Lack of complex I activity in human cells carrying a mutation in MtDNA-encoded ND4 subunit is corrected by the Saccharomyces cerevisiae NADH-quinone oxidoreductase (NDI1) gene

The gene for the single subunit, rotenone-insensitive, and flavone-sensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae (NDI1) can completely restore the NADH dehydrogenase activity in mutant human cells that lack the essential mitochondrial DNA (mtDNA)-encoded subunit ND4. In particular, the NDI1 gene was introduced into the nuclear genome of the human 143B.TK cell line derivative C4T, which carries a homoplasmic frameshift mutation in the ND4 gene. Two transformants with a low or high level of expression of the exogenous gene were chosen for a detailed analysis. In these cells the corresponding protein is localized in mitochondria, its NADH-binding site faces the matrix compartment as in yeast mitochondria, and in perfect correlation with its abundance restores partially or fully NADH-dependent respiration that is rotenone-insensitive, flavone-sensitive, and antimycin A-sensitive. Thus the yeast enzyme has become coupled to the downstream portion of the human respiratory chain. Furthermore, the P:O ratio with malate/glutamate-dependent respiration in the transformants is approximately two-thirds of that of the wild-type 143B.TK cells, as expected from the lack of proton pumping activity in the yeast enzyme. Finally, whereas the original mutant cell line C4T fails to grow in medium containing galactose instead of glucose, the high NDI1-expressing transformant has a fully restored capacity to grow in galactose medium. The present observations substantially expand the potential of the yeast NDI1 gene for the therapy of mitochondrial diseases involving complex I deficiency

Terahertz active spatial filtering through optically tunable hyperbolic metamaterials

We theoretically consider infrared-driven hyperbolic metamaterials able to spatially filtering terahertz radiation. The metamaterial is a slab made of alternating semiconductor and dielectric layers whose homogenized uniaxial response, at terahertz frequencies, shows principal permittivities of different signs. The gap provided by metamaterial hyperbolic dispersion allows the slab to stop spatial frequencies within a bandwidth tunable by changing the infrared radiation intensity. We numerically prove the device functionality by resorting to full wave simulation coupled to the dynamics of charge carries photoexcited by infrared radiation in semiconductor layers.Comment: 3 pages, 4 figures. Submitted for publication on Applied Physics Letter

Towards a Video Consumer Leaning Spectrum: A Medium-Centric Approach

Purpose: As TV and digital video converge, there is a need to compare advertising effectiveness, advertising receptivity, and video consumption drivers in this new context. Considering the emerging viewing practices and underlying theories, this study examines the feasibility of the traditional notion of differentiating between lean-back (LB) and lean-forward (LF) media, and proposes a revised approach of addressing video consumption processes and associated advertising effectiveness implications. Methodology: An extensive, systematic literature review examines a total of 715 sources regarding current lean-back/lean-forward media research and alternative approaches as by (1) basic terminologies, (2) limitations of lean-back/lean-forward situations, (3) advertising effectiveness implications, (4) video-specific approaches. Findings/Contribution: Key differences between lean-back and lean-forward video consumption are presented. A conceptual integration of video ad receptivity/effectiveness drivers is proposed to guide future media and marketing research and practice. Video consumption today is no longer lean-back or lean-forward, but a “leaning spectrum” with two dimensions: leaning direction and leaning degree. Designing video content today requires focusing on consumption drivers and platform synergies for owning the “leaning spectrum”

Not Merely a Matter of Drawing Arrows: The Empirical Consequences of Measurement Model Specification and Recommendations for Practice

Understanding measurement model specification is especially important for hospitality research due to its cross-disciplinary nature and the prevalence of measures used in the field which are often central to the formative versus reflective debate (e.g., SERVQUAL, socioeconomic status). The current study contributes to this topic by providing empirically based prescriptive advice to drive better measurement model specification. Specifically, the decision-making procedures developed by this study can complement theoretical reasons for a model choice as well as help determine a correct model choice when theories are equivocal or non-existent. This study combines actual and simulated data to show that model fit statistics alone cannot determine which model specification is correct, but also that a correct measurement model will generate more accurate predictions within a model which in turn will offer more accurate managerial recommendations

Boston Hospitality Review: Winter 2019

TABLE OF CONTENTS: "Training: The Necessity of Error Management Training in the Hospitality Industry" by Priyanko Guchait; "Trends: Green Hotels: An Overview" by Minu Agarwal and Prashant Das; "Tourism: Panacea or peril? The implications of Neolocalism as a more intrusive form of tourism" by Makarand Mody and Kyle Koslowsky; "Restaurants: How Can Single-Unit Restaurants Strive for Powerful Online Presence?" by Leora Lanz and Jenna Berry; "Retention: Why Hoteliers Stay and Go: Future Oriented Thinking" by Sean McGinley; "Service Recovery: Failure is Not Fatal: Actionable Insights on Service Failure and Recovery for the Hospitality Industry" by Lisa C. Wan and Elisa Chan; "Research: A Detailed Study of the Expected and Actual Use of Hotel Amenities" by Chekitan S. Dev and Prateek Kumar

The Diversity of Core Halo Structure in the Fuzzy Dark Matter Model

In the fuzzy dark matter (FDM) model, gravitationally collapsed objects always consist of a solitonic core located within a virialised halo. Although various numerical simulations have confirmed that the collapsed structure can be described by a cored NFW like density profile, there is still disagreement about the relation between the core mass and the halo mass. To fully understand this relation, we have assembled a large sample of cored haloes based on both idealised soliton mergers and cosmological simulations with various box sizes. We find that there exists a sizeable dispersion in the core-halo mass relation that increases with halo mass, indicating that the FDM model allows cores and haloes to coexist in diverse configurations. We provide a new empirical equation for a core halo mass relation with uncertainties that can encompass all previously found relations in the dispersion, and emphasise that any observational constraints on the particle mass using a tight one-to-one core-halo mass relation should suffer from an additional uncertainty on the order of 50 % for halo masses $\ge 10^9 (8 \times 10^{-23} eV/ (mc^2))^{3/2} M_\odot$. We suggest that tidal stripping may be one of the effects contributing to the scatter in the relation

The Parkinson's Disease Associated LRRK2 Exhibits Weaker In Vitro Phosphorylation of 4E-BP Compared to Autophosphorylation

Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) are the most common cause of inherited Parkinson's disease (PD). LRRK2 is a multi-domain protein kinase containing a central catalytic core and a number of protein-protein interaction domains. An important step forward in the understanding of both the biology and the pathology of LRRK2 would be achieved by identification of its authentic physiological substrates. In the present study we examined phosphorylation of 4E-BP (eukaryotic initiation factor 4E (eIF4E)-binding protein), a recently proposed substrate for LRRKs. We found that LRRK2 is capable of phosphorylating 4E-BP in vitro. The PD related LRRK2-G2019S mutant was ∼2 fold more active than wild type protein. However, LRRK2 autophosphorylation was stronger than 4E-BP phosphorylation under conditions of molar excess of 4E-BP to LRRK2. We also tested three other kinases (STK3, MAPK14/p38α and DAPK2) and found that MAPK14/p38α could efficiently phosphorylate 4E-BP at the same site as LRRK2 in vitro. Finally, we did not see changes in 4E-BP phosphorylation levels using inducible expression of LRRK2 in HEK cell lines. We also found that MAPK14/p38α phosphorylates 4E-BP in transient overexpression experiments whereas LRRK2 did not. We suggest that increased 4E-BP phosphorylation reported in some systems may be related to p38-mediated cell stress rather than direct LRRK2 activity. Overall, our results suggest that 4E-BP is a relatively poor direct substrate for LRRK2

Circulating C-reactive protein and breast cancer risk – systematic literature review and meta-analysis of prospective cohort studies

We conducted a systematic literature review to explore the association between circulating C-reactive protein (CRP), a low-grade inflammation biomarker, and breast cancer risk. Relevant prospective studies in women were identified in PubMed and Web of Science until February 2015. Random-effects dose-response metaanalysis was conducted, overall and in post-menopausal women. Twelve out of 15 studies identified were included in the meta-analysis on any breast cancers (3,522 cases, 69,610 women) and nine on postmenopausal breast cancer (2,516 cases, 36,847 women). For each doubling of CRP concentration, a 7% (95% CI: 2%–12%) and 6% (95% CI: 1%–11%) increased risk was observed (I2=47% and 32%; P heterogeneity=0.04 and 0.17), respectively. The association was linear over most of the range of CRP concentrations. Positive associations remained in the studies that examined the exclusion of early years of follow-up. Associations were attenuated in studies adjusted for lifestyle factors, which partly explained the significant heterogeneity between studies in the overall analysis. On average, the associations in studies adjusted or not adjusted for body mass index were similar. Low-grade inflammation may have a role in breast cancer development. Additional prospective studies are needed to better understand confounding and effect modification from lifestyle factors