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Background: Inhibition of platelet responsiveness is important for controlling thrombosis. It is well established that platelet endothelial cell adhesion molecule-1 (PECAM-1) serves as a physiological negative regulator of platelet-collagen interactions. We recently demonstrated that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a negative regulator of platelet production and reactivity. It is however not known if LAIR-1 and PECAM-1 function in the same or different inhibitory pathways. Objectives: In this study, we investigated the role of LAIR-1 alongside PECAM-1 in megakaryocyte development and platelet production and determined the functional redundancy through characterization of a LAIR-1/PECAM-1 double knockout (DKO) mouse model. Methods: LAIR-1 and PECAM-1 expression in megakaryocytes were evaluated by western blotting. Megakaryocyte ploidy and proplatelet formation were evaluated by flow cytometry and fluorescent microscopy. Platelet function and signalling were compared in wild-type, LAIR-1−/−, PECAM-1−/− and DKO mice using aggregometry, flow cytometry and western blotting. Thrombosis was evaluated using the FeCl3 carotid artery model. Results: We show that LAIR-1/PECAM-1 DKO mice exhibit a 17% increase in platelet count. Bone marrow-derived megakaryocytes from all 3 mouse models had normal ploidy in vitro, suggesting that neither LAIR-1 nor PECAM-1 regulates megakaryocyte development. Furthermore, relative to wild-type platelets, platelets derived from LAIR-1, PECAM-1, and DKO mice were equally hyperresponsive to collagen in vitro, indicating that LAIR-1 and PECAM-1 participate in the same inhibitory pathway. Interestingly, DKO mice exhibited normal thrombus formation in vivo due to DKO mouse platelets lacking the enhanced Src family kinase activation previously shown in platelets from LAIR-1-deficient mice. Conclusion: Findings from this study reveal that LAIR-1 and PECAM-1 act to inhibit GPVI-mediated platelet activation via the same signaling pathway. Mice lacking LAIR-1 and PECAM-1 do not however exhibit an increase in thrombus formation despite minor increase in platelet count and reactivity to collagen. This study adds to the growing evidence that immunoreceptor tyrosine-based inhibition motif–containing receptors are important regulators of platelet count and function.

IntroductionMortality of the riparian alder population caused by Phytophthora pathogens has been studied for over 20 years throughout Europe, recently gaining more importance in the context of evident climate change. The main objective of this study was to examine the pathogenicity of species from the “Phytophthora alni complex” present in the Czech Republic (P. × alni and P. uniformis) and P. plurivora to Alnus glutinosa seedlings grown at ambient and elevated CO2 concentration.MethodsAn underbark inoculation test was performed with seedlings grown from seeds collected from two Czech alder populations, one suffering from severe Phytophthora decline and the other disease-free.ResultsThe results showed significant differences in lesion development and seedling mortality. After a 13-week experimental period, at both CO2 levels P. × alni and P. uniformis showed high aggressiveness to A. glutinosa seedlings causing lesions of variable sizes and mortality of 33.3%, and 45.8% of plants, respectively. In contrast, P. plurivora did not cause mortality to any plant, and lesion sizes did not differ significantly from those in control plants. Physiological measurements did not reveal any significant differences between Phytophthora species except for plants inoculated with P. plurivora showing increased values in specific physiological parameters 4 weeks post-inoculation. Net photosynthesis decreased over the measurement period in all treatments with significant differences found between measurements conducted 2 and 4 weeks after the inoculation. Transpiration showed a decreasing trend in all inoculated plants with no significant differences between Phytophthora species at both CO2 levels. Chemical analyses of root samples showed high variability in sugars and phenolic compounds related to the plant's health status.DiscussionThis is the first study to examine the response of alder seedlings to Phytophthora pathogens at different CO2 levels. The findings demonstrate high aggressiveness of P. × alni and P. uniformis and weaker aggressiveness of P. plurivora to alder seedlings regardless of the CO2 level.

The pharmaceutical industry is looking for new and innovative ways of manufacturing to improve product quality and reduce process complexity. In manufacturing oral solid dosage products, blending is a crucial step in ensuring the homogeneity of active pharmaceutical ingredients (APIs) in the final product. Currently, batch and continuous blending are the two commonly used modes for blending in the industry. However, these methods have limitations in terms of blending time, manual intervention, and flexibility in handling multiple ingredients. To address these limitations, this study aims to explore the feasibility and benefits of using a semicontinuous blending mode in the pharmaceutical industry. A case study is conducted using a binary blend of microcrystalline cellulose and acetaminophen to compare the performance of the semicontinuous mode of blending with the batch and continuous blending modes. The results show that the semicontinuous blending setup can produce blends with good blend uniformity and homogeneity and that the output can be used for both batch and continuous downstream operations. The effect of variation in the three most important process parameters, impeller rotation per minute, blending time, and fill level on the blend uniformity, is also investigated. The semicontinuous blending mode had a higher line rate of 12.5 kg/hour than a similarly sized batch blender at 3.6 kg/hour and less than that of a continuous blender. The benefits of the new blending mode include reduced blending time, minimal manual intervention, flexibility in blending multiple ingredients, easier scale-up, and a smaller footprint. Overall, this study highlights the relative advantages of using this new semicontinuous blending mode in pharmaceutical manufacturing and its potential as a good alternative to the existing blending modes. The semicontinuous mode is well placed between the batch blending and continuous blending mode, with many benefits over the former mode and performance comparable to the latter continuous mode.

Abstract The COVID-19 pandemic caused lifestyle changes and has led to the new electricity demand patterns in the presence of non-pharmaceutical interventions such as work-from-home policy and lockdown. Quantifying the effect on electricity demand is critical for future electricity market planning yet challenging in the context of limited smart metered buildings, which leads to limited understanding of the temporal and spatial variations in building energy use. This study uses a large scale private smart meter electricity demand data from the City of Austin, combined with publicly available environmental data, and develops an ensemble regression model for long term daily electricity demand prediction. Using 15-min resolution data from over 400,000 smart meters from 2018 to 2020 aggregated by building type and zip code, our proposed model precisely formalizes the counterfactual universe in the without COVID-19 scenario. The model is used to understand building electricity demand changes during the pandemic and to identify relationships between such changes and socioeconomic patterns. Results indicate the increase in residential usage , demonstrating the spatial redistribution of energy consumption during the work-from-home period. Our experiments demonstrate the effectiveness of our proposed framework by assessing multiple socioeconomic impacts with the comparison between the counterfactual universe and observations.

IntroductionPro-thrombotic events are one of the prevalent causes of intensive care unit (ICU) admissions among COVID-19 patients, although the signaling events in the stimulated platelets are still unclear.MethodsWe conducted a comparative analysis of platelet transcriptome data from healthy donors, ICU, and non-ICU COVID-19 patients to elucidate these mechanisms. To surpass previous analyses, we constructed models of involved networks and control cascades by integrating a global human signaling network with transcriptome data. We investigated the control of platelet hyperactivation and the specific proteins involved.ResultsOur study revealed that control of the platelet network in ICU patients is significantly higher than in non-ICU patients. Non-ICU patients require control over fewer proteins for managing platelet hyperactivity compared to ICU patients. Identification of indispensable proteins highlighted key subnetworks, that are targetable for system control in COVID-19-related platelet hyperactivity. We scrutinized FDA-approved drugs targeting indispensable proteins and identified fostamatinib as a potent candidate for preventing thrombosis in COVID-19 patients.DiscussionOur findings shed light on how SARS-CoV-2 efficiently affects host platelets by targeting indispensable and critical proteins involved in the control of platelet activity. We evaluated several drugs for specific control of platelet hyperactivity in ICU patients suffering from platelet hyperactivation. The focus of our approach is repurposing existing drugs for optimal control over the signaling network responsible for platelet hyperactivity in COVID-19 patients. Our study offers specific pharmacological recommendations, with drug prioritization tailored to the distinct network states observed in each patient condition. Interactive networks and detailed results can be accessed at https://fostamatinib.bioinfo-wuerz.eu/.

Abstract Introduction The motor‐related bioelectric brain activity of healthy young and old subjects was studied to understand the effect of aging on motor execution. A visually cued finger tapping movement paradigm and high‐density EEG were used to examine the time and frequency characteristics. Methods Twenty‐two young and 22 healthy elderly adults participated in the study. Repeated trials of left and right index finger movements were recorded with a 128‐channel EEG. Event‐Related Spectral Perturbation (ERSP), Inter Trial Coherence (ITC), and Functional Connectivity were computed and compared between the age groups. Results An age‐dependent theta and alpha band ERSP decrease was observed over the frontal–midline area. Decrease of beta band ERSP was found over the ipsilateral central–parietal regions. Significant ITC differences were found in the delta and theta bands between old and young subjects over the contralateral parietal–occipital areas. The spatial extent of increased ITC values was larger in old subjects. The movement execution of older subjects showed higher global efficiency in the delta and theta bands, and higher local efficiency and node strengths in the delta, theta, alpha, and beta bands. Conclusion As functional compensation of aging, elderly motor networks involve more nonmotor, parietal–occipital, and frontal areas, with higher global and local efficiency, node strength. ERSP and ITC changes seem to be sensitive and complementary biomarkers of age‐related motor execution.

Measurement(s) room temperature ambient air • room relative humidity • outdoor weather • window status • door status • fan status • HVAC measurement • lighting status • occupancy measurement • plug load • shade status Technology Type(s) Temperature Sensor Device • relative humidity sensor • weather station • window status sensor • door status sensor • fan status sensor • HVAC measurement sensors • lighting sensor • occupancy sensor • power sensor • shade status sensor

Raman spectroscopy is one of the important process analytical technology tools available for implementation in the continuous manufacturing of oral solid dosages. The aim of this study was to investigate several practical considerations in generating real-time measurements using Raman spectrometer at a tablet press feed frame, including the effects of fluorescence interference, photobleaching, feed-frame rpm, and material particle size. Fluorescence, in particular, is a significant drawback of Raman spectroscopy, compared to the use of near-infrared spectroscopy. Potential material sparing strategies were also investigated, including using stationary powders for calibration and isolation of feed-frame materials. Acetaminophen was used as the main active pharmaceutical ingredient (API), and microcrystalline cellulose (MCC) and lactose were used as excipients. The fluorescent behavior of MCC at 785 nm laser wavelength was reported and discussed. Raman spectra of a blend of MCC and acetaminophen and lactose and acetaminophen were collected at the feed frame of the tablet press. A series of preprocessing steps applied to remove the fluorescence interference was found to be effective, including the use of standard normal variate, subtraction of spectra of fluorescent material, baseline correction, and smoothing. Three different PLS models were prepared for different scenarios and their performances were compared. The models were able to predict the concentration of acetaminophen with root mean squared error prediction (RMSEP) of 0.29% w/w when there was no fluorescence interference and 0.57% w/w when there was fluorescence interference in background spectra. The study demonstrated the feasibility of using Raman spectroscopy for API concentration prediction even in the case of fluorescent interference and showed that Raman measurements were robust; that is, they were not much affected by feed-frame rpm and excipient particle size.

