Dynamics of Perfectly Wetting Drops under Gravity

We study the dynamics of small droplets of polydimethylsiloxane (PDMS) silicone oil on a vertical, perfectly-wetting, silicon wafer. Interference videomicroscopy allows us to capture the dynamics of these droplets. We use droplets with a volumes typically ranging from 100 to 500 nanolitres (viscosities from 10 to 1000 centistokes) to understand long time derivations from classical solutions. Past researchers used one dimensional theory to understand the typical $t^{1/3}$ scaling for the position of the tip of the droplet in time $t$. We observe this regime in experiment for intermediate times and discover a two-dimensional, similarity solution of the shape of the droplet. However, at long times our droplets start to move more slowly down the plane than the $t^{1/3}$ scaling suggests and we observe deviations in droplet shape from the similarity solution. We match experimental data with simulations to show these deviations are consistent with retarded van der Waals forcing which should become significant at the small heights observed

Consensus mutagenesis reveals that non-helical regions influence thermal stability of horseradish peroxidase

The enzyme horseradish peroxidase has many uses in biotechnology but a stabilized derivative would have even wider applicability. To enhance thermal stability, we applied consensus mutagenesis (used successfully with other proteins) to recombinant horseradish peroxidase and generated five single-site mutants. Unexpectedly, these mutations had greater effects on steady-state kinetics than on thermal stability. Only two mutants (T102A, T110V) marginally exceeded the wild type's thermal stability (4% and 10% gain in half-life at 50 °C respectively); the others (Q106R, Q107D, I180F) were less stable than wild type. Stability of a five-fold combination mutant matched that of Q106R, the least-stable single mutant. These results were perplexing: the Class III plant peroxidases display wide differences in thermal stability, yet the consensus mutations failed to reflect these natural variations. We examined the sequence content of Class III peroxidases to determine if there are identifiable molecular reasons for the stability differences observed. Bioinformatic analysis validated our choice of sites and mutations and generated an archetypal peroxidase sequence for comparison with extant sequences. It seems that both genetic variation and differences in protein stability are confined to non-helical regions due to the presence of a highly conserved alpha-helical structural scaffold in these enzymes

Doppler Signature of a Possible Termination Shock in an Off-Limb Solar Flare

We report striking Doppler velocity gradients observed during the well-observed September 10th 2017 solar flare, and argue that they are consistent with the presence of an above-the-looptop termination shock beneath the flare current sheet. Observations from the Hinode Extreme-ultraviolet Imaging Spectrometer (EIS) measure plasma sheet Doppler shifts up to 35 km/s during the late-phase of the event. By comparing these line-of-sight flows with plane-of-sky measurements, we calculate total velocity downflows of 200+ km/s, orientated 6-10{\deg} out of the plane of sky. The observed velocities drop rapidly at the base of the hot plasma sheet seen in extreme ultraviolet, consistent with simulated velocity profiles predicted by our 2.5D magnetohydrodynamics model that features a termination shock at the same location. Finally, the striking velocity deceleration aligns spatially with the suppression of Fe XXIV non-thermal velocities, and a 35--50 keV hard X-ray looptop source observed by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI). Together, these observations are consistent with the presence of a possible termination shock within the X8.2-class solar flare.Comment: 9 pages, 5 figures; accepted for publication to MNRA

First Observation of Chromospheric Waves in a Sunspot by DKIST/ViSP: The Anatomy of an Umbral Flash

The Visible Spectro-Polarimeter (ViSP) of the NSF Daniel K. Inouye Solar Telescope (DKIST) collected its Science Verification data on May 7-8, 2021. The instrument observed multiple layers of a sunspot atmosphere simultaneously, in passbands of Ca-II 397 nm (H-line), Fe-I 630 nm, and Ca-II 854 nm, scanning the region with a spatial sampling of 0.041" and average temporal cadence of 7.76 seconds, for a 38.8 minute duration. The slit moves southward across the plane-of-the-sky at 3.83 km/s. The spectropolarimetric scans exhibit prominent oscillatory 'ridge' structures which lie nearly perpendicular to the direction of slit motion (north to south). These ridges are visible in maps of line intensity, central wavelength, line width, and both linear and circular polarizations. Contemporaneous Atmospheric Imaging Assembly observations indicate these ridges are purely temporal in character and likely attributed to the familiar chromospheric 3-minute umbral oscillations. We observe in detail a steady umbral flash near the center of the sunspot umbra. Although bad seeing limited the spatial resolution, the unique high signal-to-noise enable us to estimate the shock Mach numbers (= 2), propagation speeds (= 9 km/s), and their impact on longitudinal magnetic field (delta B = 50 G), gas pressure, and temperature (delta T/T = 0.1) of the subshocks over 30 seconds. We also find evidence for rarefaction waves situated between neighboring wave-train shocks. The Ca-II 854 nm line width is steady throughout the umbral flash except for a sharp 1.5 km/s dip immediately before, and comparable spike immediately after, the passage of the shock front. This zig-zag in line width is centered on the subshock and extends over 0.4".Comment: 11 pages, 5 figures, accepted for publication to ApJ Letters (February 2023

