138 research outputs found
Synthesis of geopolymer mortar from biomass ashes and forecasting its compressive strength behaviour
The global warming dilemma raised an exigency toward sustainability in the construction industry and compelled scientists to hunt for alternative binders in construction materials. The, geopolymerization as a spectacular technology has arisen as a looming solution to this dilemma. This work assesses the features of geopolymer mortar developed with both industrial and agricultural wastes at ambient temperature curing. The geopolymer mix proportion was evolved in this study using main precursor material as fly ash, ground granulated blast furnace slag (GGBFS), sugarcane bagasse ash (SCBA) or rice husk ash (RHA). Workability and mechanical properties, including compressive strength, flexural strength, and split tensile strength of different mortar mixes with various percentages of RHA and SCBA for 365 days, were evaluated. Geopolymer mortar with 10 % SCBA and 5 % RHA achieved improvements of 25 % and 13.91 % in compressive strength, 10.6 % and 3.5 % in flexural strength, and 35 % and 16.8 % in split tensile strength, respectively. Good geopolymer gel formation is clearly evident from the SEM images of SCBA mortar. The main polymeric bonds Si–O–Al and Si-O-Si are also identified using FTIR. To assess the efficacious use of biomass ashes, resistance to chemical attack using H2SO4, HCl, Na2SiO3, and NaCl solutions for 365 days was studied. It was revealed that SCBA incorporated geopolymer mortar specimens achieved good resistance compared with RHA geopolymer mortar. The relation between the ambient temperature cured geopolymer specimen compressive strength at 28 days and 365 days chemical solution curried geopolymer specimen compressive strength find out using python and obtained R2 values more than 95 %. Also, this research proposed various machine learning techniques such as long short-term memory, support vector regression, random forest regression, XGBOOST, and AdaBOOST algorithms for the prediction of compressive strength of geopolymer using 724 mixture proportions with diverse curing temperatures and varying ages. The XGBOOST algorithm achieved the highest R² value of 0.92, demonstrating its effectiveness for the strength prediction
Consumer Purchasing Decision towards Skin Care Products
The global trend of using skin care products is growing at accelerator rate. As a result of which number of skin care products are emerging as consumer options. The purpose of this study is to analyse the factors influencing consumers decision to purchase skin care products. The study is about the purchasing pattern of people in and around Coimbatore city. A self- designed questionnaire has been designed to collect the information from the respondent. Around 120 samples have been collected for this research. For identifying the purchasing behaviour of the consumer, the respondent was asked to rank the variables based on the Likert scale. The influence of social media on consumer behaviour is also analysed. The statistical analysis that has been done is regression. The insights gained will help the skin care marketers to develop the better growth strategy to sustain the market. This study provides the better understanding of how different variables influence purchasing behaviour
A New Paired Associative Stimulation Protocol with High-Frequency Peripheral Component and High-Intensity 20 Hz Repetitive Transcranial Magnetic Stimulation-A Pilot Study
Paired associative stimulation (PAS) is a stimulation technique combining transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) that can induce plastic changes in the human motor system. A PAS protocol consisting of a high-intensity single TMS pulse given at 100% of stimulator output (SO) and high-frequency 100-Hz PNS train, or "the high-PAS " was designed to promote corticomotoneuronal synapses. Such PAS, applied as a long-term intervention, has demonstrated therapeutic efficacy in spinal cord injury (SCI) patients. Adding a second TMS pulse, however, rendered this protocol inhibitory. The current study sought for more effective PAS parameters. Here, we added a third TMS pulse, i.e., a 20-Hz rTMS (three pulses at 96% SO) combined with high-frequency PNS (six pulses at 100 Hz). We examined the ability of the proposed stimulation paradigm to induce the potentiation of motor-evoked potentials (MEPs) in five human subjects and described the safety and tolerability of the new protocol in these subjects. In this study, rTMS alone was used as a control. In addition, we compared the efficacy of the new protocol in five subjects with two PAS protocols consisting of PNS trains of six pulses at 100 Hz combined with (a) single 100% SO TMS pulses (high-PAS) and (b) a 20-Hz rTMS at a lower intensity (three pulses at 120% RMT). The MEPs were measured immediately after, and 30 and 60 min after the stimulation. Although at 0 and 30 min there was no significant difference in the induced MEP potentiation between the new PAS protocol and the rTMS control, the MEP potentiation remained significantly higher at 60 min after the new PAS than after rTMS alone. At 60 min, the new protocol was also more effective than the two other PAS protocols. The new protocol caused strong involuntary twitches in three subjects and, therefore, its further characterization is needed before introducing it for clinical research. Additionally, its mechanism plausibly differs from PAS with high-frequency PNS that has been used in SCI patients.Peer reviewe
An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS® hydromorphone in patients with chronic cancer pain
<p>Abstract</p> <p>Background</p> <p>Opioid analgesics have proven efficacy in the short-term management of chronic cancer pain, but data on their long-term use is more limited. OROS<sup>® </sup>hydromorphone is a controlled-release formulation of oral hydromorphone that may be particularly well suited to long-term management of chronic cancer pain because it provides stable plasma concentrations and consistent analgesia with convenient once-daily dosing. The objective of this study (DO-118X) was to characterise the pain control achieved with long-term repeated dosing of OROS<sup>® </sup>hydromorphone in patients with chronic cancer pain.</p> <p>Methods</p> <p>In this multicentre, phase III, open-label, single treatment, 1-year extension study, OROS<sup>® </sup>hydromorphone was administered to 68 patients with moderate-to-severe chronic cancer pain, who had successfully completed a short-term equivalence study, and whose pain was controlled with a stable dose of medication (≥ 8 mg OROS<sup>® </sup>hydromorphone or equivalent controlled-release morphine). Patients were started on the dose of OROS<sup>® </sup>hydromorphone equivalent to the opioid dose on which they achieved dose-stable pain control in the equivalence study; dose adjustments were made as necessary and breakthrough pain medication was permitted. Efficacy was assessed with the Brief Pain Inventory (BPI) and patient and investigator global evaluations of treatment effectiveness. No formal statistical analysis was done.</p> <p>Results</p> <p>The mean (standard deviation) duration of exposure to study medication was 139 (129.9) days and the mean (standard deviation) average daily consumption of OROS<sup>® </sup>hydromorphone was 43.7 (28.14) mg/day. All scores were maintained at a mild to moderate severity throughout the study; however, BPI scores for pain at its worst, pain at its least, pain on average, pain right now, and pain relief were slightly worsened at end point compared with baseline. Mean BPI pain interference with daily activities and patient and investigator global evaluation scores also remained generally stable. Treatment effectiveness was rated as fair to good throughout the study. The most frequently reported adverse events were nausea (n = 24, 35.3%), constipation (n = 22, 32.4%), and vomiting (n = 15, 22.1%).</p> <p>Conclusion</p> <p>The results of this extension study suggest that long-term repeated dosing with once-daily OROS<sup>® </sup>hydromorphone can be beneficial in the continuing management of persistent, moderate-to-severe cancer pain.</p
The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.
The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere
Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact.
UNLABELLED: Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes.
SIGNIFICANCE STATEMENT: Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21-Sox2 axis) that can classify ∼50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development
Association between H-RAS T81C genetic polymorphism and gastrointestinal cancer risk: A population based case-control study in China
<p>Abstract</p> <p>Background</p> <p>Gastrointestinal cancer, such as gastric, colon and rectal cancer, is a major medical and economic burden worldwide. However, the exact mechanism of gastrointestinal cancer development still remains unclear. <it>RAS </it>genes have been elucidated as major participants in the development and progression of a series of human tumours and the single nucleotide polymorphism at <it>H-RAS </it>cDNA position 81 was demonstrated to contribute to the risks of bladder, oral and thyroid carcinoma. Therefore, we hypothesized that this polymorphisms in <it>H-RAS </it>could influence susceptibility to gastrointestinal cancer as well, and we conducted this study to test the hypothesis in Chinese population.</p> <p>Methods</p> <p>A population based case-control study, including 296 cases with gastrointestinal cancer and 448 healthy controls selected from a Chinese population was conducted. <it>H-RAS </it>T81C polymorphism was genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay.</p> <p>Results</p> <p>In the healthy controls, the TT, TC and CC genotypes frequencies of <it>H-RAS </it>T81C polymorphism, were 79.24%, 19.87% and 0.89%, respectively, and the C allele frequency was 10.83%. Compared with TT genotype, the TC genotype was significantly associated with an increased risk of gastric cancer (adjusted OR = 3.67, 95%CI = 2.21–6.08), while the CC genotype showed an increased risk as well (adjusted OR = 3.29, 95%CI = 0.54–19.86), but it was not statistically significant. In contrast, the frequency of TC genotype was not significantly increased in colon cancer and rectal cancer patients. Further analysis was performed by combining TC and CC genotypes compared against TT genotype. As a result, a statistically significant risk with adjusted OR of 3.65 (95%CI, 2.22–6.00) was found in gastric cancer, while no significant association of <it>H-RAS </it>T81C polymorphism with colon cancer and rectal cancer was observed.</p> <p>Conclusion</p> <p>These findings indicate, for the first time, that there is an <it>H-RAS </it>T81C polymorphism existing in Chinese population, and this SNP might be a low penetrance gene predisposition factor for gastric cancer.</p
Retinoblastoma Loss Modulates DNA Damage Response Favoring Tumor Progression
Senescence is one of the main barriers against tumor progression. Oncogenic signals in primary cells result in oncogene-induced senescence (OIS), crucial for protection against cancer development. It has been described in premalignant lesions that OIS requires DNA damage response (DDR) activation, safeguard of the integrity of the genome. Here we demonstrate how the cellular mechanisms involved in oncogenic transformation in a model of glioma uncouple OIS and DDR. We use this tumor type as a paradigm of oncogenic transformation. In human gliomas most of the genetic alterations that have been previously identified result in abnormal activation of cell growth signaling pathways and deregulation of cell cycle, features recapitulated in our model by oncogenic Ras expression and retinoblastoma (Rb) inactivation respectively. In this scenario, the absence of pRb confers a proliferative advantage and activates DDR to a greater extent in a DNA lesion-independent fashion than cells that express only HRasV12. Moreover, Rb loss inactivates the stress kinase DDR-associated p38MAPK by specific Wip1-dependent dephosphorylation. Thus, Rb loss acts as a switch mediating the transition between premalignant lesions and cancer through DDR modulation. These findings may have important implications for the understanding the biology of gliomas and anticipate a new target, Wip1 phosphatase, for novel therapeutic strategies
- …