a single-hole asymmetric injector. Case studies on single-hole asymmetric injectors revealed a direct correlation between the drill angle of the nozzle and near-nozzle spray plume angle. A hypothesis of the similarity between a stepped-hole two-phase nozzle and a conventional single-phase converging-diverging nozzle is presented. Furthermore, it was observed that flash-boiling jets behave as underexpanded jets, and therefore, are wider. Whereas, non-flash-boiling behave as overexpanded jets, and thus are narrower. Through the case studies on multi-hole injectors, the collapse of the spray or lack thereof was qualitatively and quantitatively characterized. In this process, a resemblance between the experimentally and computationally identified spray collapse mechanism was established. The application of LES modeling to internal and near-nozzle GDI sprays was explored in a pilot study, and the results were qualitatively validated against the experimentally available near-nozzle X-ray radiography measurements. Finally, in another pilot study, an attempt to model the interphase slip velocity is discussed

Synthesis and anti–microbial activity of 1,2,3–triazole tethered nitroguiacol ethers

Nitro aromatic/nitrophenols have been widely distributed in nature and are mostly isolated from marine microorganisms and had shown a broad spectrum of anti–microbial activities against a wide range of microbial pathogens. The objective of the present work is to Synthesize some new 1,2,3–triazole tethered nitroguiacol ethers and evaluated of their anti–bacterial and anti–fungal activities. A focused library of 1,2,3-triazole tethered nitroguiacol ethers were prepared by employing Cu (I) catalyzed click chemistry reaction and evaluated for their antimicrobial activities by broth microdilution method. Among the tested compounds, compounds 8e, 8f, 8g, and 8i exhibited broad–spectrum activity against selected pathogenic strains, with the MIC of 8 µg/mL for gram–positive bacteria (Staphylococcus aureus), 16 µg/mL for Pseudomonas aeruginosa (gram–negative bacteria), and Candida species, respectively. Future investigations with this class of compounds may lead to the development of potential candidates for antimicrobial drug discovery.Â

Somatic mutations in exocrine pancreatic tumors: association with patient survival.

KRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were detected in 134 tumors, with 131 in codon 12 and only 3 in codon 61. The GGT>GAT (G12D) was the most frequent mutation and was present in 60% (80/134). Deletions and mutations in CDKN2A were detected in 43 tumors. Analysis showed that KRAS mutations were associated with reduced patient survival in both malignant exocrine and ductal adenocarcinomas (PDAC). Patients with PDACs that had KRAS mutations showed a median survival of 17 months compared to 30 months for those without mutations (log-rank P = 0.07) with a multivariate hazard ratio (HR) of 2.19 (95%CI 1.09-4.42). The patients with G12D mutation showed a median survival of 16 months (log-rank-test P = 0.03) and an associated multivariate HR 2.42 (95%CI 1.14-2.67). Although, the association of survival in PDAC patients with CDKN2A aberrations in tumors was not statistically significant, the sub-group of patients with concomitant KRAS mutations and CDKN2A alterations in tumors were associated with a median survival of 13.5 months compared to 22 months without mutation (log-rank-test P = 0.02) and a corresponding HR of 3.07 (95%CI 1.33-7.10). Our results are indicative of an association between mutational status and survival in PDAC patients, which if confirmed in subsequent studies can have potential clinical application

Evidence for Regulated Interleukin-4 Expression in Chondrocyte-Scaffolds under In Vitro Inflammatory Conditions

OBJECTIVE: To elucidate the anti-inflammatory and anabolic effects of regulated expression of IL-4 in chondrocyte-scaffolds under in vitro inflammatory conditions. METHODS: Mature articular chondrocytes from dogs (n = 3) were conditioned through transient transfection using pcDNA3.1.cIL-4 (constitutive) or pCOX-2.cIL-4 (cytokine-responsive) plasmids. Conditioned cells were seeded in alginate microspheres and rat-tail collagen type I matrix (CaReS®) to generate two types of tissue-engineered 3-dimensional scaffolds. Inflammatory arthritis was simulated in the packed chondrocytes through exogenous addition of recombinant canine (rc) IL-1β (100 ng/ml) plus rcTNFα (50 ng/ml) in culture media for 96 hours. Harvested cells and culture media were analyzed by various assays to monitor the anti-inflammatory and regenerative (anabolic) properties of cIL-4. RESULTS: cIL-4 was expressed from COX-2 promoter exclusively on the addition of rcIL-1β and rcTNFα while its expression from CMV promoter was constitutive. The expressed cIL-4 downregulated the mRNA expression of IL-1β, TNFα, IL-6, iNOS and COX-2 in the cells and inhibited the production of NO and PGE(2) in culture media. At the same time, it up-regulated the expression of IGF-1, IL-1ra, COL2a1 and aggrecan in conditioned chondrocytes in both scaffolds along with a diminished release of total collagen and sGAG into the culture media. An increased amount of cIL-4 protein was detected both in chondrocyte cell lysate and in concentrated culture media. Neutralizing anti-cIL-4 antibody assay confirmed that the anti-inflammatory and regenerative effects seen are exclusively driven by cIL-4. There was a restricted expression of IL-4 under COX-2 promoter possibly due to negative feedback loop while it was over-expressed under CMV promoter (undesirable). Furthermore, the anti-inflammatory /anabolic outcomes from both scaffolds were reproducible and the therapeutic effects of cIL-4 were both scaffold- and promoter-independent. CONCLUSIONS: Regulated expression of therapeutic candidate gene(s) coupled with suitable scaffold(s) could potentially serve as a useful tissue-engineering tool to devise future treatment strategies for osteoarthritis

Smad7 induces hepatic metastasis in colorectal cancer

Although Smad signalling is known to play a tumour suppressor role, it has been shown to play a prometastatic function also in breast cancer and melanoma metastasis to bone. In contrast, mutation or reduced level of Smad4 in colorectal cancer is directly correlated to poor survival and increased metastasis. However, the functional role of Smad signalling in metastasis of colorectal cancer has not been elucidated. We previously reported that overexpression of Smad7 in colon adenocarcinoma (FET) cells induces tumorigenicity by blocking TGF-β-induced growth inhibition and apoptosis. Here, we have observed that abrogation of Smad signalling by Smad7 induces liver metastasis in a splenic injection model. Polymerase chain reaction with genomic DNA from liver metastases indicates that cells expressing Smad7 migrated to the liver. Increased expression of TGF-β type II receptor in liver metastases is associated with phosphorylation and nuclear accumulation of Smad2. Immunohistochemical analyses have suggested poorly differentiated spindle cell morphology and higher cell proliferation in Smad7-induced liver metastases. Interestingly, we have observed increased expression and junctional staining of Claudin-1, Claudin-4 and E-cadherin in liver metastases. Therefore, this report demonstrates, for the first time, that blockade of TGF-β/Smad pathway in colon cancer cells induces metastasis, thus supporting an important role of Smad signalling in inhibiting colon cancer metastasis

Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells

Hepatocellular carcinoma (HCC) usually arises from hepatic fibrosis caused by chronic inflammation. In chronic liver damage, hepatic stellate cells undergo progressive activation to myofibroblasts (MFB), which are important extracellular-matrix-producing mesenchymal cells. Concomitantly, perturbation of transforming growth factor (TGF)-β signaling by pro-inflammatory cytokines in the epithelial cells of the liver (hepatocytes) promotes both fibrogenesis and carcinogenesis (fibro-carcinogenesis). Insights into fibro-carcinogenic effects on chronically damaged hepatocytes have come from recent detailed analyses of the TGF-β signaling process. Smad proteins, which convey signals from TGF-β receptors to the nucleus, have intermediate linker regions between conserved Mad homology (MH) 1 and MH2 domains. TGF-β type I receptor and pro-inflammatory cytokine-activated kinases differentially phosphorylate Smad2 and Smad3 to create phosphoisoforms phosphorylated at the COOH-terminal, linker, or both (L/C) regions. After acute liver injury, TGF-β-mediated pSmad3C signaling terminates hepatocytic proliferation induced by the pro-inflammatory cytokine-mediated mitogenic pSmad3L pathway; TGF-β and pro-inflammatory cytokines synergistically enhance collagen synthesis by activated hepatic stellate cells via pSmad2L/C and pSmad3L/C pathways. During chronic liver disease progression, pre-neoplastic hepatocytes persistently affected by TGF-β together with pro-inflammatory cytokines come to exhibit the same carcinogenic (mitogenic) pSmad3L and fibrogenic pSmad2L/C signaling as do MFB, thereby accelerating liver fibrosis while increasing risk of HCC. This review of Smad phosphoisoform-mediated signals examines similarities and differences between epithelial and mesenchymal cells in acute and chronic liver injuries and considers Smad linker phosphorylation as a potential target for the chemoprevention of fibro-carcinogenesis

Ecological filtering shapes the impacts of agricultural deforestation on biodiversity

Funding: This project was funded by the National Natural Science Foundation of China (Grants 32122057 and 3198810 to FH) and the Ministry of Science and Technology of China (Grant 2022YFF0802300 to FH), and received further support from Tsinghua University Initiative Scientific Research Program (Grant 20223080017 to LY).The biodiversity impacts of agricultural deforestation vary widely across regions. Previous efforts to explain this variation have focused exclusively on the landscape features and management regimes of agricultural systems, neglecting the potentially critical role of ecological filtering in shaping deforestation tolerance of extant species assemblages at large geographical scales via selection for functional traits. Here we provide a large-scale test of this role using a global database of species abundance ratios between matched agricultural and native forest sites that comprises 71 avian assemblages reported in 44 primary studies, and a companion database of 10 functional traits for all 2,647 species involved. Using meta-analytic, phylogenetic and multivariate methods, we show that beyond agricultural features, filtering by the extent of natural environmental variability and the severity of historical anthropogenic deforestation shapes the varying deforestation impacts across species assemblages. For assemblages under greater environmental variability—proxied by drier and more seasonal climates under a greater disturbance regime—and longer deforestation histories, filtering has attenuated the negative impacts of current deforestation by selecting for functional traits linked to stronger deforestation tolerance. Our study provides a previously largely missing piece of knowledge in understanding and managing the biodiversity consequences of deforestation by agricultural deforestation.Peer reviewe