Infrared Metasurfaces Created with Off-Normal Incidence Microsphere Photolithography

Fabricating metasurfaces over large areas at low costs remains a critical challenge to their practical implementation. This paper reports on the use of microsphere photolithography (MPL) to create infrared metasurfaces by changing the angle-of-incidence of the illumination to steer the photonic jet. The displacement of the photonic jet is shown to scale with the diameter of the microsphere while the exposure dose scales with the square of the microsphere diameter. This process is robust in the presence of local defects in the microsphere lattice. The paper demonstrates patterning split ring resonators and tripole based metasurfaces using MPL, which are fabricated and characterized with FTIR. The combination of bottom-up and top-down approaches in off-normal incidence microsphere photolithography technique provides cost-effective, flexible, and high-throughput fabrication of infrared metasurfaces

Experimental Investigation of Condensation Phenomenon on Hydrophilic and Hydrophobic Titanium (Ti) Pillared Glass Surfaces

Atmospheric condensation is very important for multiple practical applications such as heat transfer, aerospace, and water harvesting etc. Surfaces below the dew point temperature, heterogeneously nucleate water droplets on the surfaces. Gibbs free energy of heterogeneous nucleation barrier for a condensed droplet on a rough surface changes significantly with the change of humidity content. The influence of environmental factors and substrate characteristics (topology, surface chemistry, and substrate temperature) on atmospheric condensation is very important to elucidate the droplet shape and wetting state. Condensation from the humid air has been studied on Titanium (Ti) pillars and Teflon© coated Ti pillared glass surfaces in order to reveal the condensate harvesting and dropwise condensation applications

Mechanistic Insights into Hsp104 Potentiation

Potentiated variants of Hsp104, a protein disaggregase from yeast, can dissolve protein aggregates connected to neurodegenerative diseases such as Parkinson disease and amyotrophic lateral sclerosis. However, the mechanisms underlying Hsp104 potentiation remain incompletely defined. Here, we establish that 2–3 subunits of the Hsp104 hexamer must bear an A503V potentiating mutation to elicit enhanced disaggregase activity in the absence of Hsp70. We also define the ATPase and substrate-binding modalities needed for potentiated Hsp104A503V activity in vitro and in vivo. Hsp104A503V disaggregase activity is strongly inhibited by the Y257A mutation that disrupts substrate binding to the nucleotide-binding domain 1 (NBD1) pore loop and is abolished by the Y662A mutation that disrupts substrate binding to the NBD2 pore loop. Intriguingly, Hsp104A503V disaggregase activity responds to mixtures of ATP and adenosine 5′-(γ-thio)-triphosphate (a slowly hydrolyzable ATP analogue) differently from Hsp104. Indeed, an altered pattern of ATP hydrolysis and altered allosteric signaling between NBD1 and NBD2 are likely critical for potentiation. Hsp104A503V variants bearing inactivating Walker A or Walker B mutations in both NBDs are inoperative. Unexpectedly, however, Hsp104A503V retains potentiated activity upon introduction of sensor-1 mutations that reduce ATP hydrolysis at NBD1 (T317A) or NBD2 (N728A). Hsp104T317A/A503V and Hsp104A503V/N728A rescue TDP-43 (TAR DNA-binding protein 43), FUS (fused in sarcoma), and α-synuclein toxicity in yeast. Thus, Hsp104A503V displays a more robust activity that is unperturbed by sensor-1 mutations that greatly reduce Hsp104 activity in vivo. Indeed, ATPase activity at NBD1 or NBD2 is sufficient for Hsp104 potentiation. Our findings will empower design of ameliorated therapeutic disaggregases for various neurodegenerative diseases

Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients

Chronic hepatitis B; HBeAg status; Viral genome variationHepatitis B crónica; Estado de HBeAg; Variación del genoma viralHepatitis B crònica; Estat de HBeAg; Variació del genoma viralDespite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequencing of viral samples from patients chronically infected with HBV to investigate the association between viral genome variation and patients’ clinical characteristics. We discovered novel viral variants strongly associated with viral load and HBeAg status. Patients with viral variants C1817T and A1838G had viral loads nearly three orders of magnitude lower than patients without those variants. These patients consequently experienced earlier viral suppression while on treatment. Furthermore, we identified novel variants that either independently or in combination with precore mutation G1896A were associated with the transition from HBeAg positive to the negative phase of infection. These observations are consistent with the hypothesis that mutation of the HBeAg open reading frame is an important factor driving CHB patient’s HBeAg status. This analysis provides a detailed picture of HBV genetic variation in the largest patient cohort to date and highlights the diversity of plausible molecular mechanisms through which viral variation affects clinical phenotype

Central obesity as a precursor to the metabolic syndrome in the AusDiab study and Mauritius

