Levelling of heating and vehicle demand in distribution networks using randomised device control

Rising demand from electrical heating and vehicles will drive major distribution network reinforcement costs unless 24-hour demand profiles can be levelled. We propose a demand response scheme in which the electricity supplier provides a signal to a “smart home” control unit that manages the consumer’s appliances using a novel approach for reconciliation of the consumer’s needs and desires with the incentives supplied by the signal. The control unit allocates demand randomly in timeslots that are acceptable to the consumer but with a probability biased in accordance with the signal provided by the supplier. This behaviour ensures that demand response is predictable and stable and allows demand to be shaped in a way that can satisfy distribution network constraints

The relation characteristics of personality of managers working in Iran University of Medical Sciences with success and desirable job

Background: Several studies suggest the existence of an effective relationship between individuals' characteristics and important factors such as occupational and organizational performance, job satisfaction, organizational commitment, and etc. This study was designed based on the dimensions of personality (introversion/extroversion) of managers of Iran University of Medical Sciences at three levels (executive, middle and senior) with their career success rate. Methods: This was a cross-sectional descriptive study, whose population was all managers of Iran University of Medical Sciences. To collect data, two valid and reliable questionnaires were used. The first questionnaire assessed personality characteristics of each director, and the second measured occupational success. Related tests such as Pearson correlation test and independent comparison (independent t-test) at a significance level of 0.05 were used for data analysis. Results: Findings revealed no significant relationship between variables of introversion and extroversion and occupational success among the senior managers, (p > 0.05). However, there was a direct but incomplete relationship between introversion and extroversion, which correlated with job success among middle and executives managers. Conclusion: It seems that in all three levels of managers, if the managers communicated more with employees and if the subject of communication was more of executive nature, the correlation rate would increase between extroversion and introversion with job success variables. Therefore, it is suggested to give attention to organizational interaction and communication, and contingency variables such as organization condition, structure, formality and complexity

Accommodating renewable generation through an aggregator-focused method for inducing demand side response from electricity consumers

Consortium project with Cranfield University The file attached is a postprint of a paper submitted to and accepted for publication in [journal] and is subject to Institution of Engineering and Technology Copyright. The copy of record is available at IET Digital Library"The ability to influence electricity demand from domestic and small business consumers so that it can be matched to intermittent renewable generation and distribution network constraints is a key capability of a smart grid. This involves signalling to consumers to indicate when electricity use is desirable or undesirable. However simply signalling a time dependent price does not always achieve the required demand response and can result in unstable system behaviour. We propose a demand response scheme in which an aggregator mediates between the consumer and the market and provides a signal to a “smart home” control unit that manages the consumer’s appliances using a novel method for reconciliation of the consumer’s needs and preferences with the incentives supplied by the signal. This method involves random allocation of demand within timeslots acceptable to the consumer with a bias depending on the signal provided. By simulating a population of domestic consumers using heat pumps and electric vehicles with properties consistent with UK national statistics, we show the method allows total demand to be predicted and shaped in a way that can simultaneously match renewable generation and satisfy network constraints, leading to benefits from reduced use of peaking plant and avoided network reinforcement.Engineering and Physical Sciences Research Council (EPSRC) under the CASCADE project (EP/GO59969/1)

The nuclear lamina couples mechanical forces to cell fate in the preimplantation embryo via actin organization

During preimplantation development, contractile forces generated at the apical cortex segregate cells into inner and outer positions of the embryo, establishing the inner cell mass (ICM) and trophectoderm. To which extent these forces influence ICM-trophectoderm fate remains unresolved. Here, we found that the nuclear lamina is coupled to the cortex via an F-actin meshwork in mouse and human embryos. Actomyosin contractility increases during development, upregulating Lamin-A levels, but upon internalization cells lose their apical cortex and downregulate Lamin-A. Low Lamin-A shifts the localization of actin nucleators from nucleus to cytoplasm increasing cytoplasmic F-actin abundance. This results in stabilization of Amot, Yap phosphorylation and acquisition of ICM over trophectoderm fate. By contrast, in outer cells, Lamin-A levels increase with contractility. This prevents Yap phosphorylation enabling Cdx2 to specify the trophectoderm. Thus, forces transmitted to the nuclear lamina control actin organization to differentially regulate the factors specifying lineage identity

The prognostic impact of WT1 expression levels, mutations, and SNP rs16754 in AML patients: A retrospective cohort study

Background & Objective: The clinical outcomes and treatment options for acute myeloid leukemia (AML) patients are highly dependent upon molecular markers. In this study, Wilms tumor 1 (WT1) (exons 7 and 9) mutations, single-nucleotide polymorphism (SNP) rs16754, and WT1 expression levels in 130 random AML patients were screened; FMs-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD), nucleophosmin (NPM1), and CCAAT/enhancer-binding protein alpha (CEBPA) mutations were also evaluated. Materials & Methods: Overall, 130 AML patients were recruited for this study. WT1 mutations were determined by Sanger sequencing, and expression levels were determined by real-time polymerase chain reaction (PCR). The Kaplan-Meier method was used to calculate overall survival (OS) and disease-free survival (DFS). Results: The frequency of WT1 mutations in the study population was 5.4, and it did not affect OS (P=0.98), DFS (P=0.97), or complete remission (CR) rates in AML patients. The major allele of SNP rs16754 in the current study was A. No significant differences were found for OS (P=0.52), DFS (P=0.42), or CR rates among all SNP rs16754 genotypes. The overexpression of WT1 was observed in 83 of patients at diagnosis. No significant difference was found for OS (P=0.84), DFS (P=0.82), or CR rates between AML patients with high and low WT1 expression levels. Conclusion: The results of the current study do not support WT1 mutation, SNP rs16754, or WT1 overexpression at diagnosis, as they were found to be poor prognostic markers in AML patients. © 2021, Zanjan University of Medical Sciences and Health Services. All rights reserved

