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Through their role in buttressing upstream ice flow, Antarctic ice shelves play an important part in regulating future sea-level change. Reduction in ice-shelf buttressing caused by increased ocean-induced melt along their undersides is now understood to be one of the key drivers of ice loss from the Antarctic ice sheet. However, despite the importance of this forcing mechanism, most ice-sheet simulations currently rely on simple melt parameterisations of this ocean-driven process since a fully coupled ice–ocean modelling framework is prohibitively computationally expensive. Here, we provide an alternative approach that is able to capture the greatly improved physical description of this process provided by large-scale ocean-circulation models over currently employed melt parameterisations but with trivial computational expense. This new method brings together deep learning and physical modelling to develop a deep neural network framework, MELTNET, that can emulate ocean model predictions of sub-ice-shelf melt rates. We train MELTNET on synthetic geometries, using the NEMO ocean model as a ground truth in lieu of observations to provide melt rates both for training and for evaluation of the performance of the trained network. We show that MELTNET can accurately predict melt rates for a wide range of complex synthetic geometries, with a normalised root mean squared error of 0.11 m yr−1 compared to the ocean model. MELTNET calculates melt rates several orders of magnitude faster than the ocean model and outperforms more traditional parameterisations for > 96 % of geometries tested. Furthermore, we find MELTNET's melt rate estimates show sensitivity to established physical relationships such as changes in thermal forcing and ice-shelf slope. This study demonstrates the potential for a deep learning framework to calculate melt rates with almost no computational expense, which could in the future be used in conjunction with an ice sheet model to provide predictions for large-scale ice sheet models.

Imonitea freshwater stream serves as a major source of water for domestic and agricultural applications for the inhabitants of Imonitea, in Ndoni of Ogba-Egbema Local Government Area of Rivers State, Nigeria. This research was conducted to investigate the physicochemical characteristics and microbial loads of the flood and post-flood water quality of the Imonitea fresh water stream using standard methods. Water samples were collected at both flood and post flood periods using standard methods. The properties of the freshwater at both flood and post flood periods were respectively: pH (6.41+0.15; 6.88+0.15); total dissolved solids (88.87+ 20.07 mg/l; 103.13 +16.76 mg/l), total hydrocarbon (4.20+0.77 mg/l; 4.94+0.86 mg/l), electrical conductivity(126.6+17.59 µS/cm; 140.53+33.99 µS/cm), nitrate(0.11+0.08 mg/l; 1.26;+1.45 mg/l), turbidity(51.88+7.67 NTU; 20.39+16.76 NTU), sulphate(3.52+1.25 mg/l; 2.44+0.41mg/l). The levels of heavy metals were: iron (1.20+0.50 mg/l; 110.98+9.94 mg/l), lead (0.30+0.20mg/l; 1.25+0.51 mg/l), cadmium (0.12+0.01 mg/l; 0.07+0.03 mg/l). On the other hand microbiological loads at flood and post flood periods were 1.84±0.92 cfu/ml; 3.56 ± 1.36 cfu/ml and 1.72 +1.92 cfu/ml; 3.56 +.1.20 cfu/ml respectively. At both periods, turbidity and total dissolved solids exceeded national standards. Although lead levels were within permissible limits, iron and chromium exceeded their permissible limits. The microbiological loads at both periods also exceeded national limits. The Water Quality Index was very high (3,192.81; 3,838.13), implying that the freshwater body was not fit for human consumption.

Background Fatigue failure criteria for fibre reinforced polymer composites used in the design of marine structures are based on the micromechanical behaviour (e.g. stiffness properties) of their constituents. In the literature, there is a lack of information regarding the stiffness degradation of fibres, polymer matrix and fibre/matrix interface regions affected by environmental fatigue. Objective The aim of present study is to characterize the stiffness properties of composite constituents using the nanoindentation technique when fatigue failure of composites is due to the combined effect of sea water exposure and cyclic mechanical loads. Methods In the present study, the nanoindentation technique was used to characterize the stiffness properties of composite constituents where the effects of neighbouring phases, material pile up and viscoplasticity properties of the polymer matrix are corrected by finite element simulation. Results The use of finite element simulation in conjunction with nanoindentation test data, results in more accurate estimation of projected indented area which is required for measuring the properties of composite constituents. In addition, finite element simulation provides a greater understanding of the stress transfer between composite constituents during the nanoindentation process. Conclusions Results of nanoindentation testing on the composite microstructure of environmentally fatigue failed composite test coupons establish a strong link to the stiffness degradation of the fiber/matrix interface regions, verifying the degradation of composite constituents identified by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) analysis.

Background Long Covid is associated with multiple symptoms and impairment in multiple organs [1]. Cardiac impairment has been reported to varying degrees by varying methodologies in cross-sectional studies. Using cardiovascular magnetic resonance (CMR), we investigated the 12-month trajectory of cardiac impairment in individuals with Long Covid. Purpose We conducted a prospective, longitudinal, 1-year study in individuals with Long Covid to investigate 1) the characteristics and trajectory of cardiac impairment; 2) the impact of acute hospitalisation for COVID-19 on cardiac impairment; and 3) pathways for designing and improving clinical management for individuals at risk of cardiac impairment. Methods 534 individuals with Long Covid underwent baseline CMR (quantitative T1 and T2 mapping, cardiac mass, volumes, function, and strain) and multi-organ MRI at 6 months (IQR 4.3,7.3) since first post-COVID-19 symptoms. If abnormal findings were reported at baseline, individuals were rescanned at 12.6 months (IQR 11.4, 14.2) (n=330). Symptoms, standardised questionnaires, and blood samples were collected at both timepoints (Figure 1). Cardiac impairment was defined as one or more of: low left or right ventricular ejection fraction (LVEF and RVEF), high left or right ventricular end diastolic volume (LVEDV and RVEDV), impaired left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac independent AHA segments. A significant change over time was reported by comparison with 92 healthy controls. Results The technical success of this multiorgan assessment in a non-acute setting was 99.1% at baseline, and 98.3% at follow-up, with 99.6% and 98.8% for CMR, respectively. Of individuals with Long Covid, 19% had cardiac impairment at baseline; 70% had complete paired data at 12 months. Of those with paired data, 58% presented with ongoing cardiac impairment at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms, or clinical outcomes. At baseline, low LVEF, high RVEDV and reduced GLS were associated with cardiac impairment; however, while elevated T1 was associated with less symptom severity at 12 months, individuals with low LVEF at baseline were associated with ongoing cardiac impairment 1 year post-infection (Figure 2). Conclusion Cardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Radical (EU) and Innovative UK (UK national) (and others)

The cytotoxicity against five human tumor cell lines (THP-1, U937, Molt-4, Colo-205 and NCI-H460) of three water soluble copper(II) coordination compounds containing the ligands 3,3′-(ethane-1,2-diylbis(azanediyl))dipropanamide (BCEN), 3,3′-(piperazine-1,4-diyl)dipropanamide (BPAP) or 3,3′-and (1,4-diazepane-1,4-diyl)dipropanamide (BPAH) are reported in this work. The ligands contain different diamine units (ethylenediamine, piperazine or homopiperazine) and two propanamide units attached to the diamine centers, resulting in N2O2 donor sets. The complex containing homopiperazine unit presented the best antiproliferative effect and selectivity against lung cancer cell line NCI-H460, showing inhibitory concentration (IC50) of 58 μmol dm−3 and Selectivity Index (SI) > 3.4. The mechanism of cell death promoted by the complex was investigated by Sub-G1 cell population analysis and annexin V and propidium iodide (PI) labeling techniques, suggesting that the complex promotes death by apoptosis. Transmission electron microscopy investigations are in agreement with the results presented by mitochondrial membrane potential analysis and also show the impairment of other organelles, including endoplasmic reticulum.

Background There are no effective treatments for diffuse intrinsic pontine glioma (DIPG); median survival is 11.2 months. Bevacizumab has the potential to improve quality of life (QOL) and survival in DIPG but has never been evaluated systematically. The aim of this review was to assess Bevacizumab’s role in the treatment of DIPG. Methods MEDLINE, EMBASE, Scopus, and Web of Science were searched for relevant studies using terms developed from alternatives for Bevacizumab and DIPG. One reviewer screened titles and abstracts, then two reviewers screened full texts. Data were extracted into tables and quality assessed using methodological index for non-randomized studies and JBI tools. Results Searching revealed 1001 papers; after deduplication 851 remained. After screening of titles and abstracts, then 28 full texts, 11 studies were included. Four studies reported a median overall survival longer than historical data, however, two found no significant impact of Bevacizumab. Five studies reported a radiological response in a proportion of participants and two reported no response. Three studies, evaluating clinical response, reported improvement in a proportion of patients. Three studies, evaluating QOL, reported stability or improvement. Four studies, evaluating steroid use, reported reductions in the proportion of patients receiving steroids. In radiation necrosis treatment, Bevacizumab led to clinical improvement in 6/12 patients in 2 studies and permitted a reduction in steroid use in most patients. Conclusions Insufficient evidence means the role of Bevacizumab in the treatment of DIPG is unclear. However, Bevacizumab may be beneficial to some patients. The review highlights the need for further research in this area.

Epithelial tissues provide an important barrier function in animals, but these tissues are subjected to extreme strains during day-to-day activities such as feeding and locomotion. Understanding tissue mechanics and the adaptive response in dynamic force landscapes remains an important area of research. Here we carry out a multi-modal study of a simple yet highly dynamic organism, Trichoplax adhaerens, and report the discovery of abrupt, bulk epithelial tissue fractures induced by the organism’s own motility. Coupled with rapid healing, this discovery accounts for dramatic shape change and physiological asexual division in this early-divergent metazoan. We generalize our understanding of this phenomenon by codifying it in a heuristic model focusing on the debonding–bonding criterion in a soft, active living material. Using a suite of quantitative experimental and numerical techniques, we demonstrate a force-driven ductile-to-brittle material transition governing the morphodynamics of tissues pushed to the edge of rupture. Characterizing the epithelial tissue of a shape-shifting marine animal as an integrated composite material reveals a ductile-to-brittle phase transition that captures how the tissue responds to failure.

The reaction between differently substituted borasiloxanes and 2,5-bis(3-pyridylethynyl)thiophene provided the first example of luminescent borasiloxane-based chiral helices held together by N-B bonds. The starting building blocks and the helices were fully characterized, and the nature of the N-B bond rationalized by means of theoretical calculations.

Early in the coronavirus disease 2019 (COVID-19) pandemic, global governing bodies prioritized transmissibility-based precautions and hospital capacity as the foundation for delay of elective procedures. As elective surgical volumes increased, convalescent COVID-19 patients faced increased postoperative morbidity and mortality and clinicians had limited evidence for stratifying individual risk in this population. Clear evidence now demonstrates that those recovering from COVID-19 have increased postoperative morbidity and mortality. These data—in conjunction with the recent American Society of Anesthesiologists guidelines—offer the evidence necessary to expand the early pandemic guidelines and guide the surgeon’s preoperative risk assessment. Here, we argue elective surgeries should still be delayed on a personalized basis to maximize postoperative outcomes. We outline a framework for stratifying the individual COVID-19 patient’s fitness for surgery based on the symptoms and severity of acute or convalescent COVID-19 illness, coagulopathy assessment, and acuity of the surgical procedure. Although the most common manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19 pneumonitis, every system in the body is potentially afflicted by an endotheliitis. This endothelial derangement most often manifests as a hypercoagulable state on admission with associated occult and symptomatic venous and arterial thromboembolisms. The delicate balance between hyper and hypocoagulable states is defined by the local immune-thrombotic crosstalk that results commonly in a hemostatic derangement known as fibrinolytic shutdown. In tandem, the hemostatic derangements that occur during acute COVID-19 infection affect not only the timing of surgical procedures, but also the incidence of postoperative hemostatic complications related to COVID-19-associated coagulopathy (CAC). Traditional methods of thromboprophylaxis and treatment of thromboses after surgery require a tailored approach guided by an understanding of the pathophysiologic underpinnings of the COVID-19 patient. Likewise, a prolonged period of risk for developing hemostatic complications following hospitalization due to COVID-19 has resulted in guidelines from differing societies that recommend varying periods of delay following SARS-CoV-2 infection. In conclusion, we propose the perioperative, personalized assessment of COVID-19 patients’ CAC using viscoelastic hemostatic assays and fluorescent microclot analysis.

Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in Covid Associated Coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill Covid-19 patients with associated elevation of D-dimer. Elevated d-dimer confirms that coagulation, followed by fibrinolysis, has occurred. These findings imply that, during CAC, three enzymes—thrombin, Factor XIIIa and plasmin—must have acted in sequence. However, limitations in standard VET analyses preclude exploration of the earliest phases of clot induction, as well as clot formation and clot dissolution in flowing blood. Herein we describe a novel method illuminating aspects of this unexplored area. In addition, we created an ex vivo blood flow model in which the interactions of thrombin, Factor XIII and plasmin with fibrinogen can be studied, allowing determination of Soluble Fibrin (SF), the highly unstable form of fibrin that precedes the appearance of a visible clot. This model allows determination of the SF level at which fibrin microclots begin to form and the length of time the resulting microclots persist under normal fibrinolytic attack. In addition, the flow model allows exploration of the late fibrinolytic shutdown that VET has previously demonstrated in CAC through standard methodology.

Through their role in buttressing upstream ice flow, Antarctic ice shelves play an important part in regulating future sea level change. Reduction in ice-shelf buttressing caused by increased ocean-induced melt along their undersides is now understood to be one of the key drivers of ice loss from the Antarctic Ice Sheet. However, despite the importance of this forcing mechanism most ice-sheet simulations currently rely on simple melt-parametrisations of this ocean-driven process, since a fully coupled ice-ocean modelling framework is prohibitively computationally expensive. Here, we provide an alternative approach that is able to capture the greatly improved physical description of this process provided by large-scale ocean-circulation models over currently employed melt-parameterisations but with trivial computational expense. We introduce a new approach that brings together deep learning and physical modelling to develop a deep neural network framework, MELTNET, that can emulate ocean model predictions of sub-ice shelf melt rates. We train MELTNET on synthetic geometries, using the NEMO ocean model as a ground-truth in lieu of observations to provide melt rates both for training and to evaluate the performance of the trained network. We show that MELTNET can accurately predict melt rates for a wide range of complex synthetic geometries and outperforms more traditional parameterisations for > 95 % of geometries tested. Furthermore, we find MELTNET's melt rate estimates show sensitivity to established physical relationships such as a changes in thermal forcing and ice shelf slope. This study demonstrates the potential for a deep learning framework to calculate melt rates with almost no computational expense, that could in the future be used in conjunction with an ice sheet model to provide predictions for large-scale ice sheet models.

Offshore platforms, subsea pipelines, wells and related fixed structures supporting the oil and gas (O&G) industry are prevalent in oceans across the globe, with many approaching the end of their operational life and requiring decommissioning. Although structures can possess high ecological diversity and productivity, information on how they interact with broader ecological processes remains unclear. Here, we review the current state of knowledge on the role of O&G infrastructure in maintaining, altering or enhancing ecological connectivity with natural marine habitats. There is a paucity of studies on the subject with only 33 papers specifically targeting connectivity and O&G structures, although other studies provide important related information. Evidence for O&G structures facilitating vertical and horizontal seascape connectivity exists for larvae and mobile adult invertebrates, fish and megafauna; including threatened and commercially important species. The degree to which these structures represent a beneficial or detrimental net impact remains unclear, is complex and ultimately needs more research to determine the extent to which natural connectivity networks are conserved, enhanced or disrupted. We discuss the potential impacts of different decommissioning approaches on seascape connectivity and identify, through expert elicitation, critical knowledge gaps that, if addressed, may further inform decision making for the life cycle of O&G infrastructure, with relevance for other industries (e.g. renewables). The most highly ranked critical knowledge gap was a need to understand how O&G structures modify and influence the movement patterns of mobile species and dispersal stages of sessile marine species. Understanding how different decommissioning options affect species survival and movement was also highly ranked, as was understanding the extent to which O&G structures contribute to extending species distributions by providing rest stops, foraging habitat, and stepping stones. These questions could be addressed with further dedicated studies of animal movement in relation to structures using telemetry, molecular techniques and movement models. Our review and these priority questions provide a roadmap for advancing research needed to support evidence-based decision making for decommissioning O&G infrastructure.

Objective Our goal is to establish the feasibility of using an artificially intelligent chatbot in diverse healthcare settings to promote COVID-19 vaccination. Methods We designed an artificially intelligent chatbot deployed via short message services and web-based platforms. Guided by communication theories, we developed persuasive messages to respond to users’ COVID-19-related questions and encourage vaccination. We implemented the system in healthcare settings in the U.S. between April 2021 and March 2022 and logged the number of users, topics discussed, and information on system accuracy in matching responses to user intents. We regularly reviewed queries and reclassified responses to better match responses to query intents as COVID-19 events evolved. Results A total of 2479 users engaged with the system, exchanging 3994 COVID-19 relevant messages. The most popular queries to the system were about boosters and where to get a vaccine. The system's accuracy rate in matching responses to user queries ranged from 54% to 91.1%. Accuracy lagged when new information related to COVID emerged, such as that related to the Delta variant. Accuracy increased when we added new content to the system. Conclusions It is feasible and potentially valuable to create chatbot systems using AI to facilitate access to current, accurate, complete, and persuasive information on infectious diseases. Such a system can be adapted to use with patients and populations needing detailed information and motivation to act in support of their health.

Determinants of survivorship outcomes are emerging from limited studies of medulloblastoma (MB) survivors. We undertook an integrated analysis of biological (tumour group, host genetics) and clinico-demographic features in patients treated on the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 clinical trials with available quality of survival (QoS) data (n=218), to determine key correlates of survivorship, and their clinical potential. Treatment/demographic factors and molecular subgroup (MBWNT, MBSHH, MBGrp3, MBGrp4) were assessed against health status, behavioural functioning, and health-related quality of life (HrQoL). In DNA from HIT-SIOP-PNET4 (n=74), 39 candidate SNPs with known modifying effects on neurocognitive outcomes (e.g., involved in oxidative stress/inflammation) were genotyped and assessed against Wechsler Intelligence Scale (WISC) scores. As expected, MBSHH was associated with improved HrQoL, but subgroup did not associate further with QoS outcomes. SIOP-UKCCSG-PNET3 patients receiving chemotherapy before craniospinal irradiation (CSI) had significantly lower health status (p=0.021) and behavioural functioning (p

The importance of resolving mesoscale air-sea interactions to represent cyclones impacting the East Coast of Australia, the so-called East Coast Lows (ECLs), is investigated using the Australian Regional Coupled Model based on NEMO-OASIS-WRF (NOW) at urn:x-wiley:2169897X:media:jgrd57355:jgrd57355-math-0001 resolution. The fully coupled model is shown to be capable of reproducing correctly relevant features such as the seasonality, spatial distribution and intensity of ECLs while it partially resolves mesoscale processes, such as air-sea feedbacks over ocean eddies and fronts. The mesoscale thermal feedback (TFB) and the current feedback (CFB) are shown to influence the intensity of northern ECLs (north of urn:x-wiley:2169897X:media:jgrd57355:jgrd57355-math-0002), with the TFB modulating the pre-storm sea surface temperature by shifting ECL locations eastwards and the CFB modulating the wind stress. By fully uncoupling the atmospheric model of NOW, the intensity of northern ECLs is increased due to the absence of the cold wake that provides a negative feedback to the cyclone. The number of ECLs might also be affected by the air-sea feedbacks but large interannual variability hampers significant results with short term simulations. The TFB and CFB modify the climatology of sea surface temperature (mean and variability) but no direct link is found between these changes and those noticed in ECL properties. These results show that the representation of ECLs, mainly north of urn:x-wiley:2169897X:media:jgrd57355:jgrd57355-math-0003, depend on how air-sea feedbacks are simulated. This is particularly important for atmospheric downscaling of climate projections as small-scale sea surface temperature interactions and the effects of ocean currents are not accounted for.

Confluent epithelial tissues can be viewed as soft active solids, as their individual cells contract in response to local conditions. Little is known about the emergent properties of such materials. Empirical observations have shown contraction waves propagation in various epithelia, yet the governing mechanism, as well as its physiological function, is still unclear. Here we propose an experiment-inspired model for such dynamic epithelia. We show how the widespread cellular response of contraction-under-tension is sufficient to give rise to propagating contraction pulses, by mapping numerically and theoretically the consequences of such a cellular response. The model explains observed phenomena but also predicts enhanced rip-resistance as an emergent property of such cellular sheets. Unlike healing post-rupture, these sheets avoid it by actively re-distributing external stresses across their surface. The mechanism is relevant to a broad class of tissues, especially such under challenging mechanical conditions, and may inspire engineering of synthetic materials. Observations on confluent epithelial tissues show the emergence of dynamic contraction patterns that are suspected to be governed mechanically. Here, the authors propose a model for epithelial sheets and show that cells’ Extension-Induced-Contraction response explains experimentally-observed contraction pulses, that along with a cell softening response enhances epithelial resistance to rupture.

Cilia and flagella are fundamental units of motion in cellular biology. These beating, hair-like organelles share a common basic structure but maintain widely varying functions in systems ranging from the isolated flagella of swimming algae to the dense ciliary carpets that pump fluid in the brains of mammals. Experiments and models have begun to elucidate the inner workings of single cilia as complex nonlinear oscillators, and the variety of hydrodynamical phenomena that result from beating dynamics. These results have shed light on complex locomotion strategies observed in single-celled microorganisms and collective phenomena observed in microbial suspensions. In animal systems, dense ciliary arrays exhibit a variety of emergent phenomena, including active filtration, noise robustness and metachronal waves. Surprising phenomena have been observed in neuronally controlled ciliary arrays, demonstrating the need for new physical models of cilia that include central control, defect dynamics and topology. We review the emergent physics of cilia across scales, starting from the microscale dynamics of single cilia, and then proceeding to microorganisms and animal systems. Cilia are hair-like organelles that enable cellular locomotion. This Review considers cilia from a dynamical systems perspective, discussing the nonlinear oscillations seen in the single cilia of microorganisms and the emergent topological phenomena seen in the ciliary arrays of animals.

Introduction A neutrophilic infiltrate characterizes bacterial pneumonia. Macrophage infiltration is similarly characteristic of the viral pneumonia caused by SARS‐CoV‐2. These infiltrating macrophages, while phagocytic and capable of engulfing virus laden alveolar cells, are also rich in tissue factor—a thromboplastin. This prothrombotic aspect likely explains how a respiratory virus whose malign effects should be confined to the oropharynx, bronchi and lungs, can cause a panoply of extra‐pulmonary organ disorders. Elevated ferritin levels in ICU Covid 19 patients, and elevated acute phase proteins suggest immune overreaction. Elevated d‐dimers implicate clotting as well. This evidence links hyperactive innate immunity (macrophage lung infiltrates) with the elevated levels of oligomeric fibrin present in the bloodstream of these patients. Methods An in‐house assay measuring oligomeric (soluble) fibrin (also referred to as soluble fibrin monomer complexes or SFMC) in whole blood, previously developed for monitoring incipient disseminated intravascular coagulation (DIC) during liver transplantation, was made available to COVID ICU attendings. Since SFMC constitutes the input to intravascular fibrin clots and d‐dimer reflects fibrin clot dissolution, it was thought that the two tests, run in tandem along with assays of immune activation, might clarify the frequency and possibly the cause of DIC in patients with severe COVID‐19 pneumonia. Results Classical DIC with intravascular clotting and thrombocytopenia was documented only rarely. However, early in the pandemic shortly after the assay was made available, it identified three patients undergoing acute defibrination. In each patient virtually all of the body's fibrinogen was transformed into SFMC over 3–4 days and deposited somewhere in the vasculature without any gross clots being detected. Conclusions Three COVID‐19 patients with evidence of a hyperactive immune response (elevated ferritin and acute phase proteins) defibrinated while blood levels of SFMC were being monitored. SFMC levels that were five times higher than normal appeared in the circulation during the defibrination process. SFMC at these levels may precipitate as showers of microclots, damaging heart, kidney, brain, and so forth.

Large uncertainties in Antarctic sea level projections are related to ocean-driven melting (Seroussi et al., 2020; Jourdain et al., 2020; Reese et al., 2020; Edwards et al., in press) and the marine ice sheet instability (Robel et al., 2019). ‘Hindcasting’ simulations that follow the trajectory of the Antarctic Ice Sheet from pre-industrial conditions to present-day, are a useful tool to better constrain such uncertainties. We here perform historic simulations with the Parallel Ice Sheet Model. The simulations are forced by changes in the ocean and atmosphere from GCM output of CMIP5 as selected for ISMIP6 (Barthel et al., 2020). Sub-shelf melting is modeled using PICO (Olbers & Hellmer, 2010; Reese et al., 2018), with careful consideration of PICO’s parameters: the parameters for heat exchange across the ice ocean interface as well as the overturning strength are fitted with estimates of the melt sensitivity based on observations (Jenkins et al., 2018). Present-day observation of sub-shelf melting and mass loss inform parameter selection using an ensemble approach (Albrecht et al., 2020; Reese et al., 2020). The historic simulations provide an important basis to assess the future evolution and stability of Antarctic grounding lines. This work is done in the framework of the H2020 TiPACCs project.

The Marine Ice Sheet-Ocean Model Intercomparison Project (MISOMIP) is a community effort sponsored by the Climate and Cryosphere (CliC) project. MISOMIP aims to design and coordinate a series of MIPs—some idealized and realistic—for model evaluation, verification with observations, and future projections for key regions of the West Antarctic Ice Sheet (WAIS). The first phase of the project, MISOMIP1, was an idealized, coupled set of experiments that combined elements from the MISMIP+ and ISOMIP+ standalone experiments for ice-sheet and ocean models, respectively. These MIPs had 3 main goals: 1) to provide simplified experiments that allow model developers to compare their results with those from other models; 2) to suggest a path for testing components in the process of developing a coupled ice sheet-ocean model; and 3) to enable a large variety of parameter and process studies that branch off from these basic experiments.Here, we describe preliminary analysis of the MISOMIP1 results. Eight models in 14 configurations participated in the MIP. In keeping with analysis of the MISMIP+ experiment, we find that the choice of basal friction parameterizations in the ice-sheet component (Weertman vs. Coulomb limited) has a particularly significant impact on the rate of ice-sheet retreat but the choice of stress approximation (SSA, SSA* or L1Lx) seems to have little impact. Models with Coulomb-limited basal friction also tend to be those with the highest melt rates, confirming a positive feedback between melt and retreat in the MISOMIP1 configuration seen in previous work. The ocean component’s treatment of the boundary layer below the ice shelf also has a significant impact on melt rates and resulting retreat, consistent with findings based on ISOMIP+. Feedbacks between the components lead to localized features in the melt rates and the ice geometry not seen in standalone simulations, though the ~2-km horizontal and ~20-m vertical resolution of these simulations appears to be too coarse to produce long-lived, sub-ice-shelf channels seen at higher resolution.

Coconut oil from coconut kernel is a source of natural cooking oil for most people in tropical countries. This study was undertaken to evaluate the effects of coconut oil on some biochemical, haematological and histological parameters in albino rats. Two phases of experiment with four groups of male albino rats each consisting of five rats weighing about 180 – 200 g were used for this study. Phase 1 of the experiment involves feeding of albino rats with commercial rodent chow mixed with coconut oil, coconut oil supplemented diet (COSD) while phase 2 experimental rats were treated with coconut oil orally. Group 1 served as the control for both phases of treatment, groups 2, 3 and 4 were treated with 3 ml/kg, 6 ml/kg and 12 ml/kg of COSD and coconut oil respectively for 4 weeks. Result of both phases of experiment showed significant increase (p≤0.05) in serum concentrations of AST, ALP and ALT levels. Also, the result showed that the levels of urea and creatinine decreased significantly when compared with the control group. Haematological results showed that levels of haemoglobin and PCV for both phases of treatment decreased significantly (p≤0.05) compared with the control group. Total protein for COSD treatment phase showed a significant increase while total protein for coconut oil (CO) oral administration treatment phase decreased significantly for only group 4 albino rats when compared with control. Histopathological results showed normal liver hepatocytes in the treated albino rats except for some albino rats with microvesicular steatosis. This study has also shown that coconut oil within the dosage administered cause mild inflammation of the liver in some of the albino rats.

The goal of most studies published on sand contaminants is to gather and discuss knowledge to avoid faecal contamination of water by run-offs and tide-retractions. Other life forms in the sand, however, are seldom studied but always pointed out as relevant. The Mycosands initiative was created to generate data on fungi in beach sands and waters, of both coastal and freshwater inland bathing sites. A team of medical mycologists and water quality specialists explored the sand culturable mycobiota of 91 bathing sites, and water of 67 of these, spanning from the Atlantic to the Eastern Mediterranean coasts, including the Italian lakes and the Adriatic, Baltic, and Black Seas. Sydney (Australia) was also included in the study. Thirteen countries took part in the initiative. The present study considered several fungal parameters (all fungi, several species of the genus Aspergillus and Candida and the genera themselves, plus other yeasts, allergenic fungi, dematiaceous fungi and dermatophytes). The study considered four variables that the team expected would influence the results of the analytical parameters, such as coast or inland location, urban and non-urban sites, period of the year, geographical proximity and type of sediment. The genera most frequently found were Aspergillus spp., Candida spp., Fusarium spp. and Cryptococcus spp. both in sand and in water. A site-blind median was found to be 89 Colony-Forming Units (CFU) of fungi per gram of sand in coastal and inland freshwaters, with variability between 0 and 6400 CFU/g. For freshwater sites, that number was 201.7 CFU/g (0, 6400 CFU/g (p = 0.01)) and for coastal sites was 76.7 CFU/g (0, 3497.5 CFU/g). For coastal waters and all waters, the median was 0 CFU/ml (0, 1592 CFU/ml) and for freshwaters 6.7 (0, 310.0) CFU/ml (p < 0.001). The results advocate that beaches should be monitored for fungi for safer use and better management. © 2021 Elsevier B.V.

International audience; Like many western boundary currents, the East Australian Current (EAC) extension is projected to get stronger and warmer in the future. The CMIP5 multimodel mean (MMM) projection suggests up to 5°C of warming under an RCP85 scenario by 2100. Previous studies employed Sverdrup balance to associate a trend in basin wide zonally integrated wind stress curl (resulting from the multidecadal poleward intensification in the westerly winds over the Southern Ocean) with enhanced transport in the EAC extension. Possible regional drivers are yet to be considered. Here we introduce the NEMO-OASIS-WRF coupled regional climate model as a framework to improve our understanding of CMIP5 projections. We analyze a hierarchy of simulations in which the regional atmosphere and ocean circulations are allowed to freely evolve subject to boundary conditions that represent present-day and CMIP5 RCP8.5 climate change anomalies. Evaluation of the historical simulation shows an EAC extension that is stronger than similar ocean-only models and observations. This bias is not explained by a linear response to differences in wind stress. The climate change simulations show that regional atmospheric CMIP5 MMM anomalies drive 73% of the projected 12 Sv increase in EAC extension transport whereas the remote ocean boundary conditions and regional radiative forcing (greenhouse gases within the domain) play a smaller role. The importance of regional changes in wind stress curl in driving the enhanced EAC extension is consistent with linear theory where the NEMO-OASIS-WRF response is closer to linear transport estimates compared to the CMIP5 MMM. Plain Language Summary In recent decades, enhanced warming, severe marine heatwaves, and increased transport by the East Australian Current have led to the invasion of nonnative species and the destruction of kelp forests east of Tasmania. The East Australian Current extension is projected to get stronger and warmer in the future. We seek to better understand coupled climate model projections for the Tasman Sea. This is difficult because there is large model diversity and considerable uncertainty as to how and where future changes will occur. In addition, little is known about the possible importance of regional versus large-scale changes in surface time-mean winds in driving future circulation changes. Here we use a single limited-domain ocean-atmosphere coupled model that takes the average model projections as its inputs and finds that changes in the regional wind stress are most important for the enhanced projected East Australian Current extension. We also find that these projected changes are consistent with simple linear theory and the simulated regional changes in wind stress.

Epithelial tissues in many contexts can be viewed as soft active solids. Their active nature is manifested in the ability of individual cells within the tissue to contract and/or remodel their mechanical properties in response to various conditions. Little is known about the emergent properties of such materials. Specifically, how an individual cellular activity gives rise to collective spatiotemporal patterns is not fully understood. Recently we reported the observation of ultrafast contraction pulses in the dorsal epithelium of T.adhaerens in vivo [1] and speculated these propagate via mechanical fields. Other accumulating evidence suggest mechanics is involved in similar contractile patterns in embryonic development in vivo and in cellular monolayers in vitro. Here we show that a widespread cellular response – activation of contraction in response to stretch – is sufficient to give rise to nonlinear propagating contraction pulses. Using a minimal numerical model and theoretical considerations we show how such mechanical pulses emerge and propagate, spontaneously or in response to external stretch. The model – whose mathematical structure resembles that of reaction-diffusion systems – explains observed phenomena in T. adhaerens (e.g. excitable or spontaneous pulses, pulse interaction) and predicts other phenomena (e.g. symmetric strain profile, “spike trains”). Finally, we show that in response to external tension, such an active two-dimensional sheet lowers and dynamically distributes the strains across its surface, hence facilitating tissue resistance to rupture. Adding a cellular softening-threshold further enhances the tissue resistance to rupture at cell-cell junctions. As cohesion is at the heart of epithelial physiology, our model may be relevant to many other epithelial systems, even if manifested at different time/length scales.SignificanceOur work demonstrates that many observed dynamical phenomena in epithelial tissues can be explained merely by mechanical cell-cell interactions, and do not require chemical diffusion or transport between cells (though chemical activity may participate in relevant intracellular processes). Specifically, we show that single cell extension-induced-contraction (EIC) is sufficient to generate propagating contraction pulses, which also increase the tissue’s resistance to rupture, an essential function of epithelia. Our results may shed light on how epithelial tissues function under challenging physiological conditions, e.g. in lung, gut, vasculature and other biomedical contexts. Our results may also be relevant in the study of early evolution of multicellularity and the nervous-muscular systems. Finally, the work offers guidelines for designing soft synthetic solids with improved mechanical properties.

Aggregation of therapeutic proteins can result from a number of stress conditions encountered during their manufacture, transportation, and storage. This work shows the effects of two interrelated sources of protein aggregation: the chemistry and structure of the surface of the container in which the protein is stored, and mechanical shocks that may result from handling of the formulation. We investigated how different mechanical stress conditions (dropping, tumbling and agitation) and container surface passivation affected the stability of solutions of intravenous immunoglobulin (IVIG). Application of mechanical shock caused cavitation to occur in the protein solution, followed by bubble collapse and the formation of high-velocity fluid microjets that impinged on container surfaces, leading to particle formation. We also observed cavitation following dropping of vials from heights as low as 5 cm and that polyethylene glycol (PEG) grafting could provide temporary protection against drop-induced cavitation. PEG treatment of the vial surface reduced the formation of protein aggregates observed after repeated dropping events, most likely by reducing protein adsorption to container surfaces. These studies enable the development of new coatings and surface chemistries that can reduce the particulate formation induced by surface adsorption or/and mechanical shock.

The cytotoxicity against five human tumor cell lines (THP-1, U937, Molt-4, Colo-205 and NCI-H460) of three water soluble copper(II) coordination compounds containing the ligands 3,3'-(ethane-1,2-diylbis(azanediyl))dipropanamide (BCEN), 3,3'-(piperazine-1,4-diyl)dipropanamide (BPAP) or 3,3'-and (1,4-diazepane-1,4-diyl)dipropanamide (BPAH) are reported in this work. The ligands contain different diamine units (ethylenediamine, piperazine or homopiperazine) and two propanamide units attached to the diamine centers, resulting in N

This work demonstrates that hydrogen peroxide (H(2)O(2)) is generated in weak polyacrylamide hydrogels due to mechanochemical reactions to osmotic swelling. Hydrogels are important tools and materials for many biomedical applications, particularly for growth of stem cells. However, swollen gels are under constant tension, which makes their individual chains susceptible to mechanochemical bond breakage. In this work, an assay was developed to measure the generation of H(2)O(2) as a result of hydrogel swelling. Polyacrylamide hydrogels with both weak disulfide and strong PEG-diacrylate crosslinkers were synthesized and swelled. H(2)O(2) generation increased in the presence of weaker crosslinkers, up to 30 μM H(2)O(2), whereas stronger crosslinkers reduced this to 5 μM H(2)O(2). H(2)O(2) levels decreased when swelled in the presence of dextran to reduce osmotic stress or increased if the gels were conjugated to an acrylated surface. Finally, H(2)O(2) continued to form for days after the gels had reached their equilibrium sizes, independently of dissolved oxygen. The results of this work impact those working in the 3D cell culture community and demonstrate that even well-characterized systems undergo mechanochemical processes in mild environments.

Background Physical inactivity is associated with an increased risk of cardiovascular disease. High intensity interval training (HIIT) has been shown to improve important health parameters, including aerobic capacity, arterial blood pressure, cardiac autonomic modulation and left ventricular mechanics. However, adaptations in left atrial (LA) mechanics and aortic stiffness remain unclear. Therefore, the aim of the present study was to assess any left atrial and aortic adaptations to HIIT. Methods Forty-one physically inactive males and females (aged 23 ± 2.7 years) volunteered for the study. Participants were randomised to either a 4-week HIIT intervention (n = 21) or 4-week control period (n = 20). The HIIT protocol consisted of 3 x 30-second maximal cycle ergometer sprints with a resistance of 7.5% body weight, interspersed with 2-minutes of active unloaded recovery. Speckle tracking imaging of the left atrium and M-Mode tracing of the aorta was performed pre and post HIIT and control period using commercially available software (EchoPac; GE Medical Systems). Analysis of covariance, with baseline measures as the covariate, was used to explore any differences in left atrial mechanics and aortic stiffness between the intervention and control groups. Stepwise linear regression analysis using LA stiffness as the dependent variable was conducted. Results Following 4-weeks of HIIT, there was significant improvement in LA mechanics, including LA reservoir (13.9 ± 13.4%, p = 0.033) and LA stiffness (-0.05 ± 0.04%-1, p = 0.032) compared to the control condition. In addition, improvements were observed in aortic distensibility (2.1 ± 2.7 cm2 × dyn×-1 × 103, p = 0.031) and aortic stiffness index (-2.6 ± 4.6, p = 0.041) compared to the control condition. In stepwise linear regression analysis, aortic distensibility change was significantly associated with LA stiffness change (p = 0.002), with an R2 of 0.613. Conclusion A short-term programme of HIIT was associated with a significant improvement in LA mechanics and aortic stiffness. These adaptations may have important health implications and contribute to the improved left ventricular diastolic and systolic mechanics, aerobic capacity and reduced arterial blood pressure previously documented following HIIT.

Animals are characterized by their movement, and their tissues are continuously subjected to dynamic force loading while they crawl, walk, run or swim1. Tissue mechanics fundamentally determine the ecological niches that can be endured by a living organism2. While epithelial tissues provide an important barrier function in animals, they are subjected to extreme strains during day to day physiological activities, such as breathing1, feeding3, and defense response4. How-ever, failure or inability to withstand to these extreme strains can result in epithelial fractures5, 6 and associated diseases7, 8. From a materials science perspective, how properties of living cells and their interactions prescribe larger scale tissue rheology and adaptive response in dynamic force landscapes remains an important frontier9. Motivated by pushing tissues to the limits of their integrity, we carry out a multi-modal study of a simple yet highly dynamic organism, the Trichoplax Adhaerens10–12, across four orders of magnitude in length (1 µm to 10 mm), and six orders in time (0.1 sec to 10 hours). We report the discovery of abrupt, bulk epithelial tissue fractures (∼10 sec) induced by the organism’s own motility. Coupled with rapid healing (∼10 min), this discovery accounts for dramatic shape change and physiological asexual division in this early-divergent metazoan. We generalize our understanding of this phenomena by codifying it in a heuristic model, highlighting the fundamental questions underlying the debonding/bonding criterion in a soft-active-living material by evoking the concept of an ‘epithelial alloy’. Using a suite of quantitative experimental and numerical techniques, we demonstrate a force-driven ductile to brittle material transition governing the morphodynamics of tissues pushed to the edge of rupture. This work contributes to an important discussion at the core of developmental biology13–17, with important applications to an emerging paradigm in materials and tissue engineering5, 18–20, wound healing and medicine8, 21, 22.

In this Letter, we report that surface-bound nanobubbles reduce protein denaturation on methylated glass by irreversible protein shell formation. Single-molecule total internal reflection fluorescence (SM-TIRF) microscopy was combined with intramolecular Forster resonance energy transfer (FRET) to study the conformational dynamics of nitroreductase (NfsB) on nanobubble-laden methylated glass surfaces, using reflection brightfield microscopy to register nanobubble locations with NfsB adsorption. First, NfsB adsorbed irreversibly to nanobubbles with no apparent desorption after 5 h. Moreover, virtually all (96%) of the NfsB molecules that interacted with nanobubbles remained folded, whereas less than 50% of NfsB molecules remained folded in the absence of nanobubbles on unmodified silica or methylated glass surfaces. This trend was confirmed by ensemble-average fluorometer TIRF experiments. We hypothesize that nanobubbles reduce protein damage by passivating strongly denaturing topographical surface defects. Thus, nanobubble stabilization on surfaces may have important implications for antifouling surfaces and improving therapeutic protein storage.

Background Outcome of Mitral Valve Prolapse (MVP) was controversial for long time. Many studies reported great differences in the incidence of cardiovascular events due, above all, to heterogeneous and small studied populations. Most of theme were also published to late '80 of the last century till early '00. Purpose To make a contemporary survey on the incidence of cardiovascular events in a selected population of patients affected by primary MVP referred to a tertiary cardiovascular center for the medical and surgical care of valvular heart disease. Methods We reviewed our MVP database; patients with at least 2 cardiologic evaluations inclusive of echocardiographic examination and at least 6 months follow up were enrolled. A total of 250 patients (126 F) were selected. Their mean age was 52.1 years (ranging from 13 to 88 yo). The average follow-up time was 100 months (8,33 yrs). Results At the first medical and echocardiographic examination 8 patients (3,2%) had no mitral regurgitation (MR), 104 (41.6%) have a trace/mild MR, 93 (37,2%) a moderate MR and 46 (18,4%) a severe MR. They were widely asymptomatic (NYHA I 205-82%, NYHA II 44-17.60%, NYHA III 1- 0.40%). Most of theme presented a bileaflet (140-55.8%) or a posterior MVP (94 - 37.6%); an isolated anterior MVP was rare (16 - 6,4%). Flail leaflet was present in 8 (3,2%) and 25 (10%) had a chordal rupture. Respectively 165 (65,6%) and 115 (46,1%) patients had thick and redundant leaflets. Mean antero-posterior mitral annulus diameter was 37 mm. During the follow up 7 patients died of non-cardiac cause and 5 (2%) of suspected cardiac cause (2 because of acute coronary syndrome and 3 died suddenly). MR progresses in 43 (17,2%) patients and finally we observed 81 (32,4%) moderate/severe and severe MR. 12 new chordal rupture occurred during the follow up in most cases concerning mitral chordae linked to posterior mitral leaflet (10 cases-83,3%). The worsening of MR provoked an evolution of the clinical condition of 48 patients (19.2%) which developed Dyspnea On Excertion (DOE) with 42 new NYHA II and 6 new NYHA III. At the end of the follow up the amount of patients symptomatic for DOE was 93 (37.2% vs 18% at the initial evaluation). A total of 45 patients (18%) underwent mitral valve surgery. 40 needed in-hospital treatment in most cases due to the development of atrial fibrillation (19 -7.6%) or heart failure ( 8- 3,2%). Endocarditis occurred in 4 patients (1.6%) and cerebrovascular accidents/cardioembolic event in 6 (2.4%). The overall cardiovascular event rate was 4,33/100 patients-year, significantly higher than reported in community based studies. Conclusions The prognosis of a MVP population referred to a tertiary cardiovascular center is not benign. The most frequent complications are progression of MR and MV surgery. Sudden death is also more frequent than in general population. More studies are needed to identify what patients with MVP are at risk for it.

We investigated the antineoplastic activities of a previously reported copper (II) coordination compound, [Cu(BMPA)Cl2]CH3OH (1), and a new compound, [Cu(HBPA)Cl2]H2O (2), where BMPA is bis(pyridin-2-ylmethyl)amine and HBPA is (2-hydroxybenzyl)(2-pyridylmethyl)amine, using various cellular models of human leukemia (THP-1, U937, HL60, Molt-4, JURKAT) and human colon cancer (COLO 205), as well as a murine highly metastatic melanoma (B16-F10) cell line. Compound (2) was characterized using several physical and chemical techniques, including X-ray diffraction studies. The IC50 values of the copper coordination complexes in the human leukemia cell lines ranged from 87.63 ± 1.02 to ≥400 μM at high cell concentrations and from 19.17 ± 1.06 to 97.67 ± 1.23 μM at low cell concentrations. Both compounds induced cell death, which was determined by cell cycle analyses and phosphatidylserine exposure studies. THP-1 cells released cytochrome c to the cytoplasm 12 h after treatment with 400 μM of compound (2). To evaluate the apoptosis pathway induced by compound (2), we measured the activities of initiator caspases 8 and 9 and executioner caspases 3 and 6. The results were suggestive of the activation of both intrinsic and extrinsic apoptosis pathways. To investigate the activities of the compounds in vivo, we selected two sensitive cell lines from leukemia (THP-1) and solid tumor (B16-F10) lineages. BALB/c nude bearing THP-1 tumors treated with 12 mg·kg−1 of compound (2) showed a 92.4% inhibition of tumor growth compared with the control group.

The synthesis, physico-chemical characterization and cytotoxicity against five human tumoral cell lines (THP-1, U937, Molt-4, Colo205 and H460) of three new cobalt(II) coordination compounds are reported (i.e. Co(HL1)Cl (1), Co(HL2)Cl (2) and [Co(HL3)Cl]0.0.5 (CH3)2CHOH (3)). H2L2 (2-{[[2-hydroxy-3-(1-naphthyloxy)propyl](pyridin-2-ylmethyl)amino]methyl}phenol) and H2L3 (2-{[[2-hydroxy-3-(2-naphthyloxy)propyl](pyridin-2-ylmethyl)amino]methyl}phenol) present α and β-naphthyl groups respectively, which is absent in H2L1 (N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]propylamine. These compounds were characterized by a range of physico-chemical methods. X-ray diffraction studies were performed for complex (3), indicating the formation of a mononuclear complex. Complexes (2) and (3), which contain α and β-naphthyl groups respectively, have presented lower IC50 values than those exhibited by complex (1). Complex (3) presents IC50 values lower than cisplatin against Colo205 (90 and 196μmolL(-1), respectively) and H460 (147 and 197μmolL(-1), respectively). These human neoplastic cells under investigation were also more susceptible toward complex (3) than peripheral blood mononuclear cells. Transmission electron microscopy investigations are in agreement with the loss of mitochondrial membrane potential (ΔΨm) observed by JC-1 mitochondrial potential sensor and indicate that the activity of complex (3) against leukemic cell line (U937) is mediated by an apoptotic mechanism associated with mitochondrial dysfunction (intrinsic pathway).

The aim of our study was to evaluate the in vitro and in vivo anti-proliferative potential of complex (2) [Cu (L1)Cl]Cl.2H2O, where L1 = 1-[2-hydroxybenzyl(2-pyridylmethyl)amino]-3-(1-naphthyloxy)-2-propanol on lung carcinoma cell NCI-H460. Cell viability assay determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay demonstrated that the complex (2) exhibits higher activity against the NCI-H460 cell, with an IC50 value lower than cisplatin (26.5 μM ± 1.1 and 203 ± 1.2 μM respectively). Cell death by apoptosis was investigated by flow cytometer analysis of sub-G1 populations in the cell cycle and Annexin V/Propidium Iodide assay. Changes on the cell surface and ultrastructure were detected by scanning and transmission electron microscopy. Our work revealed that complex (2) induced changes associated with apoptosis, such as plasma membrane blebbing and a lower microvilli amount, fragmentation and condensation of chromatin, alterations in mitochondria, and enlargement of the endoplasmic reticulum. Mitochondrial function of NCI-H460 cells evaluated by 5,5′,6,6′-tetrachloro 1,1′,3,3′ tetraethylbenzimidazolylcarbocyanine iodide (JC-1) probes showed high loss of mitochondrial membrane potential when treated with complex (2). Moreover, caspase-12 measurement showed an expressive activation level, which is related to endoplasmic reticulum stress. In vivo assay using the murine model of human lung cancer cell showed that complex (2) and cisplatin has similar antineoplastic activity.

By definition of multicellularity, all animals need to keep their cells attached and intact, despite internal and external forces. Cohesion between epithelial cells provides this key feature. To better understand fundamental limits of this cohesion, we study the epithelium mechanics of an ultrathin (∼25 μm) primitive marine animal Trichoplax adhaerens , composed essentially of two flat epithelial layers. With no known extracellular matrix and no nerves or muscles, T. adhaerens has been claimed to be the “simplest known living animal,” yet is still capable of coordinated locomotion and behavior. Here we report the discovery of the fastest epithelial cellular contractions known in any metazoan, to be found in T. adhaerens dorsal epithelium (50% shrinkage of apical cell area within one second, at least an order of magnitude faster than other known examples). Live imaging reveals emergent contractile patterns that are mostly sporadic single-cell events, but also include propagating contraction waves across the tissue. We show that cell contraction speed can be explained by current models of nonmuscle actin–myosin bundles without load, while the tissue architecture and unique mechanical properties are softening the tissue, minimizing the load on a contracting cell. We propose a hypothesis, in which the physiological role of the contraction dynamics is to resist external stresses while avoiding tissue rupture (“active cohesion”), a concept that can be further applied to engineering of active materials.

Background Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results A random subcohort of 349 participants was selected from the DCCT / EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT , and 1 to 2 years post‐ DCCT ( EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F 2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F 2α . Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F 2α , an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P iso prostaglandin F 2α , P =0.0092). In contrast, the oxidative markers myeloperoxidase and F 2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Conclusions Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 00360815 and NCT 00360893.

The crystal structure of [Cu(HBPA)2]Cl2·4H2O [HBPA = (2-hydroxybenzyl-2-pyridylmethyl)amine] revealed an octahedral geometry around Cu(II). The mononuclear complex crystallizes in the triclinic space group P21/n with cell lengths of a = 7.3705 (6), b = 9.7695 (6), c = 20.2314 (15) A and with cell angles of α = 90, β = 100.264 (3) and γ = 90o. The coordination plane is comprised of two secondary amine and two pyridine nitrogens, the phenol oxygen atoms are coordinated in the protonated form and occupy the axial sites. Investigations in solution (MeOH and DMF) by electronic spectroscopy and electrochemical studies suggest effect of the solvents on the structure, indicating the partial coordination of the axial ligands as phenolate, resulting in the formation of distinct species in solution. Addition of base enables the effective coordination of phenol group as phenolate, as observed by the increase of the intensity of the band at 429 nm and the formation one only compound in DMF solution, according to cyclic voltammetry studies. Herein we describe the crystal structure of [Cu(HBPA)2]Cl2·4H2O [HBPA = (2-hydroxybenzyl-2-pyridylmethyl)amine].The coordination plane is comprised of two secondary amine and two pyridine nitrogens, the phenol oxygen atoms are coordinated in the protonated form and occupy the axial sites. Investigations in solution by electronic spectroscopy and electrochemical studies suggest effect of the solvent; the addition of base enables the effective coordination of phenol group as phenolate, resulting in one only compound in solution.

Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is widely used to mechanically measure the folding and unfolding of proteins. However, the temporal resolution of a standard commercial cantilever is 50-1000 μs, masking rapid transitions and short-lived intermediates. Recently, SMFS with 0.7-μs temporal resolution was achieved using an ultrashort (L = 9 μm) cantilever on a custom-built, high-speed AFM. By micromachining such cantilevers with a focused ion beam, we optimized them for SMFS rather than tapping-mode imaging. To enhance usability and throughput, we detected the modified cantilevers on a commercial AFM retrofitted with a detection laser system featuring a 3-μm circular spot size. Moreover, individual cantilevers were reused over multiple days. The improved capabilities of the modified cantilevers for SMFS were showcased by unfolding a polyprotein, a popular biophysical assay. Specifically, these cantilevers maintained a 1-μs response time while eliminating cantilever ringing (Q ≅ 0.5). We therefore expect such cantilevers, along with the instrumentational improvements to detect them on a commercial AFM, to accelerate high-precision AFM-based SMFS studies.