Building upon prior research that highlighted the need for standardizing environments for building control research, and inspired by recently introduced challenges for real life reinforcement learning (RL) control, here we propose a non-exhaustive set of nine real world challenges for RL control in grid-interactive buildings (GIBs). We argue that research in this area should be expressed in this framework in addition to providing a standardized environment for repeatability. Advanced controllers such as model predictive control (MPC) and RL control have both advantages and disadvantages that prevent them from being implemented in real world problems. Comparisons between the two are rare, and often biased. By focusing on the challenges, we can investigate the performance of the controllers under a variety of situations and generate a fair comparison. As a demonstration, we implement the offline learning challenge in CityLearn, an OpenAI Gym environment for the easy implementation of RL agents in a demand response setting to reshape the aggregated curve of electricity demand by controlling the energy storage of a diverse set of buildings in a district. We use CityLearn to study the impact of different levels of domain knowledge and complexity of RL algorithms and show that the sequence of operations (SOOs) utilized in a rule based controller (RBC) that provides fixed logs to RL agents during offline training affect the performance of the agents when evaluated on a set of four energy flexibility metrics. Longer offline training from an optimized RBC leads to improved performance in the long run. RL agents that train on the logs from a simplified RBC risk poorer performance as the offline training period increases. We also observe no impact on performance from information sharing amongst agents. We call for a more interdisciplinary effort of the research community to address the real world challenges, and unlock the potential of GIB controllers.

C-type lectin-like receptor 2 (CLEC-2) is considered as a potential drug target in settings of wound healing, inflammation, and infection. A potential barrier to this is evidence that CLEC-2 and its ligand podoplanin play a critical role in preventing lymphatic vessel blood filling in mice throughout life. In this study, this aspect of CLEC-2/podoplanin function is investigated in more detail using new and established mouse models of CLEC-2 and podoplanin deficiency, and models of acute and chronic vascular remodeling. We report that CLEC-2 expression on platelets is not required to maintain a barrier between the blood and lymphatic systems in unchallenged mice, post-development. However, under certain conditions of chronic vascular remodeling, such as during tumorigenesis, deficiency in CLEC-2 can lead to lymphatic vessel blood filling. These data provide a new understanding of the function of CLEC-2 in adult mice and confirm the essential nature of CLEC-2-driven platelet activation in vascular developmental programs. This work expands our understanding of how lymphatic blood filling is prevented by CLEC-2-dependent platelet function and provides a context for the development of safe targeting strategies for CLEC-2 and podoplanin.

Abstract Sarcoma (Src) family kinases (SFKs) have occupied a central place in platelet research for over 40 years. Discovered by virologists and oncologists as the proto proto‐oncogene, Src tyrosine kinase spurred a phenomenal burst of research on reversible tyrosine phosphorylation and signal transduction. For a time, platelets were adopted as the model of choice for studying the biological functions of Src, owing to their ease of isolation, high Src expression, and lack of a nucleus, only to be abandoned due to challenges of culturing and manipulating using common molecular biology‐based techniques. For platelet biologists, SFKs have remained an important area of investigation, initiating and amplifying signals from all major adhesion, activation, and inhibitory receptors, including the integrin αIIbβ3, the collagen receptor complex glycoprotein VI–Fc receptor γ‐chain, the G protein–coupled ADP receptor P2Y12 and the inhibitory receptors platelet endothelial cell adhesion molecule‐1 and G6b‐B. The vital roles of SFKs in platelets is highlighted by the severe phenotypes of null and gain‐of‐function mutations in SFKs in mice and humans, and effects of pharmacologic inhibitors on platelet activation, thrombosis, and hemostasis. The recent description of critical regulators of SFKs in platelets, namely, C‐terminal Src kinase (Csk), Csk homologous kinase (Chk), the receptor‐type protein‐tyrosine phosphatase receptor type J (PTPRJ) helps explain some of the bleeding side effects of tyrosine kinase inhibitors and are novel therapeutic targets for regulating the thrombotic and hemostatic capacity of platelets. Recent findings from Chk, Csk, and PTPRJ knockout mouse models highlighted that SFKs are able to autoinhibit by phosphorylating their C‐terminal tyrosine residues, providing fundamental insights into SFK autoregulation.