FLT3-ITD compared with DNMT3A R882 mutation is a more powerful independent inferior prognostic factor in adult acute myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation: A retrospective cohort study Allojenik hematopoetik kök hücre nakli sonrası yeti�kin akut myeloid lösemi hastalarında, FLT3-ITD, DNMT3A R882 mutasyonu ile kar�ıla�tırıldı�ında daha güçlü bir ba�ımsız kötü prognostik faktördür: Retrospektif kohort çalı�ması

Objective: This study aimed to evaluate DNMT3A exon 23 mutations and their prognostic impacts in the presence of NPM1 and FLT3 mutations in acute myeloid leukemia (AML) patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). Materials and Methods: This study comprised 128 adult AML patients referred to the Hematology-Oncology and Stem Cell Research Center of Shariati Hospital. NPM1 and FLT3-ITD mutations were detected by fragment analysis. For DNMT3A exon 23 mutation analysis, we used Sanger sequencing. Overall survival (OS) and relapse-free survival (RFS) curves were estimated by the Kaplan-Meier method and the log-rank test was used to calculate differences between groups. Results: The prevalence of DNMT3A exon 23 mutations was 15.6 and hotspot region R882 mutations were prominent. RFS and OS were compared in patients with and without DNMT3A exon 23 mutations using univariate analysis and there was no significant difference between these groups of patients. On the contrary, the FLT3-ITD mutation significantly reduced the OS (p=0.009) and RFS (p=0.006) in AML patients after allogeneic HSCT. In the next step, patients with AML were divided into four groups regarding FLT3-ITD and DNMT3A mutations. Patients with DNMT3A R882mut/FLT3-ITDpos had the worst OS and RFS. These results indicate that DNMT3A mutations alone do not affect the clinical outcomes of AML patients undergoing allogeneic HSCT, but when accompanied by FLT3-ITD mutations, the OS was significantly reduced (5-year OS 0 for DNMT3A R882mut/ FLT3-ITDpos patients vs. 62 DNMT3A R882wt/FLT3-ITDneg, p=0.025) and the relapse rate increased. Conclusion: It can be deduced that DNMT3A R882mut/FLT3-ITDpos is an unfavorable prognostic factor in AML patients even after allogeneic HSCT. © 2018 by Turkish Society of Hematology

Breast cancer cells imaging by targeting methionine transporters with gadolinium-based nanoprobe

Purpose: Early cancer diagnosis using MRI imaging is of high global interest as a non-invasive and powerful modality. In this study, methionine was conjugated on gadolinium-based mesoporous silica nanospheres to evaluate intra-cellular uptake and its accumulation in human breast cancer cells. Procedures: The contrast agent was synthesized and characterized using different techniques including N2 physisorption, thermal gravimetric analysis, dynamic light scattering, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The intra-cellular uptake of Gd3+ was measured by ICP-AES, fluorescent microscopy, and flow cytometry. Finally, cellular and tumor MR imaging were performed to determine in vitro and in vivo relaxometry. Results: According to the results, the contrast agents accumulated in tumor cells both in vitro and in vivo. There was no significant cellular toxicity on either normal or cancer cells along with strong intense signal on T1 compared to the unlabeled cells. Conclusions: The results showed that the novel contrast agent could become a useful tool in early detection of cancer. © 2014 World Molecular Imaging Society

Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Many cancer cells produce interleukin-6 (IL-6), a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of <it>IL-6 </it>modulators, i.e. IL-1β, prostaglandin E₂, 17β-estradiol, and 1,25-dihydroxyvitamin D₃, on expression and synthesis of the cytokine at different stages of tumour progression.</p> <p>Methods</p> <p>We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the <it>IL-6 </it>gene promoter.</p> <p>Results</p> <p><it>IL-6 </it>mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml) to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10^-7M) reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the <it>IL-6 </it>promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the <it>IL-6 </it>gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-<it>myc </it>proto-oncogene expression. These effects were inhibited by 10^-8M 1,25-dihydroxyvitamin D₃.</p> <p>Conclusion</p> <p>In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally affected, if at all, by PGE₂, 1,25-dihydroxyvitamin D₃, and 17β-estradiol. However, IL-6 is highly abundant in undifferentiated tumour cells and is effectively stimulated by IL-1β. In case of overexpression of an <it>IL-6 </it>gene variant with extreme sensitivity to IL-1β, massive release of the cytokine from undifferentiated tumour cells may accelerate progression towards malignancy by paracrine action on more differentiated tumour cells with a still functioning proliferative IL-6 signalling pathway.</p

Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis

Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress. Additionally, mahanine-treated Leishmania-infected macrophages exhibited anti-amastigote activity by nitric oxide (NO)/ROS generation along with suppression of uncoupling protein 2 and Th1-biased cytokines response through modulating STAT pathway. Moreover, we have demonstrated the interaction of a few antioxidant enzymes present in parasite with mahanine through molecular modeling. Reduced genetic and protein level expression of one such enzyme namely ascorbate peroxidase was also observed in mahanine-treated promastigotes. Furthermore, oral administration of mahanine in acute murine model exhibited almost complete reduction of parasite burden, upregulation of NO/iNOS/ROS/IL-12 and T cell proliferation. Taken together, we have established a new function of mahanine as a potent antileishmanial molecule, capable of inducing ROS and exploit antioxidant enzymes in parasite along with modulation of host’s immune response which could be developed as an inexpensive and nontoxic therapeutics either alone or in combination