Optimization of flux-surface density variation in stellarator plasmas with respect to the transport of collisional impurities

Avoiding impurity accumulation is a requirement for steady-state stellarator operation. The accumulation of impurities can be heavily affected by variations in their density on the flux-surface. Using recently derived semi-analytic expressions for the transport of a collisional impurity species with high-$Z$ and flux-surface density-variation in the presence of a low-collisionality bulk ion species, we numerically optimize the impurity density-variation on the flux-surface to minimize the radial peaking factor of the impurities. These optimized density-variations can reduce the core impurity density by $0.75^Z$ (with $Z$ the impurity charge number) in the Large Helical Device case considered here, and by $0.89^Z$ in a Wendelstein 7-X standard configuration case. On the other hand, when the same procedure is used to find density-variations that maximize the peaking factor, it is notably increased compared to the case with no density-variation. This highlights the potential importance of measuring and controlling these variations in experiments.Comment: 19 figures, 17 pages. Accepted into Nuclear Fusio

Rapid and asymmetric divergence of duplicate genes in the human gene coexpression network

BACKGROUND: While gene duplication is known to be one of the most common mechanisms of genome evolution, the fates of genes after duplication are still being debated. In particular, it is presently unknown whether most duplicate genes preserve (or subdivide) the functions of the parental gene or acquire new functions. One aspect of gene function, that is the expression profile in gene coexpression network, has been largely unexplored for duplicate genes. RESULTS: Here we build a human gene coexpression network using human tissue-specific microarray data and investigate the divergence of duplicate genes in it. The topology of this network is scale-free. Interestingly, our analysis indicates that duplicate genes rapidly lose shared coexpressed partners: after approximately 50 million years since duplication, the two duplicate genes in a pair have only slightly higher number of shared partners as compared with two random singletons. We also show that duplicate gene pairs quickly acquire new coexpressed partners: the average number of partners for a duplicate gene pair is significantly greater than that for a singleton (the latter number can be used as a proxy of the number of partners for a parental singleton gene before duplication). The divergence in gene expression between two duplicates in a pair occurs asymmetrically: one gene usually has more partners than the other one. The network is resilient to both random and degree-based in silico removal of either singletons or duplicate genes. In contrast, the network is especially vulnerable to the removal of highly connected genes when duplicate genes and singletons are considered together. CONCLUSION: Duplicate genes rapidly diverge in their expression profiles in the network and play similar role in maintaining the network robustness as compared with singletons. Contact: [email protected] Supplementary information: Please see additional files

Genomic Imprinting Mediates Social Interactions Within Honeybee (Apis mellifera) Colonies.

Patient centeredness means providing care that is respectful of and responsive to individual patient preferences, needs and values, and ensuring that patient values guide all clinical decisions’.The concept assumes that both physicians and patients are experts; physicians in diagnostic and therapeutic procedures, patients by their personal experience. Van der Eijk examined how patient-centeredness could be defined, measured and improved in Parkinson care. Patients with Parkinson's disease(PD) become progressively disabled due to a mixture of cognitive, emotional and motor symptoms. Given the complex nature of the disease, delivering patient-centered care to PD patients is challenging. Preferably, Parkinson care is provided by a collaborative team of physicians, nurses, psychosocial caregivers and allied health experts. 'Patient-centeredness' implies that patients are invited to participate within this team. PD patients currently assume a passive role in healthcare, partially because this is the traditional approach, but also because they lack the tools to self-manage their condition. Van der Eijk found out that PD patients experience a lack of collaboration between their healthcare professionals. Additionally, patients urgently call for more and personally tailored information as well as emotional support to cope better with their disease. Van der Eijk collected patient-experiences in the Netherlands, Canada and the United States and evaluated regional multidisciplinary healthcare networks and online health communities. These innovations may improve the patient-centeredness of care and enhance communication among health professionals and patients, and support coordination of care across institutions. A personal health community is a private community governed by individual patients. Apart from the patient, participants include the caregiver and one or more (ideally all) health professionals involved. Patients favor the possibility to interact with their health professionals for emotional support and to obtain medical information. When technically well facilitated, the concept stimulates active patient involvement in their own health and healthcare

Redox-regulating sirtuins in aging, caloric restriction, and exercise.

The consequence of decreased nicotinamide adenine dinucleotide (NAD(+)) levels as a result of oxidative challenge is altered activity of sirtuins, which, in turn, brings about a wide range of modifications in mammalian cellular metabolism. Sirtuins, especially SIRT1, deacetylate important transcription factors such as p53, forkhead homeobox type O proteins, nuclear factor κB, or peroxisome proliferator-activated receptor γ coactivator 1α (which controls the transcription of pro- and antioxidant enzymes, by which the cellular redox state is affected). The role of SIRT1 in DNA repair is enigmatic, because it activates Ku70 to cope with double-strand breaks, but deacetylation of apurinic/apyrimidinic endonuclease 1 and probably of 8-oxoguanine-DNA glycosylase 1 decreases the activity of these DNA repair enzymes. The protein-stabilizing effects of the NAD+-dependent lysine deacetylases are readily related to housekeeping and redox regulation. The role of sirtuins in caloric restriction (CR)-related longevity in yeast is currently under debate. However, in mammals, it seems certain that sirtuins are involved in many cellular processes that mediate longevity and disease prevention via the effects of CR through the vascular, neuronal, and muscular systems. Regular physical exercise-mediated health promotion also involves sirtuin-regulated pathways including the antioxidant-, macromolecular damage repair-, energy-, mitochondrial function-, and neuronal plasticity-associated pathways. This review critically evaluates these findings and points out the age-associated role of sirtuins

N17 Modifies mutant Huntingtin nuclear pathogenesis and severity of disease in HD BAC transgenic mice.

The nucleus is a critical subcellular compartment for the pathogenesis of polyglutamine disorders, including Huntington's disease (HD). Recent studies suggest the first 17-amino-acid domain (N17) of mutant huntingtin (mHTT) mediates its nuclear exclusion in cultured cells. Here, we test whether N17 could be a molecular determinant of nuclear mHTT pathogenesis in vivo. BAC transgenic mice expressing mHTT lacking the N17 domain (BACHD-ΔN17) show dramatically accelerated mHTT pathology exclusively in the nucleus, which is associated with HD-like transcriptionopathy. Interestingly, BACHD-ΔN17 mice manifest more overt disease-like phenotypes than the original BACHD mice, including body weight loss, movement deficits, robust striatal neuron loss, and neuroinflammation. Mechanistically, N17 is necessary for nuclear exclusion of small mHTT fragments that are part of nuclear pathology in HD. Together, our study suggests that N17 modifies nuclear pathogenesis and disease severity in HD mice by regulating subcellular localization of known nuclear pathogenic mHTT species