Preliminary evaluation of decay heat in a HCPB DEMO fusion reactor

In previous studies, energy generation in a fusion DEMO reactor was estimated by accounting for prompt heat production only, neglecting the decay heat generated from the decay of radioactive isotopes. In this work, based on a helium-cooled pebble bed (HCPB) ceramic blanket which is one of the European DEMO concepts, the decay heat generated in different components is estimated as a function of cooling time is performed in order to assess its contribution. The code system HERCULES, by coupling the MCNP particle transport and the activation inventory FISPACT, is used for the calculation of prompt energy deposition and decay heat for all components in the HCPB DEMO reactor. It is found that, relative to fusion power of 2.7GW, the activated nuclides generated decay heat are <3% at the cooling time of 1 second assuming a power plant operation scenarios. This study suggests that the material selection has a significant impact on decay heat

Convolutional neural networks for challenges in automated nuclide identification

Improvements in Radio-Isotope IDentification (RIID) algorithms have seen a resurgence in interest with the increased accessibility of machine learning models. Convolutional Neural Network (CNN)-based models have been developed to identify arbitrary mixtures of unstable nuclides from gamma spectra. In service of this, methods for the simulation and pre-processing of training data were also developed. The implementation of 1D multi-class, multi-label CNNs demonstrated good generalisation to real spectra with poor statistics and significant gain shifts. It is also shown that even basic CNN architectures prove reliable for RIID under the challenging conditions of heavy shielding and close source geometries, and may be extended to generalised solutions for pragmatic RIID

Rokhlin Dimension for Flows

This research was supported by GIF Grant 1137/2011, SFB 878 Groups, Geometry and Actions and ERC Grant No. 267079. Part of the research was conducted at the Fields institute during the 2014 thematic program on abstract harmonic analysis, Banach and operator algebras, and at the Mittag–Leffler institute during the 2016 program on Classification of Operator Algebras: Complexity, Rigidity, and Dynamics.Peer reviewedPostprin

Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by lipoic acid: role in cancer prevention and therapy

<p>Abstract</p> <p>Background</p> <p>Lipoic acid (LA), a potent antioxidant, has been used as a dietary supplement to prevent and treat many diseases, including stroke, diabetes, neurodegenerative and hepatic disorders. Recently, potent anti-tumorigenic effects induced by LA were also reported and evident as assayed by suppression of cell proliferation and induction of apoptosis in malignant cells. However, the mechanism by which LA elicits its chemopreventive effects remains unclear.</p> <p>Methods and Results</p> <p>Herein, we investigated whether LA elicits its anti-tumor effects by inducing cell cycle arrest and cell death in human promyelocytic HL-60 cells. The results showed that LA inhibits both cell growth and viability in a time- and dose-dependent manner. Disruption of the G₁/S and G₂/M phases of cell cycle progression accompanied by the induction of apoptosis was also observed following LA treatment. Cell cycle arrest by LA was correlated with dose-dependent down regulation of Rb phosphorylation, likely via suppression of E2F-dependent cell cycle progression with an accompanying inhibition of cyclin E/cdk2 and cyclin B1/cdk1 levels. Evidence supporting the induction of apoptosis by LA was based on the appearance of sub-G₁peak in flow cytometry analysis and the cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product in immunoblot assays. Apoptosis elicited by LA was preceded by diminution in the expression of anti-apoptotic protein bcl-2 and increased expression of apoptogenic protein bax, and also the release and translocation of apoptosis inducing factor AIF and cytochrome c from the mitochondria to the nucleus, without altering the subcellular distribution of the caspases.</p> <p>Conclusion</p> <p>This study provides evidence that LA induces multiple cell cycle checkpoint arrest and caspase-independent cell death in HL-60 cells, in support of its efficacious potential as a chemopreventive agent.</p

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

A Combination of Nutriments Improves Mitochondrial Biogenesis and Function in Skeletal Muscle of Type 2 Diabetic Goto–Kakizaki Rats

BACKGROUND: Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA), and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-alpha (Ppar alpha), peroxisome proliferator-activated receptor-delta (Ppar delta), and carnitine palmitoyl transferase-1 (Mcpt-1) and activity of mitochondrial complex I and II in skeletal muscle. All of these effects of mitochondrial nutrients are comparable to that of the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain. CONCLUSIONS/SIGNIFICANCE: These data suggest that a combination of mitochondrial targeting nutrients may improve skeletal mitochondrial dysfunction and exert hypoglycemic effects, without causing weight gain

An Improved Protocol for N-Glycosylation Analysis of Gel-Separated Sialylated Glycoproteins by MALDI-TOF/TOF

Different glycoforms of some proteins have been identified as differential spots for certain diseases in 2-DE, indicating disease-related glycosylation changes. It is routine to determine the site-specific glycosylation of nonsialylated N-glycoproteins from a single gel spot, but some obstacles still exist in analyzing sialylated glycoproteins due to the lability and higher detection limit of acid glycans in MALDI-TOF/TOF analysis. Thus, we present an improved protocol here. Tryptic glycopeptides were separated and subjected to MALDI-TOF/TOF analysis, resulting in the identification of site-specific glycosylation of high-intensity glycopeptides. Sequential deglycosylation and desialylation were used to improve the identification of glycosylation sites and desialylated glycans. The site-specific glycosylation of large glycopeptides and low-intensity glycopeptides was deduced based on the masses of glycopeptides, deglycosylated peptides and desialylated glycans. By applying it to 2-DE separated human serum, the difference of N-glycosylation was successfully determined for α1-antitrypsin between different gel spots