Superlattices have attracted great interest because their use may make it possible to modify the spectra of two-dimensional electron systems and, ultimately, create materials with tailored electronic ...properties. In previous studies (see, for example, refs 1-8), it proved difficult to realize superlattices with short periodicities and weak disorder, and most of their observed features could be explained in terms of cyclotron orbits commensurate with the superlattice. Evidence for the formation of superlattice minibands (forming a fractal spectrum known as Hofstadter's butterfly) has been limited to the observation of new low-field oscillations and an internal structure within Landau levels. Here we report transport properties of graphene placed on a boron nitride substrate and accurately aligned along its crystallographic directions. The substrate's moiré potential acts as a superlattice and leads to profound changes in the graphene's electronic spectrum. Second-generation Dirac points appear as pronounced peaks in resistivity, accompanied by reversal of the Hall effect. The latter indicates that the effective sign of the charge carriers changes within graphene's conduction and valence bands. Strong magnetic fields lead to Zak-type cloning of the third generation of Dirac points, which are observed as numerous neutrality points in fields where a unit fraction of the flux quantum pierces the superlattice unit cell. Graphene superlattices such as this one provide a way of studying the rich physics expected in incommensurable quantum systems and illustrate the possibility of controllably modifying the electronic spectra of two-dimensional atomic crystals by varying their crystallographic alignment within van der Waals heterostuctures.
Reduced sleep duration has been increasingly reported to predict obesity. However, timing and regularity of sleep may also be important. In this study, the cross-sectional association between ...objectively measured sleep patterns and obesity was assessed in two large cohorts of older individuals.
Wrist actigraphy was performed in 3053 men (mean age: 76.4 years) participating in the Osteoporotic Fractures in Men Study and 2985 women (mean age: 83.5 years) participating in the Study of Osteoporotic Fractures. Timing and regularity of sleep patterns were assessed across nights, as well as daytime napping.
Greater night-to-night variability in sleep duration and daytime napping were associated with obesity independent of mean nocturnal sleep duration in both men and women. Each 1 h increase in the standard deviation of nocturnal sleep duration increased the odds of obesity 1.63-fold (95% confidence interval: 1.31-2.02) among men and 1.22-fold (95% confidence interval: 1.01-1.47) among women. Each 1 h increase in napping increased the odds of obesity 1.23-fold (95% confidence interval: 1.12-1.37) in men and 1.29-fold (95% confidence interval: 1.17-1.41) in women. In contrast, associations between later sleep timing and night-to-night variability in sleep timing with obesity were less consistent.
In both older men and women, variability in nightly sleep duration and daytime napping were associated with obesity, independent of mean sleep duration. These findings suggest that characteristics of sleep beyond mean sleep duration may have a role in weight homeostasis, highlighting the complex relationship between sleep and metabolism.
Treatment of HCV infection by targeting microRNA Janssen, Harry L A; Reesink, Hendrik W; Lawitz, Eric J ...
New England journal of medicine/The New England journal of medicine,
05/2013, Letnik:
368, Številka:
18
Journal Article
Recenzirano
Odprti dostop
The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen is a locked nucleic ...acid-modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 in a highly stable heteroduplex, thereby inhibiting its function.
In this phase 2a study at seven international sites, we evaluated the safety and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection. The patients were randomly assigned to receive five weekly subcutaneous injections of miravirsen at doses of 3 mg, 5 mg, or 7 mg per kilogram of body weight or placebo over a 29-day period. They were followed until 18 weeks after randomization.
Miravirsen resulted in a dose-dependent reduction in HCV RNA levels that endured beyond the end of active therapy. In the miravirsen groups, the mean maximum reduction in HCV RNA level (log10 IU per milliliter) from baseline was 1.2 (P=0.01) for patients receiving 3 mg per kilogram, 2.9 (P=0.003) for those receiving 5 mg per kilogram, and 3.0 (P=0.002) for those receiving 7 mg per kilogram, as compared with a reduction of 0.4 in the placebo group. During 14 weeks of follow-up after treatment, HCV RNA was not detected in one patient in the 5-mg group and in four patients in the 7-mg group. We observed no dose-limiting adverse events and no escape mutations in the miR-122 binding sites of the HCV genome.
The use of miravirsen in patients with chronic HCV genotype 1 infection showed prolonged dose-dependent reductions in HCV RNA levels without evidence of viral resistance. (Funded by Santaris Pharma; ClinicalTrials.gov number, NCT01200420.).
Even though SN 2012cg is one of the best-studied Type Ia supernovae to date, the nature of its progenitor system has been debated in numerous studies. Specifically, it is difficult to reconcile ...recent claims of the detection of a ∼6 MS companion with recent deep, late-time flux limits. In this study we add three new constraints. (1) We analyze a new high-signal-to-noise, nebular-phase, Large Binocular Telescope/MODS spectrum of SN 2012cg and place an upper limit on the amount of low-velocity, solar-abundance material removed from a possible companion of . (2) We use Swift X-ray observations to constrain the pre-explosion mass-loss rate to be for . (3) We carefully reanalyze a prediscovery MASTER image, and with published light curves of SN 2012cg we estimate the time of first light and conservatively constrain the radius of a Roche-lobe overflowing companion to be . These observations disagree with a large nearby companion, and when considered with other studies of SN 2012cg's progenitor system, essentially rule out a non-degenerate companion.
The epidemiology of candidaemia varies between hospitals and geographic regions. Although there are many studies from Asia, a large-scale cross-sectional study across Asia has not been performed. We ...conducted a 12-month, laboratory-based surveillance of candidaemia at 25 hospitals from China, Hong Kong, India, Singapore, Taiwan and Thailand. The incidence and species distribution of candidaemia were determined. There were 1601 episodes of candidaemia among 1.2 million discharges. The overall incidence was 1.22 episodes per 1000 discharges and varied among the hospitals (range 0.16–4.53 per 1000 discharges) and countries (range 0.25–2.93 per 1000 discharges). The number of Candida blood isolates and the total number of fungal isolates were highly correlated among the six countries (R² = 0.87) and 25 hospitals (R² = 0.77). There was a moderate correlation between incidence of candidaemia and the intensive care unit (ICU)/total bed ratio (R² = 0.47), although ICUs contributed to only 23% of candidaemia cases. Of 1910 blood isolates evaluated, Candida albicans was most frequently isolated (41.3%), followed by Candida tropicalis (25.4%), Candida glabrata (13.9%) and Candida parapsilosis (12.1%). The proportion of C. tropicalis among blood isolates was higher in haemato-oncology wards than others wards (33.7% versus 24.5%, p 0.0058) and was more likely to be isolated from tropical countries than other Asian countries (46.2% versus 18.9%, p 0.04). In conclusion, the ICU settings contribute, at least in part, to the incidence variation among hospitals. The species distribution is different from Western countries. Both geographic and healthcare factors contribute to the variation of species distribution.
To study the incidence of sepsis and neonatal intensive care unit (NICU) costs as a function of the human milk (HM) dose received during the first 28 days post birth for very low birth weight (VLBW) ...infants.
Prospective cohort study of 175 VLBW infants. The average daily dose of HM (ADDHM) was calculated from daily nutritional data for the first 28 days post birth (ADDHM-Days 1-28). Other covariates associated with sepsis were used to create a propensity score, combining multiple risk factors into a single metric.
The mean gestational age and birth weight were 28.1 ± 2.4 weeks and 1087 ± 252 g, respectively. The mean ADDHM-Days 1-28 was 54 ± 39 ml kg(-1) day(-1) (range 0-135). Binary logistic regression analysis controlling for propensity score revealed that increasing ADDHM-Days 1-28 was associated with lower odds of sepsis (odds ratio 0.981, 95% confidence interval 0.967-0.995, P=0.008). Increasing ADDHM-Days 1-28 was associated with significantly lower NICU costs.
A dose-response relationship was demonstrated between ADDHM-Days 1-28 and a reduction in the odds of sepsis and associated NICU costs after controlling for propensity score. For every HM dose increase of 10 ml kg(-1) day(-1), the odds of sepsis decreased by 19%. NICU costs were lowest in the VLBW infants who received the highest ADDHM-Days 1-28.
High concentrations of potentially toxic elements (PTEs) in potable water can cause severe human health disorders. Present study examined the fitness of groundwater for drinking purpose based on the ...occurrence of nine PTEs in a heavy pilgrim and tourist influx region of the Garhwal Himalaya, India. The concentrations of analyzed PTEs in groundwater were observed in the order of Zn > Mn > As > Al > Cu > Cr > Se > Pb > Cd. Apart from Mn and As, other PTEs were within the corresponding guideline values. Spatial maps were produced to visualize the distribution of the PTEs in the area. Estimated water pollution indices and non-carcinogenic risk indicated that the investigated groundwater is safe for drinking purpose, as the hazard index was < 1 for all the water samples. Assessment of the cancer risk of Cr, As, Cd, and Pb also indicated low health risks associated with groundwater use, as the values were within the acceptable range of ≤ 1 × 10
to 1 × 10
. Multivariate statistical analyses were used to describe the various possible geogenic and anthropogenic sources of the PTEs in the groundwater resources although the contamination levels of the PTEs were found to pose no serious health risk. However, the present study recommends to stop the discharge of untreated wastewater and also to establish cost-effective as well as efficient water treatment facility nearby the study area. Present work's findings are vital as they may protect the health of the massive population from contaminated water consumption. Moreover, it can help the researchers, governing authorities and water supplying agencies to take prompt and appropriate decisions for water security.