189 research outputs found
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Sustainable decentralised wastewater treatment schemes in the context of Lobitos, Peru
The implementation of decentralised wastewater treatment systems, such as biodigesters, septic tanks and treatment ponds, provides opportunities for rural or remote communities to be self-reliant and avoid infrastructural connections to faraway urban areas. However, the effectiveness, sustainability and success of such systems is heavily tied to understanding the overall context (geographical, social, cultural, political and economic) in which they are installed, as well as the ease of their operation and maintenance in the long term. Shortcomings to addressing these aspects can lead to the failure of a project. Using the town of Lobitos, located in the Piura District on the northern coast of Peru, as the case study for this research, this paper is discussing and analysing the use of biodigesters as a more sustainable solution over larger municipal wastewater systems in the context of Lobitos. It explains reasons, such as community engagement, behind past failures of such systems and outlines lessons learned from a practitioner’s perspective. It concludes that addressing the local context as well as considering its impact throughout the project cycle, such as installation and future operation and maintenance, helps to ensure continued delivery of safe and sustainable wastewater treatment. </jats:p
SUBORDINATION CONDITIONS FOR A CLASS OF NON-BAZILEVIČ TYPE DEFINED BY USING FRACTIONAL Q-CALCULUS OPERATORS
In this article, we introduce and investigate a new class of non-Bazilevič functions with respect to k-symmetric points defined by using fractional q-calculus operators and q-differentiation. Several interesting subordination results are derived for the functions belonging to this class in the open unit disc. Furthermore, we point out some new and known consequences of our main result
Comparison of in situ and interferometric synthetic aperture radar monitoring to assess bridge thermal expansion
Asset owners responsible for the management and maintenance of bridges value the collection of data that can be processed into useful information to inform decisions about future management of structures. Installing, powering and receiving data from sensors is not always convenient or possible, but satellite monitoring may provide the ability to measure bridge movements and thus provide an indication of potential problems for asset owners to take action on. This study presents the results of satellite monitoring of the Hammersmith flyover, London, UK, using the interferometric synthetic-aperture radar (InSAR) technique. Sentinel-1 (free) and Cosmo-SkyMed (commercial) satellite radar data were processed to provide millimetre-scale measurements of the flyover and surrounding region and validated with in situ sensor measurements. A method was developed for selecting and comparing InSAR measurements with in situ displacement and temperature measurements, making use of bridge geometrical and structural modelling information. The results compare in situ sensor measurements with remote InSAR measurements and show the suitability of such measurements in measuring thermal expansion for some (but not all) bridge assets. The proposed techniques, illustrated with the case study of the Hammersmith flyover, will enable asset owners to collect regular measurements of bridge movements to complement and add value to current inspection methods and potentially give early warning to defective bridge bearings
New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage
© 2016 The Author(s).The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound. In addition, molecular docking revealed that benzo[h]quinolines can correctly dock into the hydrophobic pocket of the targets receptor protein aromatase and CDK2, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. These findings reveal that benzo[h]quinolines act as anti-cancer agents by inducing oxidative stress-mediated DNA damage
Monitoring deformations of Istanbul metro line stations through Sentinel-1 and levelling observations
Turkey, as a developing country, is designing and performing massive construction projects around Istanbul. Beginning from the 1960s, rapid urbanization has been taking place due to industrialization, which brings an increase in the population. Yet, construction projects have been accelerated especially during the last decade, and many new projects are scheduled to be completed in a short time. Ground-based observations are generally carried out to monitor the deformations within construction sites, especially through geometric levelling, and GNSS techniques. However, in most cases, these monitoring measurements are only scheduled within the period of the construction process, and ensuing deformations are usually not considered. In addition to these techniques, the space-based interferometric technique can also be used to define the line of sight surface displacements with high accuracy, using the phase difference between image result for synthetic aperture radar images. In particular, Persistent Scatter Interferometry is one of the interferometric methods that are capable of defining the two-dimensional (vertical and horizontal) deformation for the desired epoch with a high temporal resolution. Thus it can be used as a complementary method for monitoring ground deformations, where the measurement is made by ground-based observations. In this study, the deforming areas related to underground metro construction are investigated through significant displacements between 2015 and 2018 of Sentinel-1 space-borne SAR data using the PSI technique. These results are validated by comparison with available levelling data corresponding to the new metro line
Carbonic anhydrase 9 is a predictive marker of survival benefit from lower dose of bevacizumab in patients with previously treated metastatic colorectal cancer