Evidence from epidemiologic studies that central obesity precedes future metabolic change and does not occur concurrently with the appearance of the blood pressure, glucose, and lipid abnormalities that characterize the metabolic syndrome (MetS) has been lacking. Longitudinal surveys were conducted in Mauritius in 1987, 1992, and 1998, and in Australia in 2000 and 2005 (AusDiab). This analysis included men and women (aged 25 years) in three cohorts: AusDiab 2000&ndash;2005 (n = 5,039), Mauritius 1987&ndash;1992 (n = 2,849), and Mauritius 1987&ndash;1998 (n = 1,999). MetS components included waist circumference, systolic blood pressure, fasting and 2-h postload plasma glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and homeostasis model assessment of insulin sensitivity (HOMA-S) (representing insulin sensitivity). Linear regression was used to determine which baseline components predicted deterioration in other MetS components over 5 years in AusDiab and 5 and 11 years in Mauritius, adjusted for age, sex, and ethnic group. Baseline waist circumference predicted deterioration (P &lt; 0.01) in four of the other six MetS variables tested in AusDiab, five of six in Mauritius 1987&ndash;1992, and four of six in Mauritius 1987&ndash;1998. In contrast, an increase in waist circumference between baseline and follow-up was only predicted by insulin sensitivity (HOMA-S) at baseline, and only in one of the three cohorts. These results suggest that central obesity plays a central role in the development of the MetS and appears to precede the appearance of the other MetS components.<br /

Strengthening care and research for women's cancers in Sub-Saharan Africa

Highlights • The burden of gynecologic cancers in low resource settings is overwhelming. • Areas with the highest needs have few human resources and limited infrastructure. • Cancer specialists can best help by leveraging ongoing work to assist local leaders

Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents.

BACKGROUND: Depression in adolescence is debilitating with high recurrence in adulthood, yet its pathophysiological mechanism remains enigmatic. To examine the interaction between emotion, cognition and treatment, functional brain responses to sad and happy distractors in an affective go/no-go task were explored before and after Cognitive Behavioural Therapy (CBT) in depressed female adolescents, and healthy participants. METHODS: Eighty-two Depressed and 24 healthy female adolescents, aged 12-17 years, performed a functional magnetic resonance imaging (fMRI) affective go/no-go task at baseline. Participants were instructed to withhold their responses upon seeing happy or sad words. Among these participants, 13 patients had CBT over approximately 30 weeks. These participants and 20 matched controls then repeated the task. RESULTS: At baseline, increased activation in response to happy relative to neutral distractors was observed in the orbitofrontal cortex in depressed patients which was normalised after CBT. No significant group differences were found behaviourally or in brain activation in response to sad distractors. Improvements in symptoms (mean: 9.31, 95% CI: 5.35-13.27) were related at trend-level to activation changes in orbitofrontal cortex. LIMITATIONS: In the follow-up section, a limited number of post-CBT patients were recruited. CONCLUSIONS: To our knowledge, this is the first fMRI study addressing the effect of CBT in adolescent depression. Although a bias toward negative information is widely accepted as a hallmark of depression, aberrant brain hyperactivity to positive distractors was found and normalised after CBT. Research, assessment and treatment focused on positive stimuli could be a future consideration. Moreover, a pathophysiological mechanism distinct from adult depression may be suggested and awaits further exploration.The study was funded by the Medial Research Council (grant: G0802226). The IMPACT clinical trial was funded by the NHS Health Technology Assessment (HTA) Programme, Central Manchester and Manchester Children's University Hospitals NHS Trust, and the Cambridge and Peterborough Mental Health Trust. Additional support was provided by the jointly funded Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jad.2015.09.00

Continuum modeling of the equilibrium and stability of animal flocks

Groups of animals often tend to arrange themselves in flocks that have characteristic spatial attributes and temporal dynamics. Using a dynamic continuum model for a flock of individuals, we find equilibria of finite spatial extent where the density goes continuously to zero at a well-defined flock edge, and we discuss conditions on the model that allow for such solutions. We also demonstrate conditions under which, as the flock size increases, the interior density in our equilibria tends to an approximately uniform value. Motivated by observations of starling flocks that are relatively thin in a direction transverse to the direction of flight, we investigate the stability of infinite, planar-sheet flock equilibria. We find that long- wavelength perturbations along the sheet are unstable for the class of models that we investigate. This has the conjectured consequence that sheet-like flocks of arbitrarily large transverse extent relative to their thickness do not occur. However, we also show that our model admits approximately sheet-like, 'pancake-shaped', three-dimensional ellipsoidal equilibria with definite aspect ratios (transverse length- scale to flock thickness) determined by anisotropic perceptual/response characteristics of the flocking individuals, and we argue that these pancake-like equilibria are stable to the previously mentioned sheet instability.Comment: 37 pages, 8 figure

Repurposing existing medications for coronavirus disease 2019: protocol for a rapid and living systematic review

BACKGROUND Coronavirus disease 2019 (COVID-19) has no confirmed specific treatments. However, there might be in vitro and early clinical data as well as evidence from severe acute respiratory syndrome and Middle Eastern respiratory syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and 4 groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. TRIAL REGISTRATION PROSPERO 2020 CRD42020175648