The Total Thrombus-formation Analyser System (T-TAS) is a whole blood flow chamber system for the measurement of in vitro thrombus formation under variable shear stress conditions. Our current study sought to evaluate the potential utility of the T-TAS for the measurement of thrombus formation within human and mouse whole blood. T-TAS microchips (collagen, PL chip; collagen/tissue thromboplastin, AR chip) were used to analyze platelet (PL) or fibrin-rich thrombus formation, respectively. Blood samples from humans (healthy and patients with mild bleeding disorders) and wild-type (WT), mice were tested. Light transmission lumi-aggregometer (lumi-LTA) was performed in PRP using several concentrations of ADP, adrenaline, arachidonic acid, collagen, PAR-1 peptide and ristocetin. Thrombus growth (N = 22) increased with shear within PL (4:40 ± 1.11, 3:25 ± 0.43 and 3:12 ± 0.48 mins [1000, 1500 and 2000s−1]) and AR chips (3:55 ± 0.42 and 1:49 ± 0.19 [240s−1 and 600s−1]). The area under the curve (AUC) on the PL chip was also reduced at 1000s−1 compared to 1500/2000s−1 (260 ± 51.7, 317 ± 55.4 and 301 ± 66.2, respectively). In contrast, no differences in the AUC between 240s−1 and 600s−1 were observed in the AR chip (1593 ± 122 and 1591 ± 158). The intra-assay coefficient of variation (CV) (n = 10) in the PL chip (1000s−1) and AR chip (240s−1) were T1014.1%, T6016.7%, T10-6022.8% and AUC1024.4% or T10 9.03%, T808.64%, T10-8023.8% and AUC305.1%. AR chip thrombus formation was inhibited by rivaroxaban (1 µM), but not with ticagrelor (10 µM). In contrast, PL chip thrombus formation was totally inhibited by ticagrelor. T-TAS shows an overall agreement with lumi-LTA in 87% of patients (n = 30) with normal PL counts recruited into the genotyping and phenotyping of platelet (GAPP) study and suspected to have a PL function defect. The onset (T10) of thrombus formation in WT mice (N = 4) was shorter when compared to humans e.g. PL chip (1000s−1) T10 were 02:02 ± 00:23 and 03:30 ± 0:45, respectively). T-TAS measures in vitro thrombus formation and can be used for monitoring antithrombotic therapy, investigating patients with suspected PL function defects and monitoring PL function within mice.

Mycotoxins originating in the preharvest period represent a less studied research problem, even though they are of the utmost practical significance in maize production, determining marketability (within EU limits), and storage ability, competitiveness, and profit rate. In this study, 18–23 commercial hybrids were tested between 2014 and 2021. Natural infection from Fusarium spp. was higher than 1.5%, and for Aspergillus spp. this was normally 0.01% or 0, much lower than would be considered as severe infection. In spite of this, many hybrids provided far higher toxin contamination than regulations allow. The maximum preharvest aflatoxin B1 was in 2020 (at 2286 μg/kg), and, in several cases, the value was higher than 1000 μg/kg. The hybrid differences were large. In Hungary, the presence of field-originated aflatoxin B1 was continuous, with three AFB1 epidemics in the 8 years. The highest DON contamination was in 2014 (at 27 mg/kg), and a detectable DON level was found in every hybrid. FUMB1+B2 were the highest in 2014 (at 45.78 mg/kg). At these low infection levels, correlations between visual symptoms and toxin contaminations were mostly non-significant, so it is not feasible to draw a conclusion about toxin contamination from ear rot coverage alone. The toxin contamination of hybrids for a percentage of visual infection is highly variable, and only toxin data can decide about food safety. Hybrids with no visual symptoms and high AFB1 contamination were also identified. Preharvest control, including breeding and variety registration, is therefore of the utmost importance to all three pathogens. Even natural ear rot and toxin data do not prove differences in resistance, so a high ear rot or toxin contamination level should be considered as a risk factor for hybrids. The toxin control of freshly harvested grain is vital for separating healthy and contaminated lots. In addition, proper growing and storage conditions must be ensured to protect the feed safety of the grain.

Coordinated rearrangements of the actin cytoskeleton are pivotal for platelet biogenesis from megakaryocytes but also orchestrate key functions of peripheral platelets in hemostasis and thrombosis, such as granule release, the formation of filopodia and lamellipodia, or clot retraction. Along with profilin (Pfn) 1, thymosin β4 (encoded by Tmsb4x) is one of the two main G-actin-sequestering proteins within cells of higher eukaryotes, and its intracellular concentration is particularly high in cells that rapidly respond to external signals by increased motility, such as platelets. Here, we analyzed constitutive Tmsb4x knockout (KO) mice to investigate the functional role of the protein in platelet production and function. Thymosin β4 deficiency resulted in a macrothrombocytopenia with only mildly increased platelet volume and an unaltered platelet life span. Megakaryocyte numbers in the bone marrow and spleen were unaltered, however, Tmsb4x KO megakaryocytes showed defective proplatelet formation in vitro and in vivo. Thymosin β4-deficient platelets displayed markedly decreased G-actin levels and concomitantly increased F-actin levels resulting in accelerated spreading on fibrinogen and clot retraction. Moreover, Tmsb4x KO platelets showed activation defects and an impaired immunoreceptor tyrosine-based activation motif (ITAM) signaling downstream of the activating collagen receptor glycoprotein VI. These defects translated into impaired aggregate formation under flow, protection from occlusive arterial thrombus formation in vivo and increased tail bleeding times. In summary, these findings point to a critical role of thymosin β4 for actin dynamics during platelet biogenesis, platelet activation downstream of glycoprotein VI and thrombus stability.

The formation of polysubstituted cyclopropane derivatives in the gold(I)-catalyzed reaction of olefins and propargylic esters is a potentially useful transformation to generate diversity, therefore any method in which its stereoselectivity could be controlled is of significant interest. We prepared and tested a series of chiral gold(I)-carbene complexes as a catalyst in this transformation. With a systematic optimization of the reaction conditions, we were able to achieve high enantioselectivity in the test reaction while the cis:trans selectivity of the transformation was independent of the catalyst. Using the optimized conditions, we reacted a series of various olefins and acetylene derivatives to find that, although the reactions proceeded smoothly and the products were usually isolated in good yield and with good to exclusive cis selectivity, the observed enantioselectivity varied greatly and was sometimes moderate at best. We were unable to establish any structure-property relationship, which suggests that for any given reagent combination, one has to identify individually the best catalyst.

Due to the population’s growing need for energy and the increasing impact of the phenomena of global warming and climate change on a global level, it becomes imperative to diminish energy consumption worldwide. For this reason, a deeper understanding of factors that encourage energy-saving habits and overall lifestyle is required. This research examined the factors that hold an impact on the adoption of energy-saving habits in Romania. It used eight constructs that were checked to see if they influence the individuals’ intentions to save energy. The research used a quantitative analysis approach, with primary data assembled through a survey of the population from six developed counties in Romania. In order to investigate and assess the data, structural equation modeling (SEM) was used. The results show that environmental awareness, perceived consumer effectiveness and a collectivistic perspective affect individuals in implementing energy-saving habits (in their life) in a significant and positive way. However, resistance to change and perceived costs were identified as having a negative and significant impact on the individuals’ implementation of such habits within their households. The outcomes of this research play a part in raising awareness of what could determine a more energy-saving lifestyle, and therefore it is essential that stakeholders within the energy sector in Romania consider the aspects of environmental awareness, perception of consumer effectiveness, perceived costs, collectivism and resistance to change during the development of programs of energy efficiency.

Dynamic interdependencies within and between physiological systems and subsystems are key for homeostatic mechanisms to establish an optimal state of the organism. These interactions mediate regulatory responses elicited by various perturbations, such as the high-pressure baroreflex and cerebral autoregulation, alleviating the impact of orthostatic stress on cerebral hemodynamics and oxygenation. The aim of this study was to evaluate the responsiveness of the cardiorespiratory-cerebrovascular networks by capturing linear and nonlinear interdependencies to postural changes. Ten young healthy adults participated in our study. Non-invasive measurements of arterial blood pressure (from that cardiac cycle durations were derived), breath-to-breath interval, cerebral blood flow velocity (BFV, recorded by transcranial Doppler sonography), and cerebral hemodynamics (HbT, total hemoglobin content monitored by near-infrared spectroscopy) were performed for 30-min in resting state, followed by a 1-min stand-up and a 1-min sit-down period. During preprocessing, noise was filtered and the contribution of arterial blood pressure was regressed from BFV and HbT signals. Cardiorespiratory-cerebrovascular networks were reconstructed by computing pair-wise Pearson-correlation or mutual information between the resampled signals to capture their linear and/or nonlinear interdependencies, respectively. The interdependencies between cardiac, respiratory, and cerebrovascular dynamics showed a marked weakening after standing up persisting throughout the sit-down period, which could mainly be attributed to strikingly attenuated nonlinear coupling. To summarize, we found that postural changes induced topological changes in the cardiorespiratory-cerebrovascular network. The dissolution of nonlinear networks suggests that the complexity of key homeostatic mechanisms maintaining cerebral hemodynamics and oxygenation is indeed sensitive to physiological perturbations such as orthostatic stress.

In the building and construction sector, the mismatch between predicted and measured energy consumption is a well-known phenomenon called the performance gap. A promising approach to reduce the performance gap and thus improve the current building energy performance assessments are methods based on in-situ measurements. In this work, we present a building assessment process based on a novel, easily deployable wireless sensor kit. The basic sensor kit for building energy assessment presented in this study consists of a heating energy input node, several indoor temperature nodes, an outdoor temperature node, and a heat flux sensor. Specifically, the study outlines a medium-scale deployment of the sensor kit in eight occupied single-family homes in Switzerland and identifies the benefits of such an approach in the estimation of the overall heat loss coefficient and U-values. The findings of this study suggest that such sensor kits could be effectively used for rapid building performance assessment, and the paper concludes by outlining the potential benefits and implementation challenges of a larger scale study.

Resistance to toxigenic fungi and their toxins in maize is a highly important research topic, as mean global losses are estimated at about 10% of the yield. Resistance and toxin data of the hybrids are mostly not given, so farmers are not informed about the food safety risks of their grown hybrids. According to the findings aflatoxin regularly occurs at preharvest in Hungary and possibly other countries in the region can be jeopardized. We tested, with an improved methodology (two isolates, three pathogens, and a toxin control), 18 commercial hybrids (2017–2020) for kernel resistance (%), and for toxin contamination separately by two–two isolates of F. graminearum, F. verticillioides (mg/kg), and A. flavus (μg/kg). The preharvest toxin contamination was measured in the controls. Highly significant kernel resistance and toxin content differences were identified between hybrids to the different fungi. Extreme high toxin production was found for each toxic species. Only about 10–15% of the hybrids showed higher resistance to the fungal species tested and lower contamination level of their toxins. The lacking correlations between resistance to different fungi and toxins suggest that resistance to different fungi and response to toxin contamination inherits independently, so a toxin analysis is necessary. For safety risk estimation, separated artificial and natural kernel infection and toxin data are needed against all pathogens. Higher resistance to A. flavus and F. verticillioides stabilizes or improves feed safety in hot and dry summers, balancing the harmful effect of climate changes. Resistance and toxin tests during variety registration is an utmost necessity. The exclusion of susceptible or highly susceptible hybrids from commercial production results in reduced toxin contamination.

Decision making requires integrating knowledge gathered from personal experiences with advice from others. The neural underpinnings of the process of arbitrating between information sources has not been fully elucidated. In this study, we formalized arbitration as the relative precision of predictions, afforded by each learning system, using hierarchical Bayesian modeling. In a probabilistic learning task, participants predicted the outcome of a lottery using recommendations from a more informed advisor and/or self-sampled outcomes. Decision confidence, as measured by the number of points participants wagered on their predictions, varied with our definition of arbitration as a ratio of precisions. Functional neuroimaging demonstrated that arbitration signals were independent of decision confidence and involved modality-specific brain regions. Arbitrating in favor of self-gathered information activated the dorsolateral prefrontal cortex and the midbrain, whereas arbitrating in favor of social information engaged the ventromedial prefrontal cortex and the amygdala. These findings indicate that relative precision captures arbitration between social and individual learning systems at both behavioral and neural levels.

This dataset contains bibliography information regarding thermal comfort and building control research. In addition, the instruction of a data-driven literature survey method guides readers to reproduce their own literature survey on related bibliography datasets. Based on specific search terms, all relevant bibliographic datasets are downloaded. We explain the keyword co-occurrences of historical developments and recent trends, and the citation network which represents the interaction between thermal comfort and building control research. Results and discussions are described in the research article entitled “Comprehensive analysis of the relationship between thermal comfort and building control research – A data-driven literature review” (Park and Nagy, 2018).

Introduction. the conditions in the operating room can have an influence on the postoperative results of the refractive surgeryperformed with excimer lasers.Aim. the aim of this study was to examine the relationship of the temperature of pmmA plates (polymethylmethacrylate),environmental conditions and the energy load caused by the laser impulses during refractive surgery procedure.Material and methods. Wavelight Allegretto and schwind Amaris excimer lasers were used for the study. polymethylmethacrylate (pmmA) plates with parameters: -10 dpt myopic ablation and 6.5 mm optical zone were used as a target for photoablation during the calibration of excimer lasers. energy load and temperature rise were measured with high accuracy infraredthermometer.Results. logarithmically rising temperature was measured for both lasers. maximal temperature measuredwas 48°C for theAllegretto laser and 43°C for the Amaris laser.Conclusions. higher energy load with smaller repetition rate causes higher thermal load. thermal load of the pmmA plateduring the ablation is dependent on the environmental conditions, such as temperature, humidity, air flow, smoke plume evacuation, etc.

The immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor G6b-B is critical for platelet production and activation. Loss of G6b-B results in severe macrothrombocytopenia, myelofibrosis and aberrant platelet function in mice and humans. Using a combination of immunohistochemistry, affinity chromatography and proteomics, we identified the extracellular matrix heparan sulfate (HS) proteoglycan perlecan as a G6b-B binding partner. Subsequent in vitro biochemical studies and a cell-based genetic screen demonstrated that the interaction is specifically mediated by the HS chains of perlecan. Biophysical analysis revealed that heparin forms a high-affinity complex with G6b-B and mediates dimerization. Using platelets from humans and genetically modified mice, we demonstrate that binding of G6b-B to HS and multivalent heparin inhibits platelet and megakaryocyte function by inducing downstream signaling via the tyrosine phosphatases Shp1 and Shp2. Our findings provide novel insights into how G6b-B is regulated and contribute to our understanding of the interaction of megakaryocytes and platelets with glycans.

Climatic variables not only directly affect the interannual variability (IAV) in net ecosystem exchange of CO2 (NEE) but also indirectly drive it by changing the physiological parameters. Identifying these direct and indirect paths can reveal the underlying mechanisms of carbon (C) dynamics. In this study, we applied a path analysis using flux data from 65 sites to quantify the direct and indirect climatic effects on IAV in NEE and to evaluate the potential relationships among the climatic variables and physiological parameters that represent physiology and phenology of ecosystems. We found that the maximum photosynthetic rate was the most important factor for the IAV in gross primary productivity (GPP), which was mainly induced by the variation in vapour pressure deficit. For ecosystem respiration (RE), the most important drivers were GPP and the reference respiratory rate. The biome type regulated the direct and indirect paths, with distinctive differences between forests and non-forests, evergreen needleleaf forests and deciduous broadleaf forests, and between grasslands and croplands. Different paths were also found among wet, moist and dry ecosystems. However, the climatic variables can only partly explain the IAV in physiological parameters, suggesting that the latter may also result from other biotic and disturbance factors. In addition, the climatic variables related to NEE were not necessarily the same as those related to GPP and RE, indicating the emerging difficulty encountered when studying the IAