Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research ...efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD.
Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process of homologous recombination, ...whereby DNA double-strand breaks are introduced into the genome and are subsequently repaired to generate either noncrossovers or crossovers. Although homologous recombination is essential for chromosome pairing during prophase I, the resulting crossovers are critical for maintaining homolog interactions and enabling accurate segregation at the first meiotic division. Thus, the placement, timing, and frequency of crossover formation must be exquisitely controlled. In this review, we discuss the proteins involved in crossover formation, the process of their formation and designation, and the rules governing crossovers, all within the context of the important landmarks of prophase I. We draw together crossover designation data across organisms, analyze their evolutionary divergence, and propose a universal model for crossover regulation.
Piezoelectrics with negative longitudinal piezoelectric coefficients will contract in the direction of an applied electric field. Such piezoelectrics are thought to be rare, but there is no ...fundamental physics preventing the realization of negative longitudinal piezoelectric effect in a single-phase material. Using first-principles calculations, we demonstrate that several hexagonal ABC ferroelectrics possess significant negative longitudinal piezoelectric effects. The data mining of a first-principles-based database of piezoelectrics reveals that this effect is a general phenomenon. The origin of this unusual piezoelectric response relies on the strong ionic bonds associated with small effective charges and rigid potential energy surfaces. Moreover, ferroelectrics with negative longitudinal piezoelectric coefficients show anomalous pressure-enhanced ferroelectricity. Our results offer design principles to aid the search for new piezoelectrics for novel electromechanical device applications.
WHAT PRIVACY IS FOR Cohen, Julie E.
Harvard law review,
05/2013, Letnik:
126, Številka:
7
Journal Article
Recenzirano
Privacy has an image problem. Over and over again, regardless of the forum in which it is debated, it is cast as old-fashioned at best and downright harmful at worst - antiprogressive, overly costly, ...and inimical to the welfare of the body politic. Privacy advocates resist this framing but seem unable either to displace it or to articulate a comparably urgent description of privacy's importance. No single meme or formulation of privacy's purpose has emerged around which privacy advocacy might coalesce. Pleas to "balance" the harms of privacy invasion against the asserted gains lack visceral force.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, PRFLJ, SAZU, UILJ, UKNU, UL, UM, UPUK
A molecule or larger body is chiral if it cannot be superimposed on its mirror image (enantiomer). Electromagnetic fields may be chiral, too, with circularly polarized light (CPL) as the paradigmatic ...example. A recently introduced measure of the local degree of chiral dissymmetry in electromagnetic fields suggested the existence of optical modes more selective than circularly polarized plane waves in preferentially exciting single enantiomers in certain regions of space. By probing induced fluorescence intensity, we demonstrated experimentally an 11-fold enhancement over CPL in discrimination of the enantiomers of a biperylene derivative by precisely sculpted electromagnetic fields. This result, which agrees to within 15% with theoretical predictions, establishes that optical chirality is a fundamental and tunable property of light, with possible applications ranging from plasmonic sensors to absolute asymmetric synthesis.
This review highlights the evidence-based data to support current best management practices for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Current ...limitations and areas of emerging therapeutics are also emphasized. The cornerstone of palliation for patients with R/M HNSCC is a platinum-based backbone. Platinum doublets induce higher response rates than single agents but do not demonstrate a survival advantage and are associated with increased toxicity. The only regimen to demonstrate survival superiority is platinum, fluorouracil, and cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR). EGFR inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only modest success in R/M HNSCC, illustrating the importance of identifying predictive biomarkers and finding ways to overcome mechanisms of resistance. Although phosphoinositide 3-kinase pathway alterations are present at a high rate in HNSCC, the identification of efficacious agents in patients with activating alterations has yet to be discovered. Immunotherapy represents an attractive treatment strategy for R/M HNSCC, with promising preliminary data from studies involving immune checkpoint blockade and toll-like receptor agonists. Human papillomavirus has a prognostic role in R/M disease; therefore, stratification of patients by human papillomavirus status in clinical trials is indicated. Although under-represented in clinical trials, elderly patients experience similar survival outcomes compared with younger patients, albeit with increased toxicity. Despite therapeutic advances, prognosis nonetheless remains poor for patients with R/M HNSCC. Enrollment of patients onto clinical trials to investigate novel therapeutics and identify predictive biomarkers is necessary to further refine and improve outcomes.
Antibacterial coatings based on hydrogen-bonded multilayers containing in situ synthesized Ag nanoparticles were created on planar surfaces and on magnetic colloidal particles. We report the ...antibacterial properties of these coatings, determined using a disk-diffusion (Kirby-Bauer) test, as a function of the film thickness and the concentration of Ag nanoparticles in the hydrogen-bonded multilayers. The zone of inhibition (ZoI) determined by the disk-diffusion test increases as the thickness of the multilayer film is increased. Results obtained for the values of the ZoI as a function of film thickness can be described adequately with a simple diffusion model (i.e., the square of the zone of inhibition (ZoI) depended linearly on the logarithm of the thickness of the silver-loaded films). This observation suggests that, in order to incrementally increase the ZoI, an exponentially increasing amount of Ag is required within the multilayers. In general, there was no statistically significant correlation between the zone of inhibition and the number of Ag loading and reduction cycles. The duration of sustained release of antibacterial Ag ions from these coatings, however, could be prolonged by increasing the total supply of zerovalent silver in the films via multiple loading and reduction cycles. These results indicate that the release of silver is controlled by an oxidation mechanism at the surface of the nanoparticles and that repeated loading and reduction of silver leads preferentially to growth of the existing silver nanoparticles in the film as opposed to nucleation of new Ag nanoparticles. We also show that magnetic microspheres coated with silver nanoparticle loaded hydrogen-bonded multilayer thin films can be used to deliver antibacterial agents to specific locations. The minimum inhibitory concentration (MIC) of nanocomposite coated microspheres was determined by the agar dilution technique: antibacterial magnetic microspheres with higher concentrations of Ag nanoparticles exhibited lower MIC values.
We measure the electrical resistivity of hcp iron up to ∼ 170 GPa and ∼ 3000 K using a four-probe van der Pauw method coupled with homogeneous flattop laser heating in a DAC, and compute its ...electrical and thermal conductivity by first-principles molecular dynamics including electron-phonon and electron-electron scattering. We find that the measured resistivity of hcp iron increases almost linearly with temperature, and is consistent with our computations. The results constrain the resistivity and thermal conductivity of hcp iron to ∼ 80 ± 5 μ Ω cm and ∼ 100 ± 10 W m−1 K−1, respectively, at conditions near the core-mantle boundary. Our results indicate an adiabatic heat flow of ∼ 10 ± 1 TW out of the core, supporting a present-day geodynamo driven by thermal and compositional convection.
PDF