<p>Abstract</p> <p>Background</p> <p>Carbonic anhydrase 9 (CA9) is a marker for hypoxia and acidosis, which is linked to a poor prognosis in human tumors. The purpose of this comparative analysis was to evaluate whether CA9 and VEGF expression are associated with survival outcomes in patients with metastatic colorectal cancer (mCRC) after treatment with bevacizumab as second or later line treatment.</p> <p>Methods</p> <p>Thirty-one mCRC patients who were treated with bevacizumab-containing chemotherapy as second or later line treatment and who had analyzable tumor paraffin blocks were selected for this study. The planned dose of bevacizumab was 5 mg/kg/2-week. Immunohistochemical (IHC) staining of CA9 and VEGF was performed and their expression was scored by the intensity multiplied by percentage of stained area.</p> <p>Results</p> <p>The overall response rate was 19.4% and the disease control rate (DCR) was 61.3% with 6 partial responses and 13 cases of stable disease. The DCR was significantly higher in patients with a lower CA9 expression score compared to those with a higher score (80.0% vs. 27.3%, respectively, P = 0.004). The patients with a low CA9 expression score also showed better outcomes with regard to the median progression-free survival (P = 0.028) and overall survival (P = 0.026). However, VEGF expression was not associated with the DCR and survival.</p> <p>Conclusion</p> <p>Lower degree of CA9 expression was associated with better clinical outcomes in patients with mCRC treated with lower dose bevacizumab-based chemotherapy. Prospective studies are now needed to determine the correlation between CA9 expression and clinical outcomes after bevacizumab treatment, at different doses and in varied settings.</p
Expression of p89c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells
The c-Myb gene encodes the p75c-Myb isoform and less-abundant proteins generated by alternatively spliced transcripts. Among these, the best known is pc-Mybex9b, which contains 121 additional amino acids between exon 9 and 10, in a domain involved in protein–protein interactions and negative regulation. In hematopoietic cells, expression of pc-Mybex9b accounts for 10–15% of total c-Myb; these levels may be biologically relevant because modest changes in c-Myb expression affects proliferation and survival of leukemic cells and lineage choice and frequency of normal hematopoietic progenitors. In this study, we assessed biochemical activities of pc-Mybex9b and the consequences of perturbing its expression in K562 and primary chronic myeloid leukemia (CML) progenitor cells. Compared with p75c-Myb, pc-Mybex9b is more stable and more effective in transactivating Myb-regulated promoters. Ectopic expression of pc-Mybex9b enhanced proliferation and colony formation and reduced imatinib (IM) sensitivity of K562 cells; conversely, specific downregulation of pc-Mybex9b reduced proliferation and colony formation, enhanced IM sensitivity of K562 cells and markedly suppressed colony formation of CML CD34+ cells, without affecting the levels of p75c-Myb. Together, these studies indicate that expression of the low-abundance pc-Mybex9b isoform has an important role for the overall biological effects of c-Myb in BCR/ABL-transformed cells
Ribosomal S6 Kinase 2 (RSK2) Maintains Genomic Stability by Activating the Atm/p53-Dependent DNA Damage Pathway
10.1371/journal.pone.0074334PLoS ONE89-POLN
The E3 ubiquitin ligase EDD is an adverse prognostic factor for serous epithelial ovarian cancer and modulates cisplatin resistance in vitro
Despite a high initial response rate to first-line platinum/paclitaxel chemotherapy, most women with epithelial ovarian cancer relapse with recurrent disease that becomes refractory to further cytotoxic treatment. We have previously shown that the E3 ubiquitin ligase, EDD, a regulator of DNA damage responses, is amplified and overexpressed in serous ovarian carcinoma. Given that DNA damage pathways are linked to platinum resistance, the aim of this study was to determine if EDD expression was associated with disease recurrence and platinum sensitivity in serous ovarian cancer. High nuclear EDD expression, as determined by immunohistochemistry in a cohort of 151 women with serous ovarian carcinoma, was associated with an approximately two-fold increased risk of disease recurrence and death in patients who initially responded to first-line chemotherapy, independently of disease stage and suboptimal debulking. Although EDD expression was not directly correlated with relative cisplatin sensitivity of ovarian cancer cell lines, sensitivity to cisplatin was partially restored in platinum-resistant A2780-cp70 ovarian cancer cells following siRNA-mediated knockdown of EDD expression. These results identify EDD as a new independent prognostic marker for outcome in serous ovarian cancer, and suggest that pathways involving EDD, including DNA damage responses, may represent new therapeutic targets for chemoresistant ovarian cancer
In vitro hypoxia-conditioned colon cancer cell lines derived from HCT116 and HT29 exhibit altered apoptosis susceptibility and a more angiogenic profile in vivo
Hypoxia is an important selective force in the clonal evolution of tumours. Through HIF-1 and other transcription factors combined with tumour-specific genetic alterations, hypoxia is a dominant factor in the angiogenic phenotype. Cellular adaptation to hypoxia is an important requirement of tumour progression independent of angiogenesis. The adaptive changes, insofar as they alter hypoxia-induced apoptosis, are likely to determine responsiveness to antiangiogenic strategies. To investigate this adaptation of tumour cells to hypoxia, we recreated in vitro the in vivo situation of chronic intermittent exposure to low-oxygen levels. The colon carcinoma cell lines HT29 and HCT116 were subjected to 40 episodes of sublethal hypoxia (4 h) three times a week. The resulting two hypoxia-conditioned cell lines have been maintained in culture for more than 2 years. In both cell lines changes in doubling times occurred: in HT29 an increase, and in HCT116 a decrease. Cell survival in response to hypoxia and to DNA damage differed strikingly in the two cell lines. The HT29 hypoxia-conditioned cells were more resistant than the parental line to a 24 h hypoxic challenge, while those from HCT116 surprisingly were more sensitive. Sensitivity to cisplatin in vitro was also significantly different for the hypoxia-conditioned compared with the parental lines, suggesting a change in pathways leading to apoptosis following DNA damage signaling. The growth of both conditioned cell lines in vivo as xenografts in immunodeficient (SCID) mice was more rapid than their parental lines, and was accompanied in each by evidence of enhanced vascular proliferation as a consequence of the hypoxia-conditioning. Thus the changes in apoptotic susceptibility were independent of altered angiogenesis. The derivation of these lines provides a model for events within hypoxic regions of colon cancers, and for the acquisition of resistance and sensitivity characteristics that may have therapeutic implications for the use of antiangiogenesis drugs
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