Predictors of positive outcomes from ‘Early Intervention in Psychosis’: protocol for a national retrospective cohort study

Background: Psychotic disorders are severe and prevalent mental health conditions associated with long-term disability, reduced quality of life, and substantial economic costs. Early Intervention in Psychosis (EIP) services aim to provide timely and comprehensive treatment for psychotic disorders, and EIP service input is associated with improved outcomes. However, there is limited understanding of the specific components of EIP care that contribute to these improvements. There is significant nationwide variability in the commissioning and delivery of EIP, with individuals receiving different packages of components from different services. In this study, we seek to explore associations between EIP components and clinically significant outcomes, in order to understand the mechanisms underlying improved psychosis care. Methods: This national retrospective cohort study will utilize data from the 2019 National Clinical Audit of Psychosis (NCAP), examining the care received by 10,560 individuals treated by EIP services in England. Exposure data from the NCAP, capturing the components of care delivered by EIP services, will be linked with outcome data from routine NHS Digital datasets over a three-year follow-up period. This will be the first study to use this method to examine this population in England. The primary outcomes will be surrogate measures of relapse of psychosis (hospital admission and referral to community-based crisis intervention services). Secondary outcomes include duration of admissions, emergency hospital attendances, episodes of detention under the Mental Health Act, and all-cause mortality. We will use multilevel regression to examine associations between exposures and outcome events. We will handle missing data using appropriate imputation techniques. Discussion: This study aims to provide valuable insights into the long-term effects of variations in EIP service delivery. The study involves a large, diverse cohort including individuals treated by every EIP service in England. While there are limitations inherent in the observational nature of the study, any associations identified will be of great relevance to clinicians, researchers, and policymakers seeking to optimize EIP care. The results will enable more targeted treatment planning, resource allocation, and potential innovations in EIP care, ultimately leading to improved prognoses for people experiencing psychosis

Effects of mutations in the helix G region of horseradish peroxidase

Horseradish peroxidase (HRP) has long attracted intense research interest and is used in many biotechnological fields, including diagnostics, biosensors and biocatalysis. Enhancement of HRP catalytic activity and/or stability would further increase its usefulness. Based on prior art, we substituted solvent-exposed lysine and glutamic acid residues near the proximal helix G (Lys 232, 241; Glu 238, 239) and between helices F and F′ (Lys 174). Three single mutants (K232N, K232F, K241N) demonstrated increased stabilities against heat (up to 2-fold) and solvents (up to 4-fold). Stability gains are likely due to improved hydrogen bonding and space-fill characteristics introduced by the relevant substitution. Two double mutants showed stability gains but most double mutations were non-additive and non-synergistic. Substitutions of Lys 174 or Glu 238 were destabilising. Unexpectedly, notable alterations in steady-state Vm/E values occurred with reducing substrate ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)), despite the distance of the mutated positions from the active site

Predictors of positive outcomes from ‘Early Intervention in Psychosis’: protocol for a national retrospective cohort study

BackgroundPsychotic disorders are severe and prevalent mental health conditions associated with long-term disability, reduced quality of life, and substantial economic costs. Early Intervention in Psychosis (EIP) services aim to provide timely and comprehensive treatment for psychotic disorders, and EIP service input is associated with improved outcomes. However, there is limited understanding of the specific components of EIP care that contribute to these improvements. There is significant nationwide variability in the commissioning and delivery of EIP, with individuals receiving different packages of components from different services. In this study, we seek to explore associations between EIP components and clinically significant outcomes, in order to understand the mechanisms underlying improved psychosis care.MethodsThis national retrospective cohort study will utilize data from the 2019 National Clinical Audit of Psychosis (NCAP), examining the care received by 10,560 individuals treated by EIP services in England. Exposure data from the NCAP, capturing the components of care delivered by EIP services, will be linked with outcome data from routine NHS Digital datasets over a three-year follow-up period. This will be the first study to use this method to examine this population in England. The primary outcomes will be surrogate measures of relapse of psychosis (hospital admission and referral to community-based crisis intervention services). Secondary outcomes include duration of admissions, emergency hospital attendances, episodes of detention under the Mental Health Act, and all-cause mortality. We will use multilevel regression to examine associations between exposures and outcome events. We will handle missing data using appropriate imputation techniques.DiscussionThis study aims to provide valuable insights into the long-term effects of variations in EIP service delivery. The study involves a large, diverse cohort including individuals treated by every EIP service in England. While there are limitations inherent in the observational nature of the study, any associations identified will be of great relevance to clinicians, researchers, and policymakers seeking to optimize EIP care. The results will enable more targeted treatment planning, resource allocation, and potential innovations in EIP care, ultimately leading to improved prognoses for people experiencing psychosis

Selective disruption of Tcf7l2 in the pancreatic β cell impairs secretory function and lowers β cell mass

Type 2 diabetes (T2D) is characterized by β cell dysfunction and loss. Single nucleotide polymorphisms in the T-cell factor 7-like 2 (TCF7L2) gene, associated with T2D by genome-wide association studies, lead to impaired β cell function. While deletion of the homologous murine Tcf7l2 gene throughout the developing pancreas leads to impaired glucose tolerance, deletion in the β cell in adult mice reportedly has more modest effects. To inactivate Tcf7l2 highly selectively in β cells from the earliest expression of the Ins1 gene (∼E11.5) we have therefore used a Cre recombinase introduced at the Ins1 locus. Tcfl2fl/fl::Ins1Cre mice display impaired oral and intraperitoneal glucose tolerance by 8 and 16 weeks, respectively, and defective responses to the GLP-1 analogue liraglutide at 8 weeks. Tcfl2fl/fl::Ins1Cre islets displayed defective glucose- and GLP-1-stimulated insulin secretion and the expression of both the Ins2 (∼20%) and Glp1r (∼40%) genes were significantly reduced. Glucose- and GLP-1-induced intracellular free Ca2+ increases, and connectivity between individual β cells, were both lowered by Tcf7l2 deletion in islets from mice maintained on a high (60%) fat diet. Finally, analysis by optical projection tomography revealed ∼30% decrease in β cell mass in pancreata from Tcfl2fl/fl::Ins1Cre mice. These data demonstrate that Tcf7l2 plays a cell autonomous role in the control of β cell function and mass, serving as an important regulator of gene expression and islet cell coordination. The possible relevance of these findings for the action of TCF7L2 polymorphisms associated with Type 2 diabetes in man is discusse

Relationship between psychological and biological factors and physical activity and exercise behaviour in Filipino students

The aim of the present study was threefold. Firstly, it investigated whether a general measure or specific measure of motivational orientation was better in describing the relationship between motivation and exercise behaviour. Secondly, it examined the relationship between the four most popular indirect methods of body composition assessment and physical activity and exercise patterns. Thirdly, the interaction between motivation and body composition on physical activity and exercise behaviour was explored in a sample of 275 Filipino male and female students. Males were found to have higher levels of exercise whereas females had higher levels of physical activity. Furthermore, general self-motivation together with body weight and percentage body fat were found to be the best predictor of exercise behaviour whereas the tension/pressure subscale of the ‘Intrinsic Motivation Inventory’ (IMI) was the best predictor of levels of physical activity. However, significant gender differences were observed. That is, for the males only self-motivation and for the females only body weight and BMI predicted exercise behaviour. Also, tension/pressure predicted physical activity levels for the females but not the males. No inverse relationship was found between the four body composition measures and exercise and physical activity behaviour. The results support the notion that the psychobiological approach might be particularly relevant for high intensity exercise situations but also highlights some important gender differences. Finally, the results of this study emphasise the need for more cross-cultural research