Physics design point of high-field stellarator reactors

The ongoing development of electromagnets based on High Temperature Superconductors has led to the conceptual exploration of high-magnetic-field fusion reactors of the tokamak type, operating at on-axis fields above 10 T. In this work we explore the consequences of the potential future availability of high-field three-dimensional electromagnets on the physics design point of a stellarator reactor. We find that, when an increase in the magnetic field strength $B$ is used to maximally reduce the device linear size $R\sim B^{-4/3}$ (with otherwise fixed magnetic geometry), the physics design point is largely independent of the chosen field strength/device size. A similar degree of optimization is to be imposed on the magnetohydrodynamic, transport and fast ion confinement properties of the magnetic configuration of that family of reactor design points. Additionally, we show that the family shares an invariant operation map of fusion power output as a function of the auxiliary power and relative density variation. The effects of magnetic field over-engineering and the $R(B)$ scaling of design points with constant neutron wall loading are also inspected. In this study we use geometric parameters characteristic of the \emph{helias} reactor, but most results apply to other stellarator configurations.

The Dynamics of SARS-CoV-2 Infectivity with Changes in Aerosol Microenvironment

Understanding the factors that influence the airborne survival of viruses such as SARSCoV2 in aerosols is important for identifying routes of transmission and the value of various mitigation strategies for preventing transmission. We present measurements of the stability of SARSCoV2 in aerosol droplets (5 to 10 micrometres equilibrated radius) over timescales spanning from 5 seconds to 20 minutes using a novel instrument to probe survival in a small population of droplets (typically 5-10) containing ~1 virus/droplet. Measurements of airborne infectivity change are coupled with a detailed physicochemical analysis of the airborne droplets containing the virus. A decrease in infectivity to 10 % of the starting value was observable for SARS-CoV-2 over 20 minutes, with a large proportion of the loss occurring within the first 5 minutes after aerosolisation. The initial rate of infectivity loss was found to correlate with physical transformation of the equilibrating droplet; salts within the droplets crystallise at RHs below 50% leading to a near instant loss of infectivity in 50 to 60% of the virus. However, at 90% RH the droplet remains homogenous and aqueous, and the viral stability is sustained for the first 2 minutes, beyond which it decays to only 10% remaining infectious after 10 minutes. The loss of infectivity at high RH is consistent with an elevation in the pH of the droplets, caused by volatilisation of CO2 from bicarbonate buffer within the droplet. Three different variants of SARS-CoV-2 were compared and found to have a similar degree of airborne stability at both high and low RH.

Multinationals, Capital Export, and the Inclusive Development Debate in Developing Countries: The Nigerian Insight

In this paper, we employed a blend of multiple and historical case study design, and a mix of institutional, behavioral, resource-based, and multinational theories, to examine the nature of multinational companies’ (MNC) engagements in local economic development and capital export practices in an African context. Evidence from our Nigerian case analysis (FrieslandCampina, Nigerian Breweries Plc. and Dangote Cement) confirms the proposition that, faced with a similar degree of uncertainty and constrained institutional environment and laying claims to differing sources of competitive advantage, both local and foreign MNCs would repatriate profits and limit exposures to local value chains (LVCs) mainly as a strategy for mitigating country risks and preserving corporate value. Such limited exposures detach MNCs, especially the foreign ones, from the LVCs, and by doing so push them to deeper reliance on the global value chains (GVCs). Linking local businesses to the GVCs is central in the inclusive development (ID) debate essentially because it allows for the redistribution of economic benefits, helps in building a complementary (rather than competitive) relationship between MNCs and local businesses, and facilitates local businesses’ access to international markets. We, therefore, recommend that in pursuit of the inclusive and sustainable development projects in Africa, industrial policies need to be tailored toward stabilizing the policy environment, protecting investments from risk of expropriation, and incentivizing MNCs’ participation in the LVCs.

Unsupervised high-frequency smartphone-based cognitive assessments are reliable, valid, and feasible in older adults at risk for Alzheimer disease.

Smartphones have the potential for capturing subtle changes in cognition that characterize preclinical Alzheimer disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on principles from ecological momentary assessment (EMA) and administers brief tests of associative memory, processing speed, and working memory up to 4 times per day over 7 consecutive days. ARC was designed to be administered unsupervised using participants’ personal devices in their everyday environments. We evaluated the reliability and validity of ARC in a sample of 268 cognitively normal older adults (ages 65-97) and 22 individuals with very mild dementia (ages 61-88). Participants completed at least one 7-day cycle of ARC testing and conventional cognitive assessments; most also completed cerebrospinal fluid, amyloid and tau PET, and structural MRI studies. First, results indicated that ARC tasks were reliable as between person reliability across the 7-day cycle and test-retest reliabilities at 6-month and 1-year follow-ups all exceeded 0.85. Second, ARC demonstrated construct validity as evidenced by correlations with conventional cognitive measures (r = 0.53 between composite scores). Third, ARC measures correlated with AD biomarker burden at baseline to a similar degree as conventional cognitive measures. Finally, the intensive 7-day cycle indicated that ARC was feasible (86.50% approached chose to enroll), well tolerated (80.42% adherence, 4.83% dropout), and was rated favorably by older adult participants. Overall, the results suggest that ARC is reliable and valid and represents a feasible tool for assessing cognitive changes associated with the earliest stages of AD.

Landscape of homologous recombination deficiencies in solid tumours: analyses of two independent genomic datasets

Background DNA repair deficiencies are characteristic of cancer and homologous recombination deficiency (HRD) is the most common. HRD sensitizes tumour cells to PARP inhibitors so it is important to understand the landscape of HRD across different solid tumour types. Methods Germline and somatic BRCA mutations in breast and ovarian cancers were evaluated using sequencing data from The Cancer Genome Atlas (TCGA) database. Secondly, a larger independent genomic dataset was analysed to validate the TCGA results and determine the frequency of germline and somatic mutations across 15 different candidate homologous recombination repair (HRR) genes, and their relationship with the genetic events of bi-allelic loss, loss of heterozygosity (LOH) and tumour mutation burden (TMB). Results Approximately one-third of breast and ovarian cancer BRCA mutations were somatic. These showed a similar degree of bi-allelic loss and clinical outcomes to germline mutations, identifying potentially 50% more patients that may benefit from precision treatments. HRR mutations were present in sizable proportions in all tumour types analysed and were associated with high TMB and LOH scores. We also identified numerous BRCA reversion mutations across all tumour types. Conclusions Our results will facilitate future research into the efficacy of precision oncology treatments, including PARP and immune checkpoint inhibitors.

Comparison of National Innovation Systems in the European Union Countries

The effective operation of national innovation systems can be a source of many opportunities, but it cannot be forgotten that innovation in itself may mean limiting but also generating various types of risks for the functioning of the local market. The main aim of the article is to present the concept and classification of national innovation systems in the world and to try to answer whether the type of NIS determines the level of innovation of the economies of the European Union countries. The following research thesis was formulated in the study: the type of National Innovation System determines a certain level of innovation in the economy of an European Union country, i.e., in countries belonging to a developed NIS, the level of innovation of the economy is higher than in countries belonging to developing systems. The results of the analysis confirm the research thesis. In the empirical part, the level of innovation in the European Union countries was assessed using the synthetic measure of development (SMD) by Z. Hellwig. Based on the obtained values of the synthetic measure of development (innovation), a ranking of the innovation of the economies of the EU countries was compiled and groups of countries with a similar degree of innovation in the economy were distinguished. The developed ranking of the European Union countries was compared with the NSI classification presented in the theoretical part of the article. The study covered 2010 and 2019.

New Strategies to Promote Macrophage Cholesterol Efflux

The capacity of macrophages to dispose of cholesterol deposited in the atherosclerotic plaque depends on their ability to activate cholesterol efflux pathways. To develop athero-protective therapies aimed at promoting macrophage cholesterol efflux, cholesterol metabolism in THP-1 monocyte-derived macrophages has been extensively studied, but the intrinsic sensitivity of monocytes and the lack of a standardized procedure to differentiate THP-1 monocytes into macrophages have made it difficult to utilize THP-1 macrophages in the same or similar degree of differentiation across studies. The variability has resulted in lack of understanding of how the differentiation affects cholesterol metabolism, and here we review and investigate the effects of THP-1 differentiation on cholesterol efflux. The degree of THP-1 differentiation was inversely associated with ATP binding cassette A1 (ABCA1) transporter-mediated cholesterol efflux. The differentiation-associated decrease in ABCA1-mediated cholesterol efflux occurred despite an increase in ABCA1 expression. In contrast, DSC1 expression decreased during the differentiation. DSC1 is a negative regulator of the ABCA1-mediated efflux pathway and a DSC1-targeting agent, docetaxel showed high potency and efficacy in promoting ABCA1-mediated cholesterol efflux in THP-1 macrophages. These data suggest that pharmacological targeting of DSC1 may be more effective than increasing ABCA1 expression in promoting macrophage cholesterol efflux. In summary, the comparison of THP-1 macrophage subtypes in varying degrees of differentiation provided new insights into cholesterol metabolism in macrophages and allowed us to identify a viable target DSC1 for the promotion of cholesterol efflux in differentiated macrophages. Docetaxel and other pharmacological strategies targeting DSC1 may hold significant potential for reducing atherogenic cholesterol deposition.

A Role for Synaptonemal Complex in Meiotic Mismatch Repair

A large subset of meiotic recombination intermediates form within the physical context of synaptonemal complex (SC), but the functional relationship between SC structure and homologous recombination remains obscure. Our prior analysis of strains deficient for SC central element proteins demonstrated that tripartite SC is dispensable for interhomolog recombination in S. cerevisiae. Here we report that while dispensable for recombination per se, SC proteins promote efficient mismatch repair at interhomolog recombination sites. Failure to repair mismatches within heteroduplex-containing meiotic recombination intermediates leads to genotypically sectored colonies (post meiotic segregation events). We discovered increased post-meiotic segregation at THR1 in cells lacking Ecm11 or Gmc2, or in the SC-deficient but recombination-proficient zip1[Δ21-163] mutant. High-throughput sequencing of octad meiotic products furthermore revealed a genome-wide increase in recombination events with unrepaired mismatches in ecm11 mutants relative to wild type. Meiotic cells missing Ecm11 display longer gene conversion tracts, but tract length alone does not account for the higher frequency of unrepaired mismatches. Interestingly, the per-nucleotide mismatch frequency is elevated in ecm11 when analyzing all gene conversion tracts, but is similar between wild type and ecm11 if considering only those events with unrepaired mismatches. Thus, in both wild type and ecm11 strains a subset of recombination events is susceptible to a similar degree of inefficient mismatch repair, but in ecm11 mutants a larger fraction of events fall into this inefficient repair category. Finally, we observe elevated post-meiotic segregation at THR1 in mutants with a dual deficiency in MutSγ crossover recombination and SC assembly, but not in the mlh3 mutant, which lacks MutSγ crossovers but has abundant SC. We propose that SC structure promotes efficient mismatch repair of joint molecule recombination intermediates, and that absence of SC is the molecular basis for elevated post-meiotic segregation in both MutSγ crossover-proficient (ecm11, gmc2) and MutSγ crossover-deficient (msh4, zip3) strains.

Proteogenomic analysis of aneuploidy reveals divergent types of gene expression regulation across cellular pathways

How cells control gene expression is a fundamental question. The relative contribution of protein-level and transcript-level regulation to this process remains unclear. Here we perform a proteogenomic analysis of tumors and untransformed cells containing somatic copy number alterations (SCNAs). By revealing how cells regulate transcript and protein abundances of SCNA genes, we provide insights into the rules of gene regulation. While gene compensation mainly occurs at the protein level across tumor types, genes gained or lost show surprisingly low protein compensation in lung and high RNA compensation in colon cancer. Protein complex genes have a strong protein-level regulation while non-complex genes have a strong transcript-level regulation. Exceptions are plasma membrane protein complexes showing a very low protein-level regulation. Strikingly, we find a strong negative association between the degree of transcript-level and protein-level regulation across genes and pathways. Moreover, genes participating in the same pathway show similar degree of transcript- and protein-level regulation. Pathways including translation, splicing and mitochondrial function show a stronger protein-level regulation while cell adhesion and migration pathways show a stronger transcript-level regulation. These results suggest that the evolution of gene regulation is shaped by functional constraints and that many cellular pathways tend to evolve a predominant mechanism of gene regulation, possibly due to energetic constraints.

COMPARING THE PRIVACY VS DAYLIGHT COMPROMISE FOR DIFFERENT WINDOW COVERINGS

Cultural factors in Libya (and other Muslim countries) require female privacy to be maintained. Outside the home, females must wear clothing that reveals only the face and hands. When inside the home and located near windows, a similar degree of clothing cover, or, window screening, is required. This reduces exposure to natural daylight, with resultant reduction in health benefits of daylight. We are therefore investigating the degree to which window privacy devices offer sufficient privacy to permit relaxed clothing in the home, and whether this leads to an increased daylight exposure. Two window coverings were tested, horizontal blinds and frosted glass, varying the free area and degree of frosting respectively. The degree of privacy offered was operationalised by identification of the clothing level worn by a target behind the window screen, the aim being to reduce this to a chance level. For horizontal blinds, the free area must be reduced to 3% to maintain sufficient privacy, which is unlikely to permit sufficient daylight to offset the wearing of relaxed clothing. While a high degree of frosting is required for a similar level of privacy, this may permit more daylight.