Explore the vast range of titles available.

A band anticrossing (BAC) k.p model was applied to calculate the valence band structure of wurtzite GaN 1−x Sb x dilute alloys. BAC parameters such as localized Sb-impurity energy level and coupling parameter were determined by using experimental results. The restructuring of the valence band is found as a result of the interaction of the Sb-related impurity state with the extended states of the valence band of the host GaN. The dependencies of the energy band gap and effective masses of different energy sub-bands of GaN 1−x Sb x on Sb content are investigated. Results predict a large band gap reduction with the incorporation of dilute amounts of Sb, which is a key parameter for device design. Analysis of carrier effective masses show that changes in Sb content and their effects can affect the transport properties of GaNSb alloys.

The floodplain wetland habitat in the lower Gangetic plains of West Bengal played a significant role in protecting from environmental degradation like pollution, lowering groundwater table, natural hazards, and others as well as supports for human wellbeing. Thus, it is needed to investigate the health status of wetlands and suggest restoration strategies to protect the livelihood patterns dependent on wetlands. This paper presents the health of the wetland ecosystem by comprising the wetland ecosystem health index (WHI) in 2011 and 2018 at the block level of Malda district, as a part of the lower Gangetic flood plain using the pressure–state–response model (PSR model) and AHP method. A total number of six Landsat satellite images and statistical census data were used to determine the wetland health. Wetlands are classified as very healthy (2.81–3.33), healthy (2.41–2.80), sub-healthy (2.01–2.40), unhealthy (1.61–2.00), and sick (0–1.60) category on the basis of the wetland ecosystem health index score. The results of this study showed that the wetlands located surrounding English Bazar, Manikchak, Ratua-II, and Kaliachak-II blocks have a sub-healthy to very healthy condition in 2011 but changed to unhealthy to sick category in 2018 due to the increase of rapid urbanization, population density, and development activities. These areas have belonged to the sub-healthy to sick category in the year 2011 as well as 2018 due to high wetland pressure. Our observation reveals that the ecosystem service value provided by wetlands decreased by 62.51% and 20.46 in the observed period. Management of WEH should emphasize on large (>100 ha) and medium (51–100 ha) sizes of wetlands in the Diara region of West Bengal. Developing local-level institutions and setting restoration goals are useful strategies to manage wetland resources, and protecting biodiversity should be guided by the Government organization and NGOs.

Artemisinin is the frontline fast-acting anti-malarial against P. falciparum . Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum -infected patients received standard ASSP therapy during August 2015–January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC 1/2 ), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene ( pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps ). Of 180 P. falciparum positive patients, 9.5% showed increased PC 1/2 (> 5.5 h), among them eleven isolates (6.1%) showed reduced sensitivity to RSA. In 4.4% of cases, parasites were not cleared by 72 h and showed prolonged PC 1/2 (5.6 h) (P < 0.005) along with significantly higher RSA (2.2%) than cured patients (0.4%). None of day-3 positive isolates contained the pfkelch13 mutation implicated in artemisinin resistance. Parasite recrudescence was observed in 5.6% patients, which was associated with triple dhfr – dhps (A 16 I 51 R 59 N 108 I 164 –S 436 G 437 K 540 G 581 T 613 ) combination mutation. Emergence of reduced sensitivity to artesunate-sulfadoxine-pyrimethamine, in central India highlighted the risk toward spread of resistant parasite across different parts of India. Day-3 positive parasite, featuring the phenotype of artemisinin-resistance without pfkelch13 mutation, suggested kelch13 -independent artemisinin-resistance.

MAP4K4 is a Ste20 member and reported to play important roles in various pathologies, including in cancer. However, the mechanism by which MAP4K4 promotes pancreatic cancer is not fully understood. It is suggested that MAP4K4 might function as a cancer promoter via specific downstream target(s) in an organ-specific manner. Here we identified MLK3 as a direct downstream target of MAP4K4. The MAP4K4 and MLK3 associates with each other, and MAP4K4 phosphorylates MLK3 on Thr738 and increases MLK3 kinase activity and downstream signaling. The phosphorylation of MLK3 by MAP4K4 promotes pancreatic cancer cell proliferation, migration, and colony formation. Moreover, MAP4K4 is overexpressed in human pancreatic tumors and directly correlates with the disease progression. The MAP4K4-specific pharmacological inhibitor, GNE-495, impedes pancreatic cancer cell growth, migration, induces cell death, and arrests cell cycle progression. Additionally, the GNE-495 reduced the tumor burden and extended survival of the KPC mice with pancreatic cancer. The MAP4K4 inhibitor also reduced MAP4K4 protein expression, tumor stroma, and induced cell death in murine pancreatic tumors. These findings collectively suggest that MLK3 phosphorylation by MAP4K4 promotes pancreatic cancer, and therefore therapies targeting MAP4K4 might alleviate the pancreatic cancer tumor burden in patients.

The incidence and mortality of hepatocellular carcinoma (HCC) are on a rise in the Western countries including US, attributed mostly to late detection. Sorafenib has been the first-line FDA-approved drug for advanced unresectable HCC for almost a decade, but with limited efficacy due to the development of resistance. More recently, several other multi-kinase inhibitors (lenvatinib, cabozantinib, regorafenib), human monoclonal antibody (ramucirumab), and immune checkpoint inhibitors (nivolumab, pembrolizumab) have been approved as systemic therapies. Despite this, the median survival of patients is not significantly increased. Understanding of the molecular mechanism(s) that govern HCC resistance is critically needed to increase efficacy of current drugs and to develop more efficacious ones in the future. Our studies with sorafenib-resistant (soraR) HCC cells using transcription factor RT 2 Profiler PCR Arrays revealed an increase in E26 transformation–specific-1 (Ets-1) transcription factor in all soraR cells. HCC TMA studies showed an increase in Ets-1 expression in advanced HCC compared to the normal livers. Overexpression or knocking down Ets-1 modulated sorafenib resistance-related epithelial–mesenchymal transition (EMT), migration, and cell survival. In addition, the soraR cells showed a significant reduction of mitochondrial damage and mitochondrial reactive oxygen species (mROS) generation, which were antagonized by knocking down Ets-1 expression. More in-depth analysis identified GPX-2 as a downstream mediator of Ets-1-induced sorafenib resistance, which was down-regulated by Ets-1 knockdown while other antioxidant pathway genes were not affected. Interestingly, knocking down GPX2 expression significantly increased sorafenib sensitivity in the soraR cells. Our studies indicate the activation of a novel Ets-1–GPX2 signaling axis in soraR cells, targeting which might successfully antagonize resistance and increase efficacy.

Our previous studies indicated that combination of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and PPARγ ligand Troglitazone (TZD), can induce significant apoptosis in various TRAIL-resistant prostate and hepatocellular carcinoma (HCC) cells. These also suggested serine/threonine kinase AMP-activated protein kinase (AMPK) to be a mediator of TRAIL-TZD-induced apoptosis. To further validate AMPK’s role in TRAIL sensitization, we determined the apoptotic potential of TRAIL in combination with the natural compound Berberine (BBR), the latter being a potent activator of AMPK. These demonstrated a significant reduction of cell viability and induction of apoptosis (increased cleavage of caspase 3, 8, 9) when treated with TRAIL-BBR combination. This apoptosis is attenuated in cells overexpressing AMPKα-dominant negative (DN) or following AMPKα knockdown, confirming involvement of AMPK. To identify potential downstream mediators involved, an apoptosis RT 2 PCR array analysis was performed. These showed induction of several genes including TNFRSF10B (expresses DR5) and Harakiri following BBR treatment, which were further validated by qPCR analysis. Furthermore, knocking down DR5 expression significantly attenuated TRAIL-BBR-induced apoptosis, suggesting DR5 to be a mediator of this apoptosis. Our studies indicate that combination of TRAIL and AMPK activator BBR might be an effective means of ameliorating TRAIL-resistance involving DR5 in advanced cancer.

GaAsSb epitaxial layers are grown using liquid-phase epitaxy (LPE) technique over < 100 > oriented GaAs substrates. The layers contain up to 1.84% Sb, as estimated from high-resolution X-ray diffraction (HRXRD) measurements. Detailed photoluminescence (PL) studies are made on the as-grown and high-temperature-annealed layers to reveal various electronic transitions in the materials. Excitation power-dependent PL measurements are done to investigate the origin of each of the transitions. The bandgap energy, obtained from PL, shows a reduction of approximately 17 meV per at% increase in Sb content, which agrees well with the bandgap reduction, calculated with the band anticrossing (BAC) model. Analysis of the temperature-dependent PL data, using Bose–Einstein model, indicates that both the electron–phonon interaction and the average phonon temperatures strongly depend on the Sb content in GaAsSb.

Mixed lineage kinase 3 (MLK3), a MAP3K member has been envisioned as a viable drug target in cancer, yet its detailed function and signaling is not fully elucidated. We identified that MLK3 tightly associates with an oncogene, PAK1. Mammalian PAK1 being a Ste20 (MAP4K) member, we tested whether it is an upstream regulator of MLK3. In contrast to our hypothesis, MLK3 activated PAK1 kinase activity directly, as well as in the cells. Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3. Stable overexpression of PAK1S204A in breast cancer cells, impedes migration, invasion, and NFĸB activity. In vivo breast cancer cell tumorigenesis is significantly reduced in tumors expressing PAK1S204A mutant. These results suggest that mammalian PAK1 does not act as a MAP4K and MLK3-induced direct activation of PAK1 plays a key role in breast cancer tumorigenesis.

Background Chronic obstructive pulmonary disease (COPD) is a condition in which airflow limitation becomes irreversible over time, often resulting from long-term exposure to environmental pollutants, harmful particles, smoke, and biomass fuel. Beyond FEV1, identifying a more specific biomarker to predict COPD progression remains a challenge. Soluble urokinase-type plasminogen activator receptor (suPAR) expression increases in the respiratory epithelial cells of COPD patients. This study aimed to evaluate serum suPAR levels across different grades of stable COPD patients. Methods Two hundred stable COPD patients (148 males and 52 females) were recruited after obtaining informed consent. Blood samples were collected, and serum suPAR levels were measured in all participants. Results Serum suPAR levels were elevated in COPD patients at Global Initiative for Obstructive Lung Disease (GOLD) stages IV and III (6.38 ± 0.05 ng/ml and 5.82 ± 0.18 ng/ml, respectively) compared to those at GOLD stages II and I (5.15 ± 0.25 ng/ml and 4.17 ± 0.29 ng/ml). A one-way ANOVA confirmed that the differences between groups were statistically significant (F = 428.83, p < 0.001). Conclusions This study suggests that serum suPAR levels can serve as a diagnostic marker for COPD. As low-grade pulmonary inflammation increases with disease severity, suPAR levels also rise. Additionally, this marker may be useful for monitoring the prognosis of stable COPD and assessing treatment response.

Mixed Lineage Kinase 3 (MLK3) is a viable target for neoplastic diseases; however, it is unclear whether its activators or inhibitors can act as anti-neoplastic agents. We reported that the MLK3 kinase activity was higher in triple-negative (TNBC) than in hormone receptor-positive human breast tumors, where estrogen inhibited MLK3 kinase activity and provided a survival advantage to ER + breast cancer cells. Herein, we show that in TNBC, the higher MLK3 kinase activity paradoxically promotes cancer cell survival. Knockdown of MLK3 or MLK3 inhibitors, CEP-1347 and URMC-099, attenuated tumorigenesis of TNBC cell line and Patient-Derived (PDX) xenografts. The MLK3 kinase inhibitors decreased both the expression and activation of MLK3, PAK1, and NF-kB protein and caused cell death in TNBC breast xenografts. RNA-seq analysis identified several genes downregulated by MLK3 inhibition, and the NGF/TrkA MAPK pathway was significantly enriched in tumors sensitive to growth inhibition by MLK3 inhibitors. The TNBC cell line unresponsive to kinase inhibitor had substantially lower TrkA, and overexpression of TrkA restored the sensitivity to MLK3 inhibition. These results suggest that the functions of MLK3 in breast cancer cells depend on downstream targets in TNBC tumors expressing TrkA, and MLK3 kinase inhibition may provide a novel targeted therapy.