This study investigates whether a chronotherapeutic treatment of hepatocellular carcinoma (HCC) may improve treatment efficacy and mitigate side effects on healthy liver (HL). HCC was induced in Per2::luc mice which were irradiated at four time points of the day. Proliferation and DNA-double strand breaks were investigated in irradiated and non-irradiated organotypic slice culture (OSC) and ex vivo samples by detection of Ki67 and γ-H2AX. OSC proved useful to determine dose-dependent effects on proliferation and DNA damage but appeared unsuited to test the chronotherapeutic approach. Irradiation of ex vivo samples was most effective at the proliferation peaks in HCC at ZT02 (early inactivity phase) and ZT20 (late activity phase). Irradiation effects on HL were minimal at ZT20. Ex vivo samples revealed disruption in daily variation and down-regulation of all investigated clock genes except Per1 in non-irradiated HCC as compared with HL. Irradiation affected rhythmic clock gene expression in HL and HCC at all ZTs except at ZT20. Irradiation at ZT20 had no effect on total leukocyte numbers. Our results indicate ZT20 as the optimal time point for irradiation of HCC in mice. Translational studies are now needed to evaluate whether the late activity phase is the optimal time point for irradiation of HCC in man.

Fusarium culmorum is a major pathogen of grain crops. Infected plants accumulate deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), or nivalenol (NIV), which are mycotoxins of the trichothecene B group. These toxins are also produced by F. graminearum species complex. New trichothecenes structurally similar to trichothecenes B but lacking the carbonyl group on C-8, designated NX toxins, were recently discovered in atypical isolates of F. graminearum from North America. Only these isolates and a few strains of a yet to be characterized Fusarium species from South Africa are known to produce NX-2 and other NX toxins. Here we report that among 20 F. culmorum strains isolated from maize, wheat, and oat in Europe and Asia over a period of 70 years, 18 strains produced NX-2 simultaneously with 3-ADON and DON or NIV. Rice cultures of strains producing 3-ADON accumulated NX-2 in amounts corresponding to 2-8% of 3-ADON (1.2 - 36 mg/kg). A strain producing NIV accumulated NX-2 and NIV at comparable amounts (13.6 and 10.3 mg/kg, respectively). In F. graminearum, producers of NX-2 possess a special variant of cytochrome P450 monooxygenase encoded by TRI1 that is unable to oxidize C-8. In F. culmorum, producers and nonproducers of NX-2 possess identical TRI1; the reason for the production of NX-2 is unknown. Our results indicate that production of NX-2 simultaneously with trichothecenes B is a common feature of F. culmorum.

The number of published studies on curcuminoids in cancer research, including its lead molecule curcumin and synthetic analogs, has been increasing substantially during the past two decades. Insights on the diversity of inhibitory effects they produced on a multitude of pathways involved in carcinogenesis and tumor progression were provided. As this wealth of data was obtained in a setting of various experimental and clinical data, this review first aimed at presenting a chronology of discoveries and an update on their complex in vivo effects. Secondly, there are many interesting questions linked to their pleiotropic effects. One of them, which is a growing research topic, relates to their ability to modulate metabolic reprogramming. This review will also cover the use of curcuminoids as chemosensitizing molecules, that can be combined with several anticancer drugs for reversing the phenomenon of multidrug resistance. Finally, current investigations in these three complementary research fields raise several important questions that will be put in the prospects for the future research related to the importance of these molecules in cancer research.

The molecular mechanisms underlying insect gall formation remain unclear. A major reason for the inability to identify the responsible genes is that most insect galls are produced on woody plants and therefore cannot be experimentally validated in the laboratory. To overcome these problems, we established a new galling insect model, Smicronyx madaranus. Our manipulation experiments using nail polish sealing and insecticide treatment revealed an age-dependent change in gall formation during S. madaranus; adult females and larvae are responsible for gall induction and enlargement, respectively. Furthermore, it has been suggested that substances released during oviposition and larval feeding are involved in each process. Phylogenetic analysis showed that most gall-forming weevils, including S. madaranus, belong to a single lineage, suggesting that gall-forming traits evolved in a specific lineage within Smicronyx. The efficacy of RNA interference (RNAi) in S. madaranus was confirmed by targeting multicopper oxidase 2 gene. It is expected that the mechanisms of gall formation will be elucidated by a comprehensive functional analysis of candidate genes using RNAi and the S.madaranus galling system in the near future.

With the increasing use of data-driven modeling methods new approaches to complex problems in the field of wind energy can be addressed. Topics reviewed through literature include wake modeling, performance monitoring and controls applications, condition monitoring and fault detection, and other data-driven research. Literature shows the advantages of data-driven methods reduce computational expense or complexity, particularly in the cases of wake modeling and controls, as well as various data-driven methodologies’ aptitude for predictive modeling and classification, as in the cases of fault detection and diagnosis. Significant work exists for fault detection while less work is found for controls applications. A methodology for creating data-driven wind turbine models for arbitrary performance parameters is proposed. Results are presented utilizing the methodology to create wind turbine models relating active adaptive twist to steady-state rotor thrust as a performance parameter of interest. Resulting models are evaluated by comparing root-mean-square-error (RMSE) on both the training and validation data sets, with Gaussian Process Regression (GPR), deemed an accurate model for this application. The resulting model undergoes particle swarm optimization to determine the optimal aerostructure twist shape at a given wind speed with respect to the modeled performance parameter, aerodynamic thrust load. The optimization process shows an improvement of 3.15% in thrust loading for the 10 MW reference turbine, and 2.66% for the 15 MW reference turbine.

X-ray Fluorescence Computed Tomography (XFCT) is an emerging non-invasive imaging technique providing molecular-level data, gaining attention for high-resolution imaging. However, increased sensitivity with benchtop X-ray sources raises radiation exposure. Artificial Intelligence (AI), particularly deep learning (DL), has revolutionized medical imaging by delivering high-quality images in the presence of noise. In XFCT, traditional methods rely on complex algorithms for noise reduction, but AI holds promise in addressing high-dose concerns. We present an optimized SCUNet model for noise reduction in low-concentration XRF images. Compared to higher-dose images, our method’s effectiveness is evaluated. While various denoising techniques exist for X-ray and CT, few address to XFCT. The DL model is trained and assessed using the augmented data, focusing on background noise reduction. Image quality is measured using PSNR and SSIM, comparing outcomes with 100% X-ray dose images. Results show the proposed algorithm achieves high-quality images from low-dose and low-contrast agents, with a maximum PSNR of 39.05 and SSIM of 0.86. The model outperforms BM3D, NLM, DnCNN, and SCUNet in both visual inspection and quantitative analysis, particularly in high-noise scenarios. This indicates the potential of AI, specifically the SCUNet model, in significantly improving XFCT imaging by mitigating the trade-off between sensitivity and radiation exposure.

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. The role of dysfunctional mitochondria in psychopathology is well-established, however, the association of these organelles with sleep physiology is novel. Indeed, reducing neuronal oxidative stress by importing mitochondria from astrocytes, may be the purpose of human slumber. This model may explain mitochondrial dysfunction during anesthesia as well as in the rare genetic disease, fatal familial insomnia. In this narrative review, we focus on the salience network of the brain, a common denominator for insomnia, neuropsychiatric and neurodegenerative disorders. We also discuss mitochondria-protecting strategies, including membrane lipid replacement, natural and synthetic phenazine and phenothiazine derivatives.

Daily maximum surface air temperature (Tamax) is a crucial factor for understanding complex land surface processes under rapid climate change. Remote detection of Tamax has widely relied on the empirical relationship between air temperature and land surface temperature (LST), a product derived from remote sensing. However, little is known about how such a relationship is affected by the high heterogeneity in landscapes and dynamics in seasonality. This study aims to advance our understanding of the roles of land cover and seasonal variation in the estimation of Tamax using the MODIS (Moderate Resolution Imaging Spectroradiometer) LST product. We developed statistical models to link Tamax and LST in the middle and lower reaches of the Yangtze River in China for five major land-cover types (i.e., forest, shrub, water, impervious surface, cropland, and grassland) and two seasons (i.e., growing season and non-growing season). Results show that the performance of modeling the Tamax-LST relationship was highly dependent on land cover and seasonal variation. Estimating Tamax over grasslands and water bodies achieved superior performance; while uncertainties were high over forested lands that contained extensive heterogeneity in species types, plant structure, and topography. We further found that all the land-cover specific models developed for the plant non-growing season outperformed the corresponding models developed for the growing season. Discrepancies in model performance mainly occurred in the vegetated areas (forest, cropland, and shrub), suggesting an important role of plant phenology in defining the statistical relationship between Tamax and LST. For impervious surfaces, the challenge of capturing the high spatial heterogeneity in urban settings using the low-resolution MODIS data made Tamax estimation a difficult task, which was especially true in the growing season.

In a previous work by the author it was shown that the Koopman-von Neumann formulation of classical mechanics (KvN) exhibits quantum interference. As such it was there claimed that KvN ought to be considered as a proper quantum mechanical theory in a similar sense as ordinary non-relativistic quantum mechanics (OQM) is. In this article this claim is made manifest by showing that KvN and OQM can be taken as merely inequivalent representations resulting from one and the same quantization scheme. Of course, as the typical notion of quantization necessitates the canonical commutation relations (CCR) to hold, which they do not in KvN, the concept needs to be properly revised. To justify such a revision the typical reasons for necessitation the CCR, reductionism and quantization as 'turning brackets to commutators', are examined and found insufficient.

Galls are characteristic plant structures formed by cell size enlargement and/or cell proliferation induced by parasitic or pathogenic organisms. Insects are a major inducer of galls, and insect galls can occur on plant leaves, stems, floral buds, flowers, fruits, or roots. Many of these exhibit unique shapes, providing shelter and nutrients to insects. To form unique gall structures, gall-inducing insects are believed to secrete certain effector molecules and hijack host developmental programs. However, the molecular mechanisms of insect gall induction and development remain largely unknown due to the difficulties associated with the study of non-model plants in the wild. Recent advances in next-generation sequencing have allowed us to determine the biological processes in non-model organisms, including gall-inducing insects and their host plants. In this review, we first summarize the adaptive significance of galls for insects and plants. Thereafter, we summarize recent progress regarding the molecular aspects of insect gall formation.

Aortic stenosis (AS) is a prevalent valvular disorder that often requires surgical aortic valve replacement (SAVR) to alleviate symptoms and improve survival. However, the selection of an appropriate prosthetic valve size is crucial to avoid patient-prosthesis mismatch (PPM), which can lead to suboptimal hemodynamic outcomes. Von Willebrand factor (VWF), a key component of hemostasis, has been shown to be altered in AS patients and may contribute to the hemostatic imbalance observed following valve replacement. This prospective study aimed to investigate the impact of PPM on postprocedural VWF levels in patients undergoing SAVR for severe AS. The study included 31 consecutive patients diagnosed with severe AS who underwent SAVR. By focusing on the relationship between PPM and VWF dynamics, this study sought to provide valuable insights into the potential role of VWF as a marker for hemostatic changes associated with PPM, ultimately informing strategies for optimal valve selection and perioperative management to minimize complications.

The frequency of selected polymorphisms, one in each gene coding for proteins with antioxidative properties (CAT, SOD2, GPX1, NQO1) was compared between patients suffering from pain-related temporomandibular disorders (TMDp;n=85) and control subjects (CTR;n=85). According to the Oral Behaviours Checklist score participants were divided into high-frequency parafunction (HFP;n=98) and low-frequency parafunction (LFP;n=72) groups. In addition, we have investigated the association of selected polymorphisms with participants' psychological (anxiety, depression) and psychosomatic (hypervigilance, somatosensory amplification) characteristics. Polymorphisms rs1001179, rs4880, rs1050450, rs689452 were genotyped using the genomic DNA extracted from buccal mucosa swabs and real-time TaqMan genotyping assays. No differences in genotype distribution between TMDp patients and control subjects were found. Still, TMDp patients who were homozygous for minor allele A, related to the GPX1 polymorphism rs1050450 reported significantly more waking-state oral behaviours compared to GA+GG genotype carriers (score: 30 vs. 23, p=0.019). Frequency of genotype AA for rs1050450 polymorphism was higher in HFP compared to LFP participants (14.3% vs. 4.2%, p =0.030). Most important predictors of waking-state oral behaviours were depression, anxiety, AA genotype (rs1050450) and female sex. Explored genetic factors were not found to be significant risk factors for either TMDp or sleep-related oral behaviours. The association of waking-state oral behaviours with selected gene polymorphisms additionally supports previous assumptions that the daytime bruxism is more closely linked to various stress manifestations, which might also be reflected through the variability related to cellular antioxidative activity.

Over the past two decades, persistent occurrences of harmful algal blooms (HAB; Karenia brevis) have been reported in Charlotte County, southwestern Florida. We developed data-driven models that rely on spatiotemporal remote sensing and field data to identify factors controlling HAB propagation, provide a same-day distribution (nowcasting), and forecast their occurrences up to three days in advance. We constructed multivariate regression models using historical HAB occurrences (213 events reported from January 2010 to October 2017) compiled by the Florida Fish and Wildlife Conservation Commission and validated the models against a subset (20%) of the reported historical events. The models were designed to specifically capture the onset of the HABs instead of those that developed days earlier and continued thereafter. A prototype of an early warning system was developed through a threefold exercise. The first step involved the automatic downloading and processing of daily Moderate Resolution Imaging Spectroradiometer (MODIS) Aqua products using SeaDAS ocean color processing software to extract temporal and spatial variations of remote sensing-based variables over the study area. The second step involved the development of a multivariate regression model for same-day mapping of HABs and similar subsequent models for forecasting HAB occurrences one, two, and three days in advance. Eleven remote sensing variables and two non-remote sensing variables were used as inputs for the generated models. In the third and final step, model outputs (same-day and forecasted distribution of HABs) were posted automatically on a web-based GIS (http://www.esrs.wmich.edu/webmap/bloom/). Our findings include the following: (1) the variables most indicative of the timing of bloom propagation are bathymetry, euphotic depth, wind direction, SST, chlorophyll-a [OC3M] and distance from the river mouth, and (2) the model predictions were 90% successful for same-day mapping and 65%, 72% and 71% for the one-, two- and three-day advance predictions, respectively. The adopted methodologies are reliable, dependent on readily available remote sensing data sets, and cost-effective and thus could potentially be used to map and forecast algal bloom occurrences in data-scarce regions.

BackgroundThe clean energy transition required for decarbonisation of our societies make policymakers targets for broad business and non-business advocacy to ensure one’s often conflicting interests are protected or taken into consideration in public policies. The concept of policy entrepreneurs foregrounds the role of agency in understanding such acts of advocacy. This paper compares strategies used by policy entrepreneurs from different social spheres, advocating policy change or status quo, in four longitudinal cases related to European Union energy and climate policy 2011–2023. ResultsPolicy entrepreneurship was mainly of a cultural-institutional nature, aiming at altering or diffusing people’s perceptions, beliefs, norms and cognitive frameworks, worldviews, or institutional logics. But the actions of the European Commission did also include structural entrepreneurship, aiming at overcoming structural barriers to enhance governance influence by altering the distribution of formal authority and factual and scientific information. Motifs of policy entrepreneurs in the four cases differ, but strategies do not differ significantly between the public, private and civic spheres of society. Results indicate that civil society policy entrepreneurs focus on building broader coalitions than public and private sector entrepreneurs. There is no indication that policy entrepreneurs from a certain sector would be more successful than others in setting the agenda, changing perceptions of policy actors, or influencing actual policy change. However, policy entrepreneurs advocating policy change are more active and use more elaborated strategies than policy entrepreneurs advocating status quo. ConclusionsIt is concluded that policy entrepreneurs advocating policy change are more active and use more elaborated strategies than policy entrepreneurs advocating status quo. Thus, they are more successful in influencing policy outcomes. The European Commission was the only policy entrepreneurs to use structural entrepreneurship. the Commission acts to expand its reach into areas where the European Union does not hold much legal competence according to the constitution of the European Union. This comes with democratic deficits related to accountability and legitimacy and should be combated to reinstate and reinforce the position and powers of both the national and European legislators in taking the important decisions that impact the lives of European citizens.

The questions on who is entitled to benefit from REDD+ transactions remains one of the most controversially debated issues around cooperative efforts to reduce deforestation in developing countries. REDD+ has been conceived as international framework for voluntary efforts of developing countries to reduce greenhouse gas emissions and enhance carbon removals from forest activities. Designed as international framework under the UNFCCC that calculates emission reductions and removals (ERRs) at the national -and as an interim step on the subnational level – REDD+ is primarily a creature of international law. However, in defining forest-carbon ERRs the international framework competes with national emission trading systems and domestic REDD+ legislation as well as private standards that define units traded on the voluntary carbon market. The definition of various carbon units is closely linked to the question on who is entitled to participate in REDD+ and benefit from the sale of ERRs under results-based payment schemes or carbon market transactions. This paper applies a legal lens to the various claims to participate in REDD+ transactions. It tries to disentangle the various rights to ERRs, various carbon credits, and payments that come with REDD+ and that almost always create confusion and not seldom conflict around REDD+ implementation. The definition of carbon rights and the legal nature of carbon credits depends on local law and differs between countries. However, there are a number of legal considerations that apply and certain underlying concepts are relevant for the understanding of REDD+ transactions and the allocation of benefits and burdens of conservation activities.

The concept of policy entrepreneurs has gained increasing attention in studies of climate policy and governance since it foregrounds the role of agency in understanding policy change. However, agency of policy entrepreneurs in the policy process is largely political and conceals the power that shapes how public problems and policies are framed and defined. Thus, policy entrepreneurs should be confronted with the challenge of generating legitimacy, accountability and justice of their actions and the implementation of their targeted policy change. Drawing on political-philosophical theories of liberal and deliberative democracy this paper outlines a conceptual framework for critical analytical as well as normative research on strategies and impacts of policy entrepreneurs. Empirical research on the strategies and impacts of policy entrepreneurs in recent policymaking on climate policy and governance in the EU and Sweden identifies several democratic deficits. In all, the paper brings ideology and politics into research on policy entrepreneurs. It is suggested that not only the strategies used, but also the ideologies of actors that use them, is the causal mechanism that links the policy entrepreneurs to the outcomes, and thus if their advocacy will facilitate or hamper a just transition to climate neutrality and sustainability.

Three new species of genus Caridina are described from the northernmost part of Australia. Caridina darwin n. sp. resembles Caridina temasek Choy & Ng, 1991 from Singapore but differs in the armature of the rostrum, development of epipods on pereiopods and in lacking an appendix interna on male´s first pleopods. Caridina magnovis n. sp. resembles Caridina serratirostris de Man, 1892 but differs from this species in the armature of the ventral margin of the rostrum, a shorter stylocerite, a stouter carpus of first pereiopod, number and size of spiniform setae on third and fifth pereiopods, the shape of the preanal carina and in egg size. Caridina wilsoni n. sp. resembles Caridina gracilirostris de Man, 1892 but differs in egg size and some length to wide ratio of segments of the pereiopods. Detailed morphological descriptions of all three new species are given. A molecular phylogeny (mt DNA 16S) supports the morphospecies hypotheses and illustrates the phylogenetic relationship with morphologically similar species from outside Australia.

In this paper I dig deep down along the slope of what touches me deeply – a democratic decline in climate politics. I follow the course of critical researchers in management and organisation studies, striving to move away from traditional, horizontal norms of academic writing that focus on counting rather than content and elision the author from the text, towards a more vertical writing acknowledging the value of incorporating the voice of the author. Embodying and resonating with my own emotional experiences of hate and threat campaigns, not locking my own vulnerabilities in, I analyse qualitatively the use, reasons, contents, senders and targets of such nasty rhetoric in Swedish climate politics, and the implications thereof for democracy. At the moment, a far-right populist nativist party holds tangible powers dictating the content and process of Swedish climate politics. In less than two years, Swedish climate politics have turned into an antidemocratic divisive politics portraying climate science as “a point of view”, female journalists writing about climate change and climate policy as “crypto environmentalists”, “motherfuckers” and “moron hags” that should be “fired” and “raped”, and the climate justice movement as “terrorists” and “a threat to Swedish democracy” that should be “sent to prison” and “executed”. Such nasty rhetoric is used not only by anonymous trolls in social media, but by the prime minister, cabinet ministers and parliamentarians, even in debates in the Swedish parliament. It has inspired the far-right extremist movement to use physical violence. Use of nasty politics aims to silence the opponents to the government’s climate policy, the political opposition, climate scientists, the climate justice movement and journalists, breaching liberal and deliberative democratic norms such as legitimacy, accountability and justice. It is a powerful tactic that leaves its targets with an anxious fear of losing control and often a need for disappearance. Many targets resign or stay silent. I chose to break the silence and write differently about the issue.

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

A techno-economic model was developed to investigate the influence of components on the system costs of redox flow batteries. Sensitivity analyses were carried out based on a example of a 10 kW/120 kWh vanadium redox flow battery system and the costs of the individual components were analyzed. Particular consideration was given to the influence of material costs and resistances of bipolar plates and energy storage media as well as voltages and electric currents. Based on the developed model it was possible to formulate statements about the targeted optimization of existing battery systems and general aspects for future developments of redox flow batteries.

Thermal variations affect tri-trophic interactions involving plants, herbivores, and parasitoids, causing a mismatch between their phenological cycles. In the current environmental context of climate change, climatic factors can undergo profound and sudden changes, such as sudden hot or cold snaps. Here we show that episodes of short but sustained low temperatures have increased, mainly in the month of May, in the last two decades. We subjected galls induced by Asian chestnut gall wasp (ACGW) Dryocosmus kuriphilus to cold stress to assess if and how the pest and its parasitoids were affected. Over the course of two years seasonal parasitism, parasitism rates, the relative abundance of each parasitoid species, and mortality of ACGW were calculated. We found that the cold treatment affected both pest and parasitoids, resulting in a reduction in emerging ACGWs and differing ratios of species within the parasitoid community. The striking example was the change in the relative frequency of three species of Eupelmus spp. and of Mesopolobus tibialis, which doubled in thermally-stressed galls in all chestnut fields. The thermal effects on the development of the host and the direct effects of cold temperatures on the surface of galls (i.e., humidity or hardness of the galls) warrant further research in this direction.

Sweden has long been hailed as a role model in climate policy. But the new right-wing government supported by a far-right populist party is undertaking a paradigm shift in Swedish climate policy and governance. This paper critically analyses this paradigm shift and its impacts on legitimacy, accountability and justice. These are democratic norms important in the analysis of a just transition to climate neutrality. Severe democratic deficits of the policy process and the policies proposed and adopted are identified, suggesting ‘nasty politics’ characterised by populist, divisive, and contentious rhetoric that entrenches polarization and us/them narratives. Climate scientists and the climate justice movement are discriminated in the policy process, the latter also being accused of terrorism and seen as a threat to democracy by the government. The deficits are partly explained by the neo-corporatist political system of Sweden and the dominance of the (neo)liberal discourse of ecological modernization in Swedish environmental policy, but primarily with the ongoing process of autocratization driven by anti-democratic far-right populist parties throughout Europe. The anti-democratic climate policy reforms in Sweden are foreboding an unwelcome development in the EU given the boost of far-right populist parties in the upcoming elections to the European Parliament in June 2024.

Sweden has long been hailed as a role model in climate policy. But the new right-wing government supported by a far-right populist party is undertaking a paradigm shift in Swedish climate policy and governance. This paper critically analyses this paradigm shift from perspectives of legitimacy, accountability and justice. These are democratic norms important in the analysis of a just transition to climate neutrality. Severe democratic deficits of the policy process and the policies proposed and adopted are identified. The deficits are explained by the neo-corporatist political system of Sweden, the dominance of the (neo)liberal discourse of ecological modernization in Swedish environmental policy, and an ongoing process of autocratization driven by anti-democratic far-right populist parties throughout Europe. The paper ends by suggesting how climate policy and governance can be democratized and re-politicized, that also give room for climate justice advocates to take part in policy processes.

This research explores the influence of nationality and financial literacy on satisfaction with neobank services among university students. Through a comparative analysis between German and international students, the study unveils that international students exhibit significantly higher satisfaction levels, suggesting that cultural differences and the requirement for international financial services play a crucial role Oishi et al., 1999. Although financial literacy was anticipated to have a strong impact, its effect on satisfaction did not reach statistical significance, indicating a nuanced relationship. This perhaps because the study sample of students partaking in the survey was mostly Graduate students in the field of Economics, Finance and Management. Demographic factors such as gender and age were found to be less influential compared to nationality and financial acumen Gelfand et al., 2011. These findings highlight the importance of tailored financial services and the potential of financial education in enhancing neobank satisfaction Gerrans et al., 2014. The study contributes to the understanding of consumer behavior in digital banking, offering insights for neobanks aiming to improve service adoption and customer loyalty within the university student demographic.

EU politics on decarbonizing shipping is an argumentative struggle in which actors try to make others see the problem and policy solutions according to their views and seek to position other actors in a specific way. This article critically analyses, by means of argumentative discourse analysis, the politics and policy process related to the recent adoption of the FuelEU Maritime regulation, the world’s most ambitious legislation for decarbonizing maritime shipping. Different storylines and discourses as well as agency of policy actors on the problems and policy options defining the meaning of decarbonization are analysed. Two discourses framed the debates, focusing on (i) incremental change and technology neutrality to meet moderate emission reductions and maintain competitiveness, and (ii) transformative change and technology specificity to meet zero emissions and gain competitiveness and global leadership in the transition towards a hydrogen economy. Policy actors successfully used discursive agency strategies such as multiple functionality and vagueness to navigate between and resolve conflicts between the two discourses. Both discourses are associated with the overarching ecological modernization discourse and failed to include issue of a just transition. The heritage of the ecological modernization discourse creates lock-ins for a broader decarbonization discourse, thus stalling a just transition.

This article proposes a novel formulation of quantization, which considers the Koopman-von Neumann formulation (KvN) and ordinary non-relativistic quantum mechanics (OQM) as unitarily inequivalent representations of the same underlying structure. The approach is grounded in the notion that contextuality, rather than occurrence if Plank's constant, is the fundamental aspect of quantum mechanics. The motivation for this novel view arises from the limitations of traditional approaches to quantization, combined with previous research demonstrating contextuality in KvN. Using a representation-theoretic approach, both KvN and OQM are regarded as valid quantum theories, separated by a superselection rule.

Von Hippel-Lindau disease (VHL) is a multiple organ neoplastic syndrome with autosomal dominant transmission, complete penetrance, and variable expression caused by mutations in the VHL gene. Although VHL disease is hereditary in many cases, new mutations cause up to 20 % of the incidence. Mutations in VHL may cause the development of cysts and tumors in many organs, including brain and spinal cord hemangioblastoma, renal cell carcinoma (RCC), retinal heman-gioblastoma (RH), pheochromocytoma, epididymal and broad ligament cystadenomas, endo-lymphatic sac tumor, pancreatic neuroendocrine tumors, and renal and pancreatic cysts. VHL is a syndrome associated with functional inactivation of the Von Hippel–Lindau protein (pVHL). pVHL is a tumor suppressor mainly known for its role as a regulator of hypoxia-inducible factor (HIF) activity. The prevalence of VHL disease is between 1 in 39 000 and 1 in 91 000 individuals in different regional populations. Here, we review the etiology, epidemiology, pathophysiology, genetics, clinical manifestations, diagnosis, and current treatments, as well as the molecular aspects of this disease. We also discuss the animal models used to study this disease, VHL biomarkers, and current VHL clinical trials for VHL according to NIH.

1) Background: Patients with neurological disorders are particularly at risk of falling and requiret functional rehabilitation. HUBER® is a motorised rotating platform that allows simultaneous work on balance, stability and strength with continuous adaptation and immediate feedback. This study aimed to measure the impact of rehabilitation with the HUBER® on the physical performance and quality of life of patients with neurological diseases requiring functional rehabilitation. 2) Methods: 32 subjects were enrolled in CHU Liège CNRF and randomly divided into 2 groups. The first group received classical rehabilitation combined with two training sessions per week on the HUBER® for 8 weeks. The second group received their usual treatment. This randomized control trial has been registered on clinicaltrials.gov under the number NCT04687293. Physical performance and quality of life were evaluated at different time. 3) Results: There was no significant difference between the 2 groups after enrolment. In terms of physical performance, an improvement in SPPB chair stand test (p=0.021) and total SPPB (p=0.003) was observed in the HUBER® group. In terms of quality of life, a higher improvement was observed overall in the HUBER® group (p<0.05 between groups). 4) Conclusion: The HUBER® showed promising results in functional rehabilitation of patients with neurological pathologies, as a complement to classical rehabilitation management by physiotherapy.

In this paper, we derive Von Koch's inequality without using the Riemann Hypothesis. As well known, Von Koch's inequality is equivalent to the Riemann Hypothesis. Namely, we show that the Riemann Hypothesis is true. Furthermore, we show that the upper limit of its can be lowered.

Most existing coal-fired power plants were designed for sustained operation at full load to maximize efficiency, reliability, and revenue, as well as to operate air pollution control devices at design conditions. Depending on plant type and design, these plants can adjust output within a fixed range in response to the plant operating or market conditions. The need for flexibility driven by increased penetration of variable and non-dispatchable power generation such as wind and solar is shifting the traditional mission profile of thermoelectric power plants in three ways: more frequent shutdowns when market or grid conditions warrant, more aggressive load ramp rates (rate of output change), and lower minimum sustainable load, which provides a wider operating range and helps avoid costly plant shutdowns. Recent studies have shown that flexibility of a coal-fired power plant can be improved by energy storage. The objective of this work was to analyze a set of energy storage options and determine their impact on flexibility and economics of a representative coal-fired power plant. The effect of three energy storage systems integrated with a coal power plant on plant flexibility and economics was investigated. The results obtained in this project show that Energy Storage Systems integrated with a thermal power plant improves plant flexibility and participation in the Energy and Ancillary Services markets which improves plant financial performance. The study was funded by the U.S. Department Office of Fossil Energy FE-1 under Award Number DE-FE0031903.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumor microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically “cold” tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data has demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a “cold” tumour microenvironment that is commonly associated with poor response to ICIs, to a “hot” microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression.

The cause of the systematic daily march of barometric pressure in the tropics, notably the late morning and late evening peaks seen almost every day at all locations, was a puzzle that persisted through the nineteenth and much of the twentieth centuries. The efforts to explain the physics of the prominent 12-hour solar tidal variation helped inspire some of the earliest developments in theoretical atmospheric dynamics and ultimately led in the 1960’s to a satisfactory dynamical theory for the atmospheric tides. These important theoretical developments followed the observational discoveries, which date to the late 18th and early 19th centuries, of the surprising character of the barometric daily march and of its resolution into solar and lunar period cycles. These important, if simple, discoveries emerged primarily from the efforts of European scientists to systematically study the environment in remote areas of the globe. The two key figures in initially advancing the scientific community’s understanding of the character of barometric tides were the great German polymath Alexander von Humboldt (1769-1859) and the French naturalist Robert de Lamanon (1752-1787), who each made their discoveries on their most famous and colorful scientific expeditions of their respective careers. This paper examines the history of the early observations of the barometric tide.

We show that the respective oversights in the von Neumann's general theorem against all hidden variable theories and Bell's theorem against their local-realistic counterparts are homologous. Both theorems unjustifiably assume the additivity of expectation values within hidden variable theories to derive their respective conclusions. However, for non-commuting observables, the equivalence of a sum of expectation values and the expectation value of the sum of measurement results, although respected within quantum mechanics, need not hold for hidden variable theories, regardless of specific characteristics such as local realism they may respect. Once this oversight is ameliorated from Bell's argument and local realism is implemented correctly, the bounds on the CHSH correlator work out to be +/-2\/2 instead of +/-2, thereby mitigating the conclusion of Bell's theorem. Consequently, what is ruled out by the Bell-test experiments is not local realism but the additivity of expectation values.

Horizontal transfer of transposons (HTT) is an important source of genomic evolution in eukaryotes. The HTT dynamics is well characterized in eukaryotes including insects however, but there is a huge gap of knowledge about HTT regarding many eukaryotes’ species. In this study we analyzed the events of the HTT between Rhus gall aphids (Hemiptera) and other insects. We analyzed the Mariner-like transposable elements (MLEs) belongs to Rhus gall aphids for the possible HT events. The MLEs have patchy distribution and have high similarity over the entire length of element with insects MLEs from different orders. We selected representative sequences from the Rhus gall MLEs and identified five events of HT between MLEs of Rhus gall aphids and other insects from five different orders. We also found multiple HTT events among the MLEs of insects from the five orders which demonstrate that these Mariner elements have been involved in recurrent HT between these six order of insects. Our current study closed the knowledge gap of HTT and reported the events between Rhus gall aphids and other insects for the first time. We believe that this study about HTT events will help to understand the evolution and spread of transposable elements in the genomes of Rhus gall aphids.

Contextualising the narrative on energy efficiency as the first fuel in the clean energy transition, the energy efficiency first principle (EE1) was introduced in EU energy and climate policy with Energy Union communication in 2015 and made nonbinding with the EU Governance Regulation in 2018. In 2023, the EU legislators made EE1 legally binding to apply in policy, planning and investment decisions exceeding 100 million euros each and 175 million euros in the transport sector across all sectors that affect the energy system. By applying the multiple streams framework, this article analyses the role of policy entrepreneurs in the policy process and politics of making EE1 binding through qualitative text analysis of policy documents, position papers and reports from EU negotiations. The analysis shows how nonprofit and nongovernmental organisations such as the Regulatory Assistance Project, the European Climate Foundation and the Energy Efficiency Financial Institutions Group, as well as the European Commission and the rotating Council Presidency, were critical policy entrepreneurs for coupling the problem, policy and politics streams. The coupling was performed once a policy window was opened by the Paris Agreement on climate change, the entering office of the Ursula von der Leyen European Commission in late 2019, immediately presenting the European Grean Deal as the EU’s climate action plan and green growth strategy, and the energy crisis in Europe following Russia’s second war on Ukraine, leading the Commission to present the REPowerEU Plan and the EU Save Energy Strategy. This paper provides better knowledge of the policy processes and politics related to EE1, contextualising and concretising the concept of energy efficiency as the first fuel into binding law.

Recommender Systems (RecSys) are crucial in managing information overload and enhancing user satisfaction across various digital platforms, including e-commerce and entertainment. Evolving from traditional models to Deep Neural Networks (DNNs) and, more recently, Large Language Models (LLMs), these systems leverage sophisticated algorithms to analyze user behaviors and preferences. LLMs, such as GPT-4, are trained on extensive datasets to comprehend and generate natural language, significantly advancing their ability to deliver personalized recommendations. This tutorial explores the transformative impact of LLMs on RecSys, discussing their development, application in handling complex datasets, and the integration of contextual insights. Real-world examples illustrate how LLMs enhance recommendation accuracy and user experience, highlighting challenges and future directions in the field.

Living walls (LWs) are a climate change adaptation strategy for cities, as they have a cooling effect. Previous studies of the cooling effect of LWs were carried out in different climatic zones. These studies differed in their experimental design, or simulated data via models. Plants’ cooling capacity is explained by shading and transpiration, and depends on physical plant parameters, environmental factors, and system-related influences. A three-year-long trial was carried out between 2017 and 2019 at an experimental garden in Geisenheim, Germany. We chose a textile-based LW system with high water demand and plants from a wet/fresh habitat. We assumed that this would achieve high evaporative cooling. The experimental setup included four experimental walls which were exposed to the north, south, east, and west, respectively. The plant choice was divided into three plant mix variants (Cascade, Ground cover, and Meadow) and a Control with no vegetation. We measured the temperature with sensors and a thermal imaging (IR) camera in different setups. The main results were that the measured vegetation temperature (TV) depends on air temperature (TA), measurement position, plant mix variant, and plant species. We could detect the cooling effect only at a small distance from the LW (microclimatic). Our methodological approaches should be continued in further studies.

. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation (p-Tau) and intracellular p-Tau aggregates known as neurofibrillary tangles (NFTs). This is particularly evident in individuals with Down syndrome (DS), who develop Alzheimer’s disease-like (AD) neuropathology early in life with almost complete penetrance, associated with the development of dementia symptoms in their 40s or 50s. Our previous findings have shown that certain forms of p-Tau are present already in childhood in individuals with DS in neuron-derived exosomes, suggesting an early phosphorylation profile in this population that could influence the development of AD pathology. Misfolded p-Tau isoforms are known to be seeding competent and may be responsible for spreading AD pathology in different regions of the brain. This review is focused on the accumulation of p-Tau in the brain of individuals with DS and potential consequences for brain function.

Legionella bacteria can proliferate in poorly maintained water systems, posing risks to users. All Legionella species are potentially pathogenic but Legionella pneumophila (L. pneumophila) is usually the primary focus of testing. However, Legionella anisa (L. anisa) also colonises water distribution systems, is frequently found with L. pneumophila and could be a good indicator for increased risk of nosocomial infection. Anonymized data from three commercial Legionella testing laboratories afforded analysis of 565,750 water samples. Data covered July 2019 to August 2021, including the COVID-19 pandemic. Results confirmed L. anisa commonly colonises water distribution systems, being the most frequently identified non-L. pneumophila species. Proportions of L. anisa and L. pneumophila generally remained similar but increases in L. pneumophila during COVID-19 lockdown suggests static water supplies might favour its growth. Disinfection of hospital water systems was effective but re-colonization did occur, appearing to favour L. pneumophila, although L. anisa colony numbers also increased as a proportion of the total. While L. pneumophila remains the main species of concern as a risk to human health, L. anisa’s role should not be under-estimated, either as a potential infection risk or as an indicator of the need to intervene to control Legionella colonization of water supplies.

There is a growing consensus that to effectively adapt to climate change, cities need user-friendly tools and reliable high-resolution biophysical and socio-economic data for analysis, mapping, modeling, and visualization. This study examines availability of various types of information used in climate adaptation plans of 40 municipalities with population less than 300,000 people in the United and in France, probing into the choice and usage of relevant information by small municipalities. We argue that non-climatic spatial data, such as population demographic and socio-economic patterns, urban infrastructure, and environmental data must be integrated with climate tools and datasets to inform effective vulnerability assessment and equitable climate adaptation planning goals. Climate adaptation plans frequently fail to address the existing structural inequalities and environmental injustices in urban infrastructure and land use. Adaptation methodological approaches should be reassessed in the context of much needed societal transformation. Lessons learned from our studies offer valuable insights for potential development of the national and state-level climate adaptation information services for cities.

Artificial intelligence (AI) systems are poised to become deeply integrated into society. If developed responsibly, AI has potential to benefit humanity immensely. However, it also poses a range of risks, including risks of catastrophic accidents. It is crucial that we develop oversight mechanisms that prevent harm. This article outlines a framework for evaluating and auditing AI to provide assurance of responsible development and deployment, focusing on catastrophic risks. We argue that responsible AI development requires comprehensive auditing that is proportional to AI systems’ capabilities and available affordances. This framework offers recommendations toward that goal and may be useful in the design of AI auditing and governance regimes.

The voice contains elementary social communication cues, conveying speech, as well as paralinguistic information pertaining to the emotional state and the identity of the speaker. In contrast to vocal-speech and vocal-emotion processing, voice-identity processing has been less explored. This seems surprising, given the day-to-day significance of person recognition by voice. A valuable approach to unravel how voice-identity processing is accomplished is to investigate people who have a selective deficit in recognising voices. Such a deficit has been termed phonagnosia. In the present chapter, we provide a systematic overview of studies on phonagnosia and how they relate to current neurocognitive models of person recognition. We review studies that have characterised people who suffer from phonagnosia following brain damage (i.e. acquired phonagnosia) and also studies, which have examined phonagnosia cases without apparent brain lesion (i.e. developmental phonagnosia). Based on the reviewed literature, we emphasise the need for a careful behavioural characterisation of phonagnosia cases by taking into consideration the multistage nature of voice-identity processing and the resulting behavioural phonagnosia subtypes.

In this work, we propose a transition wave equation from quantum to classical regime in the framework of the von Neumann formalism for ensembles and then obtain an equivalent scaled equation. This leads us to develop a scaled statistical theory following the well-known Wigner-Moyal approach of quantum mechanics. This scaled nonequilibrium statistical mechanics has in it all the ingredients of the classical and quantum theory described in terms of a continuous parameter displaying all the dynamical regimes in-between the two extreme cases. Finally, a simple application of our scaled formalism consisting of reflection from a mirror by computing various quantities including probability density plots, scaled trajectories and arrival times are analyzed.

Our study reviews the significance of archaeological parks in the tourism sector, with a specific focus on how digital presence and visitor feedback impact their cultural and touristic appeal. Utilizing statistical analyses such as regression and cluster analysis on data sourced from both Hungarian and Western European parks, the research scrutinizes TripAdvisor and Google ratings, alongside the volume of photographs and reviews. The findings highlight a modest correlation between digital visibility and overall visitor ratings, underscoring the complex relationship between online engagement and the quality of visitor experience. Notably, the cluster analysis identified two distinct groups, signifying diverse levels of visitor engagement and digital visibility across the parks. The conclusions drawn advocate for a comprehensive strategy to enhance visitor experiences, emphasizing the integration of digital engagement with the promotion of the parks cultural and historical values. By exploring the influence of digital presence on the appeal of archaeological parks, our study sheds light on the evolving interface between urban studies and digital heritage, highlighting how digital tools and online platforms are becoming increasingly integral in shaping the perceptions and experiences of urban cultural sites.

Fragment-based drug discovery (FBDD) has become a major strategy to derive novel lead candidates for various therapeutic targets, as it promises efficient exploration of chemical space by employing fragment-sized (MW < 300) compounds. One of the first challenges in implementing a FBDD approach is the design of a fragment library, and more specifically, the choice of its size and individual members. A diverse set of fragments is required to maximise the chances of discovering novel hit compounds. However, the exact diversity of a certain collection of fragments remains underdefined, which hinders direct comparisons among different selections of fragments. Based on structural fingerprints, we herein introduced quantitative metrics for the structural diversity of fragment libraries. Structures of commercially available fragments were retrieved from the ZINC database, from which libraries with sizes ranging from 100 to 100,000 compounds were selected. The selected libraries were evaluated and compared quantitatively, resulting in interesting size-diversity relationships. Our results demonstrated that while library size does matter for its diversity, there exists an optimal size for structural diversity. It is also suggested that such quantitative measures can guide the design of diverse fragment libraries under different circumstances.

The increasing complexity of vehicular traffic and the prevalence of accidents, particularly rear-end collisions, necessitate enhancements in automotive safety technologies. Adilights, an innovative automotive lighting system, addresses this need by introducing a dynamic visual communication method between vehicles. This system features a novel design that employs variable-intensity brake lights configured in an upside-down "U" shape to indicate braking severity. The intensity and pattern of the lights change in response to the pressure applied to the brake pedal, providing clear and immediate feedback to following drivers. This design not only improves the perceptibility of braking signals, particularly in dense traffic and poor visibility conditions but also aims to reduce the frequency of rear-end collisions significantly. The paper details the development and testing of Adilights, discusses its integration with current vehicular systems, and evaluates its effectiveness through simulated scenarios. The introduction of Adilights marks a step forward in the use of adaptive lighting systems for enhanced vehicular communication and road safety.\cite{Lee2007RearEnd}

Global stress is widespread in todays post-pandemic world of political and economic uncertainty. Vibroacoustic technology is a vibrotactile intervention with multiple uses, and its impact on stress lacks interpretation. This research assessed if the vibroacoustic technology of a Vibroacoustic Sound Massage (VSM) can reduce psychological, physiological and cognitive stress. The Perceived Stress Scale (PSS-10), and electrocardiogram (ECG) and electroencephalogram (EEG) biosignals were used to quantify results. Participants were divided into Low Stress and High Stress groups. ECG results show VSM increased parasympathetic activity for all participants, with the Low Stress group more effected. EEG results indicate increased concentration (TBR), reduced arousal and increased relaxation (BAR), and non-significant effects on participant well-being (FAA), though variability in this metric was homogenised after VSM. Together, these results validate VSM as an effective support tool for stress management and further research is required.

We present a method to study the interannual variability of the annual cycle. The method consists of first determining the amplitude and phase of segments of 12 monthly means at all spatial points, resulting in one complex number per grid point and per year. The complex fields, once per year, are then subject to a complex EOF (CEOF) analysis. We consider as an example the barotropic stream function in the South China Sea as simulated with an ocean general circulation model across 6 decades of years, driven my realistic (NCEP) weather forcing. We find 3 to 4 to “significant” CEOFs, which account for about 53 to 62% of variance. These CEOFs go with large-scale patterns. Their time coefficients are mostly stationary, but point to some inhomogeneities related to instationarities in the forcing. In particular, the simulation since 1950-1958 deviates from the remainder of the simulation. The first CEOF describes variations in the center of the South China Sea. Its principal component describes a systematic, albeit noisy shift by almost 180o from 1960 to about the year 2000. When overlaid the long-term mean annual mean, the overall change consists of an amplification of the annual cycle in the 1960s and 1990s, whereas In the 1970s, the amplitude was reduced. Phase shifts in the anomaly (given by the CEOFs) have a small effect, because of the dominance of the mean annual cycle. These variations are not related to ENSO variability but may origin in variations of the Southeast monsoon. The second EOF represents strong changes, both in terms of intensity and phase, in the Luzon strait.

The southeast of Spain is one of the most arid and desertification-prone areas in continental Europe, with climate change contributing to this situation. Climatic conditions affect the availability of water in the plant structures of wild species, facilitating the onset and/or spread of forest fires and increasing aridity. The Region of Murcia, in southeastern Spain, has small forest stands of gall oak (Quercus faginea) with relict value. It is of interest to investigate the situation of these stands, allowing us to know about their distribution and their evolution in the face of climate change. For this purpose, previous dasometric, available from a specific stand, studies are considered to be contrasted with current data, individual trees were geolocated, and distribution maps of contrasting environmental conditions were created. In general, gall oak has been observed to be distributed up to 1200 m altitude, especially in shady areas and embedded valleys and north-northeast orientations. Importantly, there was a positive evolution of the vegetative development, with increments in the number of trees during the study period, despite some negative affections in specific areas due to climate change.

When limited area models of the hydrodynamics of the atmosphere and of the ocean are 1 run over an extended time, variability unrelated to external "drivers" emerge - this variability is 2 colloquially named "hydrodynamical noise" or just "noise". This article summarises what we have 3 learned in the past few years about the properties of such noise, and the implications for numerical 4 experimentation and analysis. The presence of this noise can be identified easily in ensembles of 5 numerical simulations, and it turns out that the intensity of the noise is closely linked to the scale- 6 dependent "memory". At the system level, this "memory" term as given by Hasselmann’s Stochastic 7 Climate model plays a key role. In the case of marginal seas, the process of baroclinic instability 8 modulated by tides and the formation of seasonal thermoclines are significant aspects. Some more 9 general aspects are discussed, such as the applicability of the Stochastic Climate model to systems 10 outside of atmospheric and oceanic dynamics, the irreversibility of tipping points and the challenges 11 of detecting changes beyond a noise level and of the attribution of causes of change.

We introduce the notion of p-adic magic contraction on p-adic Hilbert space. We derive p-adic Halmos dilation, p-adic Egervary N-dilation, p-adic von Neumann inequality and p-adic Sz.-Nagy dilation for p-adic magic contraction.

Complex problem-solving (CPS) tasks have become an increasingly popular tool for understand-ing and assessing cognitive ability. These tasks have been repeatedly shown to be predictors of academic and workplace success above and beyond traditional measures of general intelligence and fluid intelligence. To date, there has been little exploration of the underlying mechanisms that drive this additional predictive utility. In this study, we examined the role of a variety of non-cognitive personality and investment traits that could drive performance on CPS tasks. Adult participants (n = 152) were recruited via M-Turk and completed a battery of personality and in-vestment trait measures, a measure of general mental ability, and a 61-trial microworlds-style CPS task. Generalised linear mixed-effects models revealed a wide variety of personality and in-vestment traits influenced task performance above and beyond general mental ability. Specifical-ly, two clusters of traits emerged as important determinants of performance: one cluster that in-fluenced the capacity to deal with the introduction of system randomness (Conscientiousness and Extraversion) and one cluster that influenced the capacity to deal with the introduction of system delays (NFC, Learning Goal Orientation, and Intellect). These findings suggest that CPS tasks do capture more than just general mental ability and may be good predictors of academic and workplace success because they tap into both cognitive ability and the motivation and willingness to engage in cognitive exploration and mental effort.

1. Background Septic shock is a rare and serious infectious disease. Patients surviving the early phase are at high risk of multiple amputations of limbs. They are potential sources of serious disability. 2. Methods The objective was to describe the functional prognosis and quality of life of the four-limb amputee patients following septic shock. This is a descriptive, retrospective and mono-centric study. The patients included between 2010 and 2019 had septic shock after 18 years, responsible for amputation of the four limbs. We studied the mean age of septic shock, the causative organisms, the infectious door enter, the different levels of amputation, the fitting process, the resumption of walking, the Functional Independence Measure (FIM) and the SF-12 Quality of Life Questionnaire. 3. Results We suceed to include 15 patients.. 53.3% women and 46.7% men with an average age of 46.1 years. 80% presented bilateral trans-tibial amputations, all were able to return walking even over short distances, within an average of 8.4 months. 40% did not require a technical walking aid, 33.3% had no walking perimeter limitation. 47% had a higher mental and social quality of life score than the general population. The younger the patients, the better their physical quality of life. After two years of follow-up, the younger the patients, the better their functional autonomy. Patients with better functional autonomy had a better physical quality of life. 4. Conclusion The number of amputations due to spetic shock is likely to increase in the years to come throughout the world. Our study prove that quadri-amputee patient can regain a fully acceptable functional and quality of life being monitored in a specialized health center with multidisciplinary health professional to help him.

Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise“ or “personalized“ enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.

The transmission and analysis of data is one of the challenges of the 21st century. In the field of environmental measurement technology, existing broadband and wireless technologies have not been able to transmit data reliably and cost-effectively over long distances and in hard-to-reach places. LoRaWAN, an IoT technology, could be an energy-efficient, cost-effective and secure alternative as a narrowband technology in combination with battery-powered sensors and thus make an important contribution to the intelligent, largely wireless networking of objects, plants and machines (IoT), for example in the municipal sector. In addition to ecological and economic benefits, the quality of life in modern, intelligently networked cities can be enhanced by real time data acquisition. However, the prerequisite is that the quality of the data acquired via this method is sufficiently good. This paper therefore addresses the question of the quality of particulate matter data collected by low-cost sensors. To determine this, an SDS011 particulate matter sensor from Nova Fitness was ported to LoRaWAN. The sensor was installed next to a governmental measurement station. In a test that lasted five weeks, data from the SDS011 sensor were compared with those from the governmental station. Differences were identified and a correction approach was developed and applied. The efficiency of the approach was verified. Based on the results, it can be seen that the use of the low cost sensors has weaknesses. Problems can only be partially reduced. Nevertheless, the use of the low-cost sensors can be helpful for a flexible and cost effective collection of environmental data.

We review the state of dynamical downscaling with scale-constrained regional and global models. The methodology, in particular spectral nudging, has become a routine and well-researched tool for hindcasting climatologies of sub-synoptic atmospheric disturbances in coastal regions. At present, the spectrum of applications is expanding to other phenomena, but also to ocean dynamics and to extended forecasting. Also new diagnostic challenges are appearing such as spatial characteristics of small-scale phenomena such as Low Level Jets.

HIV-1 assembly is a complex mechanism taking place at the plasma membrane of the host cell. It requires nice spatial and temporal coordination to end up with a full immature virus. Researchers have extensively studied HIV-1 assembly molecular mechanism during the past decades, in order to dissect the respective roles of viral proteins, viral genome and host cell factors. Nevertheless, the time course of the process has been observed in living cells only a decade ago. The very recent revolution of optical microscopy, combining high speed and high spatial resolution now permit to study assemblies and their consequences at the single molecule level within (living) cells. In this review, after a short description of these new approaches, we will show how HIV-1 assembly in cells has been revisited using these advanced super resolution microscopy techniques and how much it could make a bridge in studying assembly from the single molecule to the host cell.

Residential coal combustion is one of the most significant sources of carbonaceous aerosols in the Highveld region of South Africa, significantly affecting the local and regional climate. In this study, we investigated single coal-burning particles emitted when using different fire-ignition techniques (top-lit up-draft vs bottom-lit up-draft) and air ventilation rates (defined by the number of air holes above and below the fire grate) in selected informal braziers. Aerosol samples were collected on nucleopore filters at the Sustainable Energy Technology and Research Centre Laboratory, University of Johannesburg. Individual particles (~700) were investigated using a scanning electron microscope equipped with energy-dispersive X-ray spectroscopy (EDS). Two distinct forms of spherical organic particles (SOPs) were identified, one less oxidized than the other. The particles were further classified into "electronically" dark and bright. EDS analysis showed that 70% of the dark spherical organic particles had higher (~60%) relative oxygen content than in the bright SOPs. We quantified the morphology of spherical organic particles and classified them into four categories: ~50% are bare single particles; ~35% particles are aggregated and form diffusion accretion chains; 10% have inclusions, and 5% are deformed due to impaction on filter material during sampling. We conclude that there are two distinct kinds of coal burning spherical organic particles and that dark SOPs are less volatile than bright SOPs. We also show that these spherical organic particles are similar in nature and characteristics to tar balls observed in biomass combustion and that they have the potential to absorb sunlight thereby affecting the earth’s radiative budget and climate. This study provides insights into the mixing states, morphology, and possible formation mechanisms of these organic particles from residential coal combustion in informal stoves.

Let $m$ and $n$ be the fixed positive integers. Suppose $\mathcal{A}$ is a von Neuman algebra with no central summands of type $I_{1}$ and $L_{m}$ be a Lie type higher derivation i.e., an additive (linear) map $L_{m} :\mathcal{A}\to \mathcal{A}$ such that \begin{equation}\label{def2} \[L_{m}(p_{n}(\mathfrak{S}_{1},\mathfrak{S}_{2},\cdots,\mathfrak{S}_{n}))=\sum_{l_1+l_2+\cdots+l_n=m}p_{n}\big(L_{l_1}(\mathfrak{S}_{1}),L_{l_2}(\mathfrak{S}_{2}),\cdots,L_{l_n}(\mathfrak{S}_{n})\big)\] %L_{m}(p_{n}(\mathfrak{S}_{1},\mathfrak{S}_{2},\cdots,\mathfrak{S}_{n}))=\sum_{l_1+l_2+\cdots+l_n=m}p_{n}\big(L_{l_1}(\mathfrak{S}_{1}),L_{l_2}(\mathfrak{S}_{2}),\cdots,L_{l_n}(\mathfrak{S}_{n})\big)\nonumber \end{equation} for all $\mathfrak{S}_{1},\mathfrak{S}_{2},\cdots,\mathfrak{S}_{n}\in \mathcal{A}$. In the present paper, we study Lie type higher derivations on von Neuman algebras and prove that every additive Lie type higher derivation on $\mathcal{A}$ has a standard form at zero product as well as at projection product. Further, we discuss some more related results.

This scoping study aims to explore the relationships between urban green spaces (UGSs) and cancer. We followed the PRISMA extension for scoping reviews (protocol published in 2018). Eligibility criteria for papers were: 1) to be concerned with UGSs, 2) reporting effects of UGSs on cancer-related outcomes including direct or indirect measures, 3) reporting randomized controlled trials, prospective cohort studies, case studies, observational studies, non-comparative studies, 4) in English or French. The search covered primary studies in the published and unpublished (grey) literatures searching by hand and electronic databases (MEDLINE, Green File, CINAHL and ScienceDirect). Among 1703 records screened by two reviewers independently, 29 were included for qualitative synthesis. We classify the cancers concerned and the effects reported i.e. protective effect, risk or without association. The most investigated cancers are bladder, breast and lung cancer. Our study also identified contributing factors and their mediating effects between UGSs and cancer. Results highlight the wide variety of possible mediating factors between the use of green spaces and cancer occurrence, remission and/or prevention. Knowledge gaps and future research perspectives should be oriented to qualitative research on protective factors, the role of mental health in recovering from cancer and health inequalities.

GCTs are developmental tumors and likely to reflect ontogenetic and teratogenetic determinants. The objective was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were used. According to Teilum's holistic concept malignant and benign teratomas were registered. We used a case control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher’s exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7-2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2-88.6). We additionally found 17 isolated cases of eGCT with a wide range of syndromes, however not significantly associated following Bonferroni correction. All these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies.

Retinitis pigmentosa (RP) is a frequent cause of blindness among the working population in industrial countries, due to the inheritable death of photoreceptors. Though a gene therapy was recently approved for mutations in the RPE65 gene, there is generally no effective treatment presently. Previously, abnormally high-level cGMP and overactivation of its dependent protein kinase (PKG) have been suggested as causative for the fatal effects on photoreceptors, making it meaningful to explore the cGMP-PKG downstream signaling for more pathological insights and novel therapeutic target development purposes. Here we manipulated the cGMP-PKG system in degenerating retinas from the rd1 mouse model pharmacologically via adding a PKG inhibitory cGMP-analogue to organotypic retinal explant cultures. A combination of phosphorylated peptides enrichment and mass spectrometry was then applied to study the cGMP-PKG-dependent phosphoproteomics. We identified a host of novel potential cGMP-PKG downstream substrates and related kinases using this approach, and selected the RAF1 protein, which may act as both a substrate and a kinase, for further validation. We showed that the RAS/RAF1/MAPK/ERK pathway may be involved in retinal degeneration in a yet unclarified mechanism, thus deserving further investigation in the future.

Background: Infectious disease is a major challenge in aquaculture and poses a constraint for development of farming of new species. In 2017, Siberian sturgeon (Acipenser baerii) juveniles were imported from Italy to a Swedish farm. Due to stressful conditions, 30% died during transport and in the first days after arrival. Ten days after arrival, mortalities started to occur again. Within two months, only 5% of the juveniles were still alive. Methods: Diseased fish were transported live to the National Veterinary Institute (SVA) for necropsy and further analysis. Pathological and histopathological investigation was conducted. Virology was performed on gills and internal organs by cell culture isolation and specific PCR protocols. Results: The juveniles displayed neurological signs such as lethargy, inability to maintain upright position and erratic swimming. Body condition was low. Gills were pale. One fish had petechial hemorrhage on the abdomen and the snout. The ventricles were air-filled with, but swim bladders were deflated. One specimen had intestinal hemorrhage. Viral cell cultures were negative, but PCR of gills and internal organs detected the presence of Acipenser Iridovirus European (AcIV-E). Conclusions: AcIV-E was associated with disease and high mortality in the sturgeon juveniles. Stress probably aggravated the course of the infection.

Trichoderma sp. is a fungus in the genus Trichoderma, ubiquitous in soils, on plant roots and in decaying plant residues. Due to its competitiveness and mycoparasitic potential against other microorganisms, particular strains of Trichoderma sp. are used in agriculture as biocontrol agents against plant pathogens. However, Trichoderma afroharzianum. has been recently reported as a pathogen causing ear rot disease on maize in Germany, France and Italy leading to massive infections on maize cobs. This raised the question, whether and to what extend Trichoderma can infect other cereal crops than maize and cause disease symptoms and yield losses. To address this question, two varieties of wheat, barley and sorghum millet were grown in the greenhouse and artificially inoculated with T. afroharzianum by both spray and point inoculation at the time of flowering. Disease severity was scored weekly and thousand-kernel weight and colonization rate were determined after harvest. As early as 14 days after inoculation, the first visual symptoms appeared on wheat and barley as tan or brown discoloration of the base of a floret within the spikelets. After spray inoculation, clear discolorations of the entire ear were seen, while point inoculation only showed symptoms at the injection site and above. No visible symptoms were observed on sorghum millet. The colonization rate on wheat and barley grains was significantly increased compared to the control while thousand kernel weights (TKW) were significantly reduced. No differences in colonization rate and TKW compared to the control were observed in sorghum. This is the first report of Trichoderma afroharzianum infecting wheat and barley, causing diseases symptoms and significantly reducing thousand-kernel weights.

The new barrier mode in Apache Spark allows embedding distributed deep learning training as a Spark stage to simplify the distributed training workflow. In Spark, a task in a stage doesn’t depend on any other tasks in the same stage, and hence it can be scheduled independently. However, several algorithms require more sophisticated inter-task communications, similar to the MPI paradigm. By combining distributed message passing (using asynchronous network IO), OpenJDK’s new auto-vectorization and Spark’s barrier execution mode, we can add non-map/reduce based algorithms, such as Cannon’s distributed matrix multiplication to Spark. We document an efficient distributed matrix multiplication using Cannon’s algorithm, which improves significantly on the performance of the existing MLlib implementation. Used within a barrier task, the algorithm described herein results in an up to 24% performance increase on a 10,000x10,000 square matrix with a significantly lower memory footprint. Applications of efficient matrix multiplication include, among others, accelerating the training and implementation of deep convolutional neural network based workloads, and thus such efficient algorithms can play a ground-breaking role in faster, more efficient execution of even the most complicated machine learning tasks

The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.

Adventurous play, defined as exciting, thrilling play where children are able to take age-appropriate risks has been associated with a wide range of positive outcomes. Despite this, it remains unclear what factors might aid or hinder schools in offering adventurous play opportu-nities. The purpose of this systematic review is to synthesise findings from qualitative studies on the perceived barriers and facilitators of adventurous play in schools. A total of nine studies were included in the final synthesis. The review used two synthesis strategies: a meta-aggregative syn-thesis and narrative synthesis. Findings were similar across the two syntheses, highlighting that key barriers and facilitators were: adults’ perceptions of children; adults’ attitudes and beliefs about adventurous play and concerns pertaining to health; and, safety and concerns about legis-lation. Based on the findings of the review, recommendations for policy and practice as provided to support adventurous play in schools.

Background: Granular cell tumor is a benign neurogenic tumor of the subcutaneous and submucosal area. The tongue is the most affected site of the oral cavity. The clinical presentation is non-specific and manifests as a submucosal nodule or mass. Because of its non-specific presentation, a definitive diagnosis an only be established after a histopathological examination and an immunohistochemical study to search for a neurogenic origin. Methods: We report the case of a 48-year-old man who was referred for the management of a nodular lesion on the tip of his tongue that had increased in size over the previous three months. Results: A complete surgical excision was performed for the histopathological exam, and an immunohistochemical study confirmed a strong expression of S100 and CD68. A diagnosis of granular cell tumor was confirmed. There was no recurrence et three years follow-up. Conclusion: the GCT is a rare tumor of nervous origin of the oral mucosa, it is non-specific in expression, with a good prognosis after complete excision. the histological and immunohistochemical diagnosis of the lesion is essential for the diagnosis.

Phenol is added to acetophenone (methyl phenyl ketone) and to six of its halogenated derivatives in a supersonic jet expansion to determine the hydrogen bonding preference of the cold and isolated 1:1 complexes by linear infrared spectroscopy. Halogenation is found to have a pronounced effect on the docking site in this intermolecular ketone balance experiment. The spectra unambiguously decide between competing variants of phenyl group stacking due to their differences in hydrogen bond strength. Structures where the phenyl group interaction strongly distorts the hydrogen bond are more difficult to quantify in the experiment. For unsubstituted acetophenone, phenol clearly prefers the methyl side despite a predicted sub-kJ/mol advantage which is nearly independent of zero point vibrational energy, turning this complex into a challenging benchmark system for electronic structure methods which include long range dispersion interactions in some way.

Artificial Intelligence based on Deep Learning is opening new horizons in Biomedical research and promises to revolutionize the Microscopy field. Slowly, it now transitions from the hands of experts in Computer Sciences to researchers in Cell Biology. Here, we introduce recent developments in Deep Learning applied to Microscopy, in a manner accessible to non-experts. We overview its concepts, capabilities and limitations, presenting applications in image segmentation, classification and restoration. We discuss how Deep Learning shows an outstanding potential to push the limits of Microscopy, enhancing resolution, signal and information content in acquired data. Its pitfalls are carefully discussed, as well as the future directions expected in this field.

Background: Plasma levels of von Willebrand factor (VWF) are significantly elevated in patients with COVID-19. However, the dynamic changes and prognostic value of this biomarker in hospitalized patients with COVID-19 are not determined. Methods: 124 patients infected with SARS-CoV2 were prospectively recruited for the study. Serial blood samples were obtained at the time of admission (D1), 3-4 days following standard of care treatments (D2), and 1-2 days prior to discharge or death (D3). Plasma VWF antigen, ADAMTS13 antigen and activity, as well as the ratio of VWF/ADAMTS13 were determined, followed by statistical analyses. Results:While admission plasma levels of VWF in COVID-19 patients were significantly elevated, no statistical significance was detected among patients of different disease severity. Plasma ADAMTS13 activity, but not its antigen levels, were significantly lower in patients with severe or critical COVID-19 compared with other groups. Interestingly, the ratios of plasma VWF antigen to ADAMTS13 antigen were significantly higher in patients with severe or critical COVID-19 than in those with mild to moderate disease. More importantly, plasma levels of VWF and VWF/ADAMTS13 ratios were persistently elevated in patients with COVID-19 during hospitalization. Kaplan-Meier and Cox proportional hazard regression analysis revealed that an increased plasma VWF or ratio of VWF/ADAMTS13 at D2 and D3 associated with an increased mortality rate. Conclusions: Persistent endotheliopathy, marked by an elevated level of plasma VWF or an increased VWF/ADAMTS13 ratio, is present in all hospitalized patients following SARS-CoV2 infection and strongly associated with mortality.

This study addresses the challenge of treating skin cancer effectively, especially in visible areas like the face, where traditional methods may be undesirable. Current options, including surgery and radiation therapy, have limitations such as complexity, expense, and imprecise dose delivery. The proposed solution involves additively manufacturing personalized patches using diagnostic imaging data, offering a targeted and controlled dose of beta-emitting isotopes like Y-90. The patches, tailored to the tumor's shape and depth, aim to minimize damage to healthy tissues and structures. Through 3D printing technology we demonstrated the feasibility of creating individualized applicators filled with radioisotopes, that have the potential to deliver therapeutic doses while ensuring patient comfort and affordability. This innovative approach, based on radiation delivery simulations, offers a promising future alternative to conventional radiation therapy methods. Clinical trials are required to validate its efficacy and safety, but the potential for reduced radiation exposure and enhanced treatment precision positions this personalized and targeted therapy as a valuable advancement in skin cancer treatment.

Elevated carbon dioxide (eCO₂) stimulates wheat grain yield, but simultaneously reduces protein (N) concentration. Also other essential nutrients are subject to change. This study is a comprehensive synthesis of wheat experiments with eCO₂, estimating effects on N, minerals (B, Ca, Cd, Fe, K, Mg, Mn, Na, P, S, Zn), and starch. Analysis was made by i) deriving response functions for the relative effect on element concentration in relation to CO₂ concentration, ii) meta-analysis to test the magnitude and significance of observed effects, and iii) relating CO₂ effects on minerals to effects on N and grain yield. Responses range from zero to strong negative effects of eCO₂ on mineral concentration, with largest reductions for the nutritionally important elements N, Fe, S, Zn and Mg. Together with the positive but small and non-significant effect on starch concentration, the large variation in effects suggests that CO₂-induced responses cannot be explained by a simple dilution model. To explain the observed pattern, uptake and transport mechanisms may have to be considered, along with the link of different elements to N uptake. Our study shows that eCO₂ has a significant effect on wheat grain stoichiometry, with implications for human nutrition in a world of rising CO₂.

The influence of distant London dispersion forces on the docking preference of alcohols of different size between the two lone electron pairs of the carbonyl group in pinacolone is explored by infrared spectroscopy of the OH stretching fundamental in supersonic jet expansions of 1:1 solvate complexes. Experimentally, no pronounced tendency of the alcohol to switch from the methyl to the bulkier tert-butyl side with increasing size is found. In all cases, methyl docking dominates by at least a factor of two, whereas DFT-optimized structures suggest a very close balance for the larger alcohols, once corrected by CCSD(T) relative electronic energies. Together with inconsistencies when switching from a C4 to a C5 alcohol, this points at deficiencies of the investigated B3LYP and in particular TPSS functionals even after dispersion correction, which cannot be blamed on zero point energy effects. The search for density functionals which describe the harmonic frequency shift, the structural change and the energy difference between the docking isomers of larger alcohols to unsymmetric ketones in a satisfactory way is open.

Eurytoma erythrinae Gates & Delvare (Hymenoptera: Eurytomidae), is an important biological control agent of the erythrina gall wasp (EGW), Quadrastichus erythrinae Kim (Hymenoptera: Eulophidae), an invasive species native likely originating in eastern Africa, that is a threat to Erythrina trees in Hawaii and worldwide. Thousands of Erythrina trees in Hawaii succumbed to EGW since 2005 and died within few years of infestation. The endemic wiliwili tree, Erythrina sandwicensis, an important component of Hawaii’s dry forests, and one of few deciduous native trees were severely impacted by this wasp. Early during the invasion by EGW it became evident that the endemic species may be driven to extinction, and exploration programs for natural enemies of the EGW started in December 2005. East Africa was selected as the start point for natural enemy exploration owing to high native Erythina species richness. Several gall formers were found in Tanzania and a putative color variant type of Q. erythrinae was detected in association with three ectoparasitoids. During January 2006, the dominant parasitoid of this gall former was introduced to Hawaii and described as the new species, E. erythrinae. It was found in Ghana, and South Africa attacking other gall wasp species on Erythrina. Eurytoma erythrinae was a voracious ectoparasitoid feeding as a predator on 1 – 5 adjacent EGW immatures to complete its development. Host specificity studies that included seven non-target gall-forming species showed no evidence of attraction or parasitism by this parasitoid. Mean ± SEM longevity of host deprived females (40.4 ± 2.2 days) was significantly higher than males (20.5 ± 1.1 days). Host feeding enhanced longevity of ovipositing female (51.3 ± 1.5 days). Female’s peak fecundity (105 – 239 offspring /female), host feeding biology, short life cycle (18.4 ± 0.1 days), and synchronization with the host, were additional desirable attributes of E. erythrinae. The parasitoid was approved for field release in Hawaii in November 2008. A total of 3998 wasps were distributed on six Hawaiian Islands, with establishment in less than a year. Impacts on high density infestations of EGW were sufficient to prevent tree deaths. Limited rates of parasitism on low density galled leaves, flowers, and seedpods necessitated the consideration for releasing a second parasitoid, Aprostocetus nitens (Hymenoptera: Eulophidae). We report on the reproductive characteristics, and host specificity of E. erythinae that could be of importance for classical biocontrol programs in areas with EGW problem.

Background: Access to rehabilitation is crucial for the realization of the right to health and a proper concern of global health. Yet, reliable information to guide rehabilitation service planning is unavailable in many countries in part due to the lack of appropriate indicators. To ensure universal health coverage and meet the central imperative of “leaving no one behind” countries must be able to assess key aspects of rehabilitation policy and provision and monitor how they have discharged their human rights responsibilities towards those most disadvantaged, including people with disability. This article describes the process of developing an expert guided indicator framework to assess governments’ efforts and progress in strengthening rehabilitation in line with the Convention on the Rights of Persons with Disabilities. Methods: A systems methodology - concept mapping - was used to capture, aggregate and confirm the knowledge of diverse stakeholders on measures thought to be useful for monitoring the implementation of the Convention with respect to health related rehabilitation. 56 individuals generated a list of 107 indicators through online brainstorming which were subsequently sorted by 37 experts from the original panel into non overlapping categories. 41 participants rated the indicators for importance and feasibility. Multivariate statistical techniques where used to explore patterns and themes in the data and create the indicators’ organizing framework which was verified and interpreted by participants. Results: A concept map of 11 clusters of indicators emerged from the analysis grouped into three broader themes: Governance and Leadership (3 clusters); Service Delivery, Financing and Oversight (6 clusters); and Human Resources (2 clusters). The RESYST was comprehensive and well aligned with the Convention. On average, there was a moderately positive correlation between importance and feasibility of the indicators (r=.58) with experts prioritizing the indicators contained in the clusters of the Governance and Leadership domain. Two of the most important indicators arose from the Service Delivery, Financing and Oversight domain and reflect the need to monitor unmet needs and barriers in access to rehabilitation. In total, 59 indicators achieved above average score for importance and comprised the two–tiered priority set of indicators. Conclusion: Concept mapping was successful in generating a shared model that enables a system’s view of the most critical legal, policy and programmatic factors that must be addressed when assessing country efforts to reform, upscale and improve rehabilitation services. The RESYST provides a data driven basis for the development of standardized data collection tools to facilitate comparative analysis of rehabilitation systems.

The adoption of an entrepreneurial mindset within the lenses of green entrepreneurship contributes to negotiating a transdisciplinary and multidisciplinary approach by intertwining industrial psychology and industrial engineering through [system dynamics] which forms part of the paper's focus. The methodology used in this study is a system dynamics methodology using data readily available online with a focus on quantitative methodology. This study's dynamic variable and the causal loop are formulated using the Euler mathematical equation with support from the Vensim modelling software (academic purposes license). Results and variables simulated in the current study are entrepreneurial mindsets [through subfield of education, values, intentions and gender representation] contribution and the conclusion is explained towards the end of the paper.

Functional somatic disorders (FSD) characterized by persistent and disabling physical symptoms are common in adolescents. Diagnostic uncertainty and insufficient illness explanations are proposed perpetuating factors that may constitute barriers for treatment engagement. This study evaluates the impact of manualized assessment and psychoeducation on diagnostic certainty and various clinical outcomes in adolescents with multi-system FSD. Ninety-one adolescents (15-19 years) included in a randomized trial testing group-based therapy (AHEAD) received systematic assessment (4 hrs.) and a subsequent psychiatric consultation (1.5 hrs.). Clinical outcomes included self-reported physical health, symptom severity, illness perception, illness related behavior, and psychological flexibility assessed before and approximately two months after assessment, prior to specialized treatment. Data were analyzed using t-tests. Immediately following assessment 71 (80.7%) adolescents out of 88 reported a higher diagnostic certainty and 74 (84.1%) reported that attending assessment gave them positive expectations for future treatment. A clinically relevant improvement of physical health was not observed at two months but considerable reductions were seen on symptom severity, illness worry, negative illness perceptions, limiting illness behavior and psychological inflexibility. The results underpin the importance of systematic assessment and psychoeducation which may be effective in their own right in specialized treatment of adolescents with severe FSD.

Pre-implantation horse conceptuses require nutrients and signals from histotroph, the composition of which is regulated by luteal progesterone and conceptus-secreted factors. To distinguish progesterone and conceptus effects we shortened the period of endometrial progesterone-priming by asynchronous embryo transfer. Day 8 embryos were transferred to synchronous (day 8) or asynchronous (day 3) recipients, and RNA sequencing was performed on endometrium and conceptuses recovered 6 and 11 days later (embryo days 14 and 19). Asynchrony resulted in many more differentially expressed genes (DEGs) in conceptus membranes (3473) than endometrium (715). Gene ontology analysis identified upregulation in biological processes related to organogenesis and preventing apoptosis in synchronous conceptuses on day 14, and in cell adhesion and migration on day 19. Asynchrony also resulted in large numbers of DEGs related to ‘extracellular exosome’. In endometrium, genes involved in immunity, the inflammatory response, and apoptosis regulation were upregulated during synchronous pregnancy and, again, many genes related to extracellular exosome were differentially expressed. Interestingly, only 14 genes were differentially expressed in endometrium recovered 6 days after synchronous versus 11 days after asynchronous transfer (day 14 recipient in both). Among these, KNG1 and IGFBP3 were consistently up-regulated in synchronous endometrium. Furthermore bradykinin, an active peptide cleaved from KNG1, stimulated prostaglandin release by cultured trophectoderm cells. The horse conceptus thus responds to a negatively asynchronous uterus by extensively adjusting its transcriptome, whereas the endometrial transcriptome is modified only subtly by a more advanced conceptus.

Purpose: A number of imaging readout schemes have been proposed for renal arterial spin labelling (ASL) to quantify kidney cortex perfusion, including gradient echo based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo based schemes of spin-echo echo planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T. Methods: Ten healthy volunteers with normal renal function were scanned using each 2D multislice imaging scheme, in combination with a respiratory triggered FAIR (flow-sensitive alternating inversion recovery) ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability. Results: For each imaging scheme, renal cortex perfusion was calculated (bFFE: 276 ± 29 mL/100 g/min, GE-EPI: 222 ± 18 mL/100 g/min, SE-EPI: 201 ± 36 mL/100 g/min, TSE: 200 ± 20 mL/100 g/min). Perfusion was found to be higher for GE based readouts compared to SE based readouts, with significantly higher measured perfusion for the bFFE readout compared to all other schemes (P < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI compared to all other schemes (P < 0.05), the SE-EPI readout gave the highest tSNR and was found to be the most reproducible scheme for the assessment of kidney cortex, with a CoV of 17.2%, whilst minimizing variability of the perfusion weighted signal across slices for whole kidney perfusion assessment. Conclusion: For the assessment of kidney cortex perfusion, SE-EPI provides optimal tSNR, minimal variability across slices and repeatable data acquired in a short scan time with low specific absorption rate.

Terahertz tomography is a promising method among non-destructive inspection techniques to detect faults and defects in dielectric samples. Image quality recently significantly improved through the incorporation of a priori information and off-axis data. However, this improvement has come at the cost of increased measurement time. To aim toward industrial applications, it is therefore necessary to speed up the measurement by parallelizing the data acquisition employing multi-channel setups. In this work, we present two tomographic frequency-modulated continuous wave (FMCW) systems working at a bandwidth of 230-320 GHz, equipped with an eight-channel detector array, and compare their imaging results with a single-pixel setup. While in the first system, the additional channels are used exclusively to detect radiation refracted by the sample, the second system features an f-θ lens, focusing the beam at different positions on its flat focal plane, and thus utilizing the whole detector array directly. The usage of the f-θ lens in combination with a scanning mirror eliminates the necessity of the formerly used slow translation of a single-pixel transmitter. This opens up the potential for a significant increase in acquisition speed, in our case by a factor of four to five, respectively.

Older adults with diabetes are at elevated risk of complications following hospitalization. Home health care services mitigate the risk of adverse events and facilitate a safe transition home. In the United States, when home health care services are prescribed, federal guidelines require they begin within two days of hospital discharge. This study examined the association between timing of home health care initiation and 30-day rehospitalization outcomes in a cohort of 786,734 Medicare beneficiaries following a diabetes-related index hospitalization. Of these patients, 26.6% were discharged to home health care. To evaluate the association between timing of home health care initiation and 30-day rehospitalizations, multivariate logistic regression models including patient demographics, clinical, geographic variables, and neighborhood socio-economic variables were used. Inverse probability-weighted propensity scores were incorporated into the analysis to account for potential confounding between the timing of home health care initiation and the outcome in the cohort. Compared to patients who received home health care within the recommended first two days, patients who received delayed services (3-7 days after discharge) had higher odds of rehospitalization (OR 1.28, 95% CI 1.25-1.32). Among patients who received late services (8-14 days after discharge), the odds of rehospitalization were four times greater than for patients receiving services within 2 days (OR 4.12, 95% CI 3.97-4.28). Timely initiation of home health care following diabetes-related hospitalizations is one strategy to improve outcomes.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Cows produce saliva in very large quantities to lubricate and facilitate food processing. Estimates indicate an amount of 50-150 liter per day. Human saliva has previously been found to contain numerous antibacterial components, such as lysozyme, histatins, members of the S-100 family and lactoferrin to limit pathogen colonization. Cows are dependent of a complex microbial community in their digestive system for food digestion. We wondered how this would influence the content of their saliva. We therefore sampled saliva from five humans and both nose secretions and saliva from six cows and separated the saliva on SDS-PAGE gradient gels and analyzed the major protein bands by LC-MS/MS. The cow saliva was found to be dominated by a few major proteins only, the carbonic anhydrase 6, a pH stabilizing enzyme, and the short palate, lung and nasal epithelium carcinoma-associated protein 2A (SPLUNC2A), also named bovine salivary protein 30kDa (BSP30). This latter protein has been proposed to play a role in local antibacterial response by binding bacterial lipopolysaccharide (LPS) and inhibit bacterial growth, but may instead according to more recent data instead have primarily surfactant activity. Numerous peptide fragments of mucin-5B were also detected in the MS analysis. However, mucins stain poorly by the gel staining solution and they are large and have difficult to enter regular gels why their presence easily are overseen. Interestingly, no major band on gel was detected representing any of the antibacterial proteins indicating that cows may produce them at very low levels not to harm the microbial flora of their digestive system. The nose secretions of the cows primarily contained the odorant protein, a protein thought to be involved in enhancing the sensing of smell by the olfactory receptors to enhance the possibility to quickly sense potential poisonous food components. High levels of secretory IgA was also found in one sample of cow mouth drippings indicating a strong upregulation during an infection. The human saliva we more complex containing both secretory IgA, amylase, carbonic anhydrase 6, lysozyme, histatins and a number of other less abundant proteins.

Zika virus (ZIKV) is a notable arbovirus with maternal, sexual, and TORCH-related transmission capabilities. After 2015, Brazil had the highest number of ZIVK-infected pregnant women who lost their babies or delivered them with Congenital ZIKV Syndrome (CZS). ZIKV infection has been linked to variations in endogenous retroviruses (ERVs) and interleukins within the placenta. ERVs, remnants of ancient viral infections integrated into the genome, include syncytin receptors crucial for placental development. Interleukins, immune response regulators, aid immune tolerance and support syncytial structure development in the placenta, where syncytin receptors facilitate vital cell-to-cell fusion events. Since ZIKV can infect trophoblast cells, we investigated the relationship between ZIKV infections and ERV and interleukin modulations. Investigating the impact of ZIKV on trophoblast cells, we examined two cell types (BeWo and HTR8) infected with ZIKV-MR766 (African) and ZIKV-IEC-Paraíba (Asia-Brazilian) using Taqman and RT2 Profiler PCR Array assays. While early ZIKV infection (24-48 hours) did not induce differential ERV and interleukin expression, future studies involving additional trophoblastic cell lineages and extended infection timelines will illuminate the dynamic interplay between ZIKV, HERVs, interleukins, and cytokines essential for placental formation and function.

Background: Quality of life (QoL) in IC/BPS patients is an evidence gap in guidelines, because studies are limited and outdated. Therefore, guidelines might not reflect the current situation accurately, and no possible improvements in QoL of these patients. Secondly, guidelines suggest multimodal approach in therapy, however unknown is how the efficacy of these therapies are perceived by the patient themselves. The aim of this study is to investigate the perception of IC/BPS patients on their QoL and to determine which treatments they received and how they evaluate the efficacy of these various (alternative) therapies.Methods: Quantitative retrospective database study in IC/BPS patients, compiled of existing patient survey data (n=217) from July 2021. Results: The QoL of patients is affected significantly by IC/BPS. This is evident from the substantial self-reported impact by patients, the various affected domains on EQ-5D 5L. The QoL was not negatively affected by delayed diagnosis, but there were differences between female and males. Secondly, there was the wide array of (alternative) treatments utilized, although some have doubtful results and high dropout rates. Conclusion: QoL is considerably impaired in IC/BPS patients. Coagulation therapy and intravesical GAG therapy were most appreciated treatments. The diverse responses and adherence to various treatments warrant a personalized approach (phenotype-oriented therapy). To achieve improvement in the QoL, it is important to incorporate the patient’s perspective in treatment guidelines.

As a consequence of the increasing share of renewable energies and sector coupling technologies, new approaches are needed for the study, planning, and control of modern energy systems. Such new structures may add extra stress to the electric grid, as is the case with heat pumps and electrical vehicles. Therefore, the optimal performance of the system must be estimated considering the constraints imposed by the different sectors. In this research, a dispatch optimization method with an iterative grid constraint generation, decoupled from the linear unit commitment problem, is employed. From the considered scenarios, it was found that in a typical German neighborhood with 150 households, PV penetration of ∼5kWp per household can lead to curtailment of ∼60MWh per year due to line loading. Furthermore, the proposed method eliminates grid violations due to the addition of new sectors reducing the curtailment up to 60%. With the optimization of the heat pump operation, an increase of 7% of the self-consumption was achieved with similar results for the combination of battery systems and electrical vehicles. In conclusion, a safer and optimal operation of a complex energy system is fulfilled. Safer control strategies and more accurate plant sizing could be derived from this work.

This study explores the impact of the ‘pre-intervention effects’ of a community-based interventions. This refers to participatory research processes and parallel publicity in the media on changes in alcohol use and relevant mechanisms (rules and norms about alcohol, accessibility of alcohol in a formal setting) among adolescents before any intervention is implemented. In a quasi-experimental study, adolescent data were collected twice by means of self-report among adolescents living in two municipalities (control and experimental condition). Regression analysis showed pre-intervention main effects on adolescents’ perceived accessibility of alcohol in a formal setting. Moreover, among adolescents aged 15 years and older, the normative decline in strictness of rules and norms was less steep in the experimental condition compared to the control condition. Also, adolescents aged 14 years and younger in the experimental condition reported more weekly drinking compared to their peers in the control condition. No differential effects across gender were found. To conclude, applying a co-creational approach in the development of an intervention, not only contributes to more effective interventions in the end, but involvement of and discussions in the community at the start of intervention planning are contributing to changes in targeted factors. This implies that public discussions about the development of intervention strategies should be considered as an essential feature of co-creation in community-based interventions.

Oryzias latipes is an important model organism for physiology, genetics and developmental studies, and has also emerged a relevant vertebrate model for aquatic ecotoxicology. Knowledge regarding its associ-ated microbiota on the other hand is still scarce and limited to adults, despite the relevance of associated microbiome to hosts biology. This study provides first insights into the establishment of bacterial mi-crobiota during early developmental stages of laboratory-reared medaka using a 16SrRNA sequenc-ing-based approach. Major shifts in community compositions are observed, from a Proteobacte-ria-dominated community in larvae and juveniles to a more phylum diverse community towards adult-hood, with no obvious difference between female and male specimens. Major bacterial taxa found in adults, including genera Cetobacterium and ZOR0006, establish progressively and are rare during early stages. Dominance shifts are comparable to those documented in another major model teleost, the zebrafish. Results from this study provide a basis for future work investigating the influence of meda-ka-associated bacteria during host development.

In this review, we provide an overview of the current knowledge on the different sexual systems and sex determining mechanisms in bivalves, with a focus on the various epigenetic and genetic factors that may be involved. The final section of the review provides recent discoveries on sex-specific mitochondrial genes in bivalves possessing the unconventional system of doubly uniparental inheritance of mitochondria (which is found in several members of the orders Mytiloida, Unionoida, Veneroida and Nuculanoida). The genes involved in this developmental pathway could represent the first sex determination system in animals in which mitochondrially-encoded genes are directly involved.

Smartwatches are one of the most relevant fitness trends of the past two decades, and they collect increasing amounts of health and movement data. The accuracy of these data may be questionable and requires further investigation. Therefore, the aim of the present study is to validate smartwatches for use in triathlon training. Ten different smartwatches were tested for accuracy in measuring heart rate, distance (via global navigation satellite systems, GNSS), swim stroke rates and the number of swim laps in a 50 m Olympic-size pool. The optical heart rate measurement function of each smartwatch was compared to that of a chest strap. Thirty participants (15 females, 15 males) ran five 3-minute intervals on a motorised treadmill to evaluate the accuracy of the heart rate measurements. Moreover, for each smartwatch, running und cycling distance tracking was tested over six runs of 4,000 m on a 400 m tartan stadium track, six hilly outdoor runs over 3.4 km, and four repetitions of a 36.8 km road bike course, respectively. Three swimming protocols ranging from 200 m to 400 m were performed in triplicate in a 50 m Olympic-size pool, evaluating tracked distance and detected number of strokes. The mean absolute percentage errors (MAPEs) for the average heart rate measurements varied between 3.1% and 8.3%, with the coefficient of determination ranging from 0.22 to 0.79. MAPE results ranged from 0.8% to 12.1% for the 4,000 m run on the 400 m track, from 0.2% to 7.5% for the 3.4 km outdoor run, and from 0.0% to 4.2% for the 36.8 km bike ride. For the swimming tests, in contrast, the deviations from the true distance varied greatly, starting at a 0.0% MAPE for the 400 m freestyle and reaching 91.7% for the 200 m medley with style changes every 25 m. In summary, for some of the smartwatches, the measurement results deviated substantially from the true values. Measurements taken while road cycling over longer distances with only a few curves were in relative terms more accurate than for outdoor runs and even more accurate than for the 400 m track. In the swimming exercises, the accuracy of the measured distances was severely deteriorated by the medley changes among the majority of the smartwatches. Altogether, the results of this study should help in assessing the accuracy and thus suitability of smartwatches for general triathlon training.

Corneal diseases are the third leading cause of blindness worldwide. There are numerous causes of corneal blindness, and the common treatment for this condition often involves corneal tissue transplantation, such as Descemet's Membrane Endothelial Keratoplasty (DMEK). DMEK has been established as the preferred surgical technique for the treatment of corneal endothelial disorders. The success of DMEK depends largely on the quality of the donor endothelial cells and the trans-plantation procedure. However, the scarcity of suitable donor tissue and the sensitivity of endo-thelial cells pose a major challenge. In recent years, tissue engineering has attracted attention as potential solutions to these problems. This review offers an outline of the current landscape of DMEK in the context of bioengineering, exploring various methodologies, advancements, and fu-ture prospects.

Obesity is a significant public health concern with higher morbidity. Obesity patients are at risk of severe COVID-19 infection and obesity is a higher risk factor for intensive Care Unit admission in COVID-19 infection. Obesity status affects lung volumes, cardiac structure and hemodynamics. Obesity is associated with a low inflammation state, endothelial dysfunction, hyperinsulinaemia and metabolic disorders. The authors review cardio-respiratory pathophysiological aspects involved in obesity and propose clinical management in obese patients infected by COVD-19.

Background: The UK dairy sheep industry is relatively small but growing, particularly for cheese and yogurt products. Anecdotally, sheep milk (SM) is better tolerated by humans than cows’ milk and could have environmental as well as health benefits. All milk contains sub-micron particles called extracellular vesicles (EV) which are mainly derived from the mammary epithelium. Physiologically, milk derived EV are thought to aid development of infant immunity and the microbiome but may also have health benefits to adult humans. Methods: Using sequential ultracentrifugation vesicles of &lt;1µm (LEV) followed by &lt;200nm (sEV) were isolated from six individual sheep during mid lactation. RNA was extracted and microRNA analysed by RTqPCR for sequences previously identified in cows’ milk. Human THP-1 monocytes were differentiated into macrophages and incubated with SM-derived LEV and sEV in the presence of pro-inflammatory LPS to measure effects on secretion of the chemokine CCL-2 or in the presence of DMNQ and fluorescent dihydrorhodamine-1,2,3 to measure reactive oxygen species. Results: LEV induced an increase in ROS in both monocytes and macrophages, whilst sEV decreased DMNQ-mediated ROS in macrophages but not monocytes. Interestingly, the LEV did not induce CCL2 release, however they increased LPS-induced CCL2 secretion in monocytes but not macrophages. miR26a, miR92a, miR125b, miR155, miR223, were identified in both sEV and LEV by RT-qPCR and could be responsible for modulation of ROS and CCL2 expression. Conclusions: These findings suggest that sheep milk can influence human monocyte/macrophage responses and so is worthy of further investigation for its potential human and non-human animal health benefits.

The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).

Based on a measuring system to determine levels of spatial organization in 2D polygons (homogeneous or heterogeneous partition of defined areas) lying on principles of regularity, we propose the entropy term linked to the concept of “information”, from the “information theory field”, in order to obtain an information measurement regarding a quantity of or amount of information in the architecture of complex 2D biological organizations. The term “quantity” does not refer to the amount of data (size), but to the probability of a geometrical basic pattern within a set of possible statistical configurations regarding levels of homogeneity and heterogeneity. It is this notion of information that is important in information theory, and measures of information in units of bits, what we propose to use for measuring quantities of organization in the architecture of complex geometrical systems. Two complex systems are tested, biological and non biological in order to obtain experimental results, which are verified with the evaluation criteria “entropy”. Experimental results show that the lowest levels of information and entropy, in addition with low rates of heterogeneity and high rates of homogeneity are particular features of geometrical organizations in biological systems.

Transient conjugate heat transfer measurements under varying temperature and velocity inlet boundary conditions at incompressible flow conditions were performed for flat plate and ribbed channel geometries. Therefrom local adiabatic wall temperatures and heat transfer coefficients are determined. Those data are analyzed using typical heat transfer correlations, e.g. Nu=CRe^mPr^n determining the local distribution of C and m. It is shown that they are closely linked. A relationship lnC=A−mB is observed with A and B as modeling parameters. They could be related to parameters in log law or power law representations for turbulent boundary layer flows. The parameter m is shown to have a close link to local pressure gradients and therewith near wall streamlines as well as friction factor distributions. A normalization of the C parameter allows to derive a Reynolds analogy factor and therefrom local wall shear stresses.

Background Natural Saccharomyces cerevisiae yeast strains exhibit very large genotypic and phe-notypic diversity. Breeding programs taking advantage of this characteristic, are widely used for yeast selection in the wine industry, especially in the recent years when winemakers need to adapt their production to climate change. The aim of this work was to evaluate a Marker Assisted Se-lection (MAS) program to improve malic acid consumption capacity of Saccharomyces cerevisiae in grape juice. Methods Optimal individuals of two unrelated F1-hybrids were crossed to get a new genetic background carrying many “malic consumer” loci. Then, eleven QTLs already identified were used for implementing the MAS breeding program. Results By this way, extreme individuals able to consume more than 70% of malic acid in grape juice were selected. These individuals were tested in different enological matrixes and compared to their original parental strains. They greatly reduced the malic acid content at the end of alcoholic fermentations, they appeared to be robust to the environment and accelerate the ongoing of malo-lactic fermentations by Oenococcus oeni. Conclusions This study illustrates how MAS can be efficiently used for selecting industrial Saccharomyces cerevisiae strains with outlier properties for winemaking.

SORL1 gene encodes LR11/SorLA, a protein that binds -amyloid precursor protein (bAPP) and drives its intracellular trafficking. SORL1 mutations occurring frequently in a subset of familial cases of Alzheimer’s disease (AD) have been documented but their pathogenic potential is not yet clear and questions remain concerning their putative influence on the physiopathological processing of bAPP. We have assessed the influence of three SORL1 mutations that were described as likely disease-causing and that were associated with either benign (SorLA924) or severe (SorLA141 and SorLA511) AD phenotypes. We examined the influence of wild-type and mutants SorLA in transiently transfected HEK293 cells expressing either wild-type or Swedish mutated bAPP on bAPP expression, secreted Ab and sAPPa levels, intracellular Ab40 and Ab42 peptides, APP-CTFs (C99 and C83) expressions, a-, b- and g-secretases expressions and activities as well as Ab and CTFs-degrading enzymes. These paradigms were studied in control conditions or after pharmacological proteasomal modulation. We also established stably transfected CHO cells expressing wild-type SorLA and established the colocalization of wild-type SorLA and bAPP. Overall, although we mostly confirmed previous data concerning the influence of wild-type SorLA on bAPP processing, we were unable to evidence significant alterations triggered by our set of SorLA mutants, whatever the cells or pharmacological conditions examined. Our study however does not rule out the possibility that other AD-linked SORL1 mutations could indeed affect bAPP processing and that pathogenic mutations examined in the present study could interfere with other cellular pathways/triggers in AD.

Background and Aims: Screening and assessment of cognitive changes in adults with Intellectual Disabilities, mainly Down Syndrome (DS), is crucial to offer appropriate services to their needs. We present a systematic review of the existing instruments assessing dementia, aiming to support researchers and clinicians’ best practice. Methods: Searches were carried out in the databases Web of Science; PubMed; PsycINFO in March 2019 and updated in May 2020. Studies were selected and examined if they: (1) focused on assessing age-related cognitive changes in person with ID; (2) included adults and/or older adults; (3) included scales and batteries for cognitive assessment. Results: Forty-eight cross-sectional studies and twenty-six longitudinal studies were selected representing a total sample of 5,851 participants (4,089 DS and 1,801 with other ID). In those studies, we found 38 scales, questionnaires, and inventories, and 14 batteries for assessing cognitive and behavioural changes in adults with DS and other ID. Conclusion: The most used instrument completed by an informant or carer was the Dementia Questionnaire for Learning Disabilities (DLD), and its previous versions. We discuss the strengths and limitations of the instruments and outline recommendations for future use.