Double point contact in Quantum Hall Line Junctions

We show that multiple point contacts on a barrier separating two laterally coupled quantum Hall fluids induce Aharonov-Bohm (AB) oscillations in the tunneling conductance. These quantum coherence effects provide new evidence for the Luttinger liquid behavior of the edge states of quantum Hall fluids. For a two point contact, we identify coherent and incoherent regimes determined by the relative magnitude of their separation and the temperature. We analyze both regimes in the strong and weak tunneling amplitude limits as well as their temperature dependence. We find that the tunneling conductance should exhibit AB oscillations in the coherent regime, both at strong and weak tunneling amplitude with the same period but with different functional form.Comment: 4 pages, 3 figures; new version, edited text, 2 new references; figure 2 has been edited; new paragraph in page 1 and minor typos have been correcte

X-ray Imaging of Transplanar Liquid Transport Mechanisms in Single Layer Textiles

Understanding the penetration of liquids within textile fibers is critical for the development of next-generation smart textiles. Despite substantial research on liquid penetration in the plane of the textile, little is known about how the liquid penetrates in the thickness direction. Here we report a time-resolved high-resolution X-ray measurement of the motion of the liquid–air interface within a single layer textile, as the liquid is transported across the textile thickness following the deposition of a droplet. The measurement of the time-dependent position of the liquid meniscus is made possible by the use of ultrahigh viscosity liquids (dynamic viscosity from 10⁵ to 2.5 × 10⁶ times larger than water). This approach enables imaging due to the slow penetration kinetics. Imaging results suggest a three-stage penetration process with each stage being associated with one of the three types of capillary channels existing in the textile geometry, providing insights into the effect of the textile structure on the path of the three-dimensional liquid meniscus. One dimensional kinetics studies show that our data for the transplanar penetration depth Δ<i>x</i>_L vs time do not conform to a power law, and that the measured rate of penetration for long times is smaller than that predicted by Lucas–Washburn kinetics, challenging commonly held assumptions regarding the validity of power laws when applied to relatively thin textiles

Post-Craniotomy Pain in the Brain Tumor Patient: An Integrative Review

Aim To conduct an integrative review to examine evidence of pain and associated symptoms in adult (≥21 years of age), postcraniotomy, brain tumour patients hospitalized on intensive care units. Background Healthcare providers believe craniotomies are less painful than other surgical procedures. Understanding how postcraniotomy pain unfolds over time will help inform patient care and aid in future research and policy development. Design Systematic literature search to identify relevant literature. Information abstracted using the Theory of Unpleasant Symptoms’ concepts of influencing factors, symptom clusters and patient performance. Inclusion criteria were indexed, peer-reviewed, full-length, English-language articles. Keywords were ‘traumatic brain injury’, ‘pain, post-operative’, ‘brain injuries’, ‘postoperative pain’, ‘craniotomy’, ‘decompressive craniectomy’ and ‘trephining’. Data sources Medline, OVID, PubMed and CINAHL databases from 2000–2014. Review method Cooper's five-stage integrative review method was used to assess and synthesize literature. Results The search yielded 115 manuscripts, with 26 meeting inclusion criteria. Most studies were randomized, controlled trials conducted outside of the United States. All tested pharmacological pain interventions. Postcraniotomy brain tumour pain was well-documented and associated with nausea, vomiting and changes in blood pressure, and it impacted the patient's length of hospital stay, but there was no consensus for how best to treat such pain. Conclusion The Theory of Unpleasant Symptoms provided structure to the search. Postcraniotomy pain is experienced by patients, but associated symptoms and impact on patient performance remain poorly understood. Further research is needed to improve understanding and management of postcraniotomy pain in this population

Effectiveness of enhanced diabetes care to patients of South Asian ethnicity : the United Kingdom Asian Diabetes Study (UKADS) : a cluster randomised controlled trial

Background: Delivering high quality and evidence based healthcare to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive enhanced care package in UK general practice in improving cardiovascular risk factors in South Asian patients with type 2 diabetes. Methods: 21 inner city practices were randomised to intervention (enhanced practice nurse time, link worker and diabetes specialist nurse support) (n=868) or control (standard care) (n=618) groups. Prescribing algorithms with clearly defined targets were provided for all practices. Main outcome measures comprised changes in blood pressure, total cholesterol and glycaemic control (HbA1c) after 2 years. Findings: At baseline, groups were similar with respect to age, sex and cardiovascular risk factors. Comparing treatment groups, after adjustment for confounders, and clustering, differences in diastolic blood pressure (1.91mmHg, P=0.0001) and mean arterial pressure (1.36mmHg, P=0.0180) were significant. There were no significant differences between groups for total cholesterol or HbA1c. Economic analysis indicates the nurse-led intervention was not cost-effective. Across the whole study population systolic blood pressure, diastolic blood pressure and cholesterol decreased significantly by 4.9mmHg, 3.8mmHg and 0.45mmol/L respectively, but there was no change in HbA1c. Interpretation: Additional, although limited, benefits were observed from our culturally enhanced care package over and above the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to maximise healthcare outcomes in South Asian patients with diabetes

Drug repurposing for rare:progress and opportunities for the rare disease community

Repurposing is one of the key opportunities to address the unmet rare diseases therapeutic need. Based on cases of drug repurposing in small population conditions, and previous work in drug repurposing, we analyzed the most important lessons learned, such as the sharing of clinical observations, reaching out to regulatory scientific advice at an early stage, and public-private collaboration. In addition, current upcoming trends in the field of drug repurposing in rare diseases were analyzed, including the role these trends could play in the rare diseases’ ecosystem. Specifically, we cover the opportunities of innovation platforms, the use of real-world data, the use of artificial intelligence, regulatory initiatives in repurposing, and patient engagement throughout the repurposing project. The outcomes from these emerging activities will help progress the field of drug repurposing for the benefit of patients, public health and medicines development

Survey of the quality of experimental design, statistical analysis and reporting of research using animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria

The identification of informative genes from multiple datasets with increasing complexity

Background In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes. Results In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes. Conclusions We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events

Inter edge Tunneling in Quantum Hall Line Junctions

We propose a scenario to understand the puzzling features of the recent experiment by Kang and coworkers on tunneling between laterally coupled quantum Hall liquids by modeling the system as a pair of coupled chiral Luttinger liquid with a point contact tunneling center. We show that for filling factors $\nu\sim1$ the effects of the Coulomb interactions move the system deep into strong tunneling regime, by reducing the magnitude of the Luttinger parameter $K$, leading to the appearance of a zero-bias differential conductance peak of magnitude $G_t=Ke^2/h$ at zero temperature. The abrupt appearance of the zero bias peak as the filling factor is increased past a value $\nu^* \gtrsim 1$, and its gradual disappearance thereafter can be understood as a crossover controlled by the main energy scales of this system: the bias voltage $V$, the crossover scale $T_K$, and the temperature $T$. The low height of the zero bias peak $\sim 0.1e^2/h$ observed in the experiment, and its broad finite width, can be understood naturally within this picture. Also, the abrupt reappearance of the zero-bias peak for $\nu \gtrsim 2$ can be explained as an effect caused by spin reversed electrons, \textit{i. e.} if the 2DEG is assumed to have a small polarization near $\nu\sim2$. We also predict that as the temperature is lowered $\nu^*$ should decrease, and the width of zero-bias peak should become wider. This picture also predicts the existence of similar zero bias peak in the spin tunneling conductance near for $\nu \gtrsim 2$.Comment: 17 pages, 8 figure

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice