Selective-Area Growth of Heavily \u3cem\u3en\u3c/em\u3e–Doped GaAs Nanostubs on Si(001) by Molecular Beam Epitaxy

Using an aspect ratio trapping technique, we demonstrate molecular beam epitaxy of GaAs nanostubs on Si(001) substrates. Nanoholes in a SiO2 mask act as a template for GaAs-on-Si selective-area growth(SAG) of nanostubs 120 nm tall and ≤100 nm in diameter. We investigate the influence of growthparameters including substrate temperature and growth rate on SAG. Optimizing these parameters results in complete selectivity with GaAsgrowth only on the exposed Si(001). Due to the confined-geometry, strain and defects in the GaAs nanostubs are restricted in lateral dimensions, and surface energy is further minimized. We assess the electrical properties of the selectively grownGaAs nanostubs by fabricating heterogeneous p+–Si/n+–GaAs p–n diodes

REST-FRAME UV SINGLE-EPOCH BLACK HOLE MASS ESTIMATES of LOW-LUMINOSITY AGNs at INTERMEDIATE REDSHIFTS

The ability to accurately derive black hole (BH) masses at progressively higher redshifts and over a wide range of continuum luminosities has become indispensable in the era of large-area extragalactic spectroscopic surveys. In this paper, we present an extension of existing comparisons between rest-frame UV and optical virial BH mass estimators to intermediate redshifts and luminosities comparable to the local Hβ reverberation-mapped active galactic nuclei (AGNs). We focus on the Mg ii, C iv, and C iii] broad emission lines and compare them to both Hα and Hβ. We use newly acquired near-infrared spectra from the Fiber-fed Multi-object Spectrograph instrument on the Subaru telescope for 89 broad-lined AGNs at redshifts between 0.3 and 3.5, complemented by data from the AGES survey. We employ two different prescriptions for measuring the emission line widths and compare the results. We confirm that Mg ii shows a tight correlation with Hα and Hβ, with a scatter of ~0.25 dex. The C iv and C iii] estimators, while showing larger scatter, are viable virial mass estimators after accounting for a trend with the UV-to-optical luminosity ratio. We find an intrinsic scatter of ~0.37 dex between Balmer and carbon virial estimators by combining our data set with previous high redshift measurements. This updated comparison spans a total of three decades in BH mass. We calculate a virial factor for C iv/C iii] $\mathrm{log}{f}_{{\rm{C}}{\rm{IV}}/{\rm{C}}{\rm{III}}]}=0.87$ with an estimated systematic uncertainty of ~0.4 dex and find excellent agreement between the local reverberation mapped AGN sample and our high-z sample

Space Telescope and Optical Reverberation Mapping Project. VII. Understanding the Ultraviolet Anomaly in NGC 5548 with X-Ray Spectroscopy

During the Space Telescope and Optical Reverberation Mapping Project observations of NGC 5548, the continuum and emission-line variability became decorrelated during the second half of the six-month-long observing campaign. Here we present Swift and Chandra X-ray spectra of NGC 5548 obtained as part of the campaign. The Swift spectra show that excess flux (relative to a power-law continuum) in the soft X-ray band appears before the start of the anomalous emission-line behavior, peaks during the period of the anomaly, and then declines. This is a model-independent result suggesting that the soft excess is related to the anomaly. We divide the Swift data into on- and off-anomaly spectra to characterize the soft excess via spectral fitting. The cause of the spectral differences is likely due to a change in the intrinsic spectrum rather than to variable obscuration or partial covering. The Chandra spectra have lower signal-to-noise ratios, but are consistent with the Swift data. Our preferred model of the soft excess is emission from an optically thick, warm Comptonizing corona, the effective optical depth of which increases during the anomaly. This model simultaneously explains all three observations: the UV emission-line flux decrease, the soft-excess increase, and the emission-line anomaly

A review of symptomatic leg length inequality following total hip arthroplasty

Leg length inequality (LLI) following total hip replacement is a complication which features increasingly in the recent literature. The definition of LLI is complicated by lack of consensus regarding radiological measurement, clinical measurement and the incomplete relationship between LLI and associated symptoms. This paper reviews 79 reports relating to LLI post hip replacement, detailing definitions and classification and highlighting patient populations prone to symptomatic LLI. While there is no universal definition of LLI, there is a broad consensus that less than 10 mm of difference on AP view plain radiographs is clinically acceptable. There are few techniques described that consistently produce a postoperative LLI of less than this magnitude. Where postoperative LLI exists, lengthening appears to cause more problems than shortening. In cases of mild LLI, non-surgical management produces adequate outcomes in the majority of cases, with functional LLI cases doing better than those with true LLI. Operative correction is effective in half of cases, even where nerve palsy is present, and remains an important option of last resort. Poor outcomes in patients with LLI may be minimised if individuals at risk are identified and counselled appropriately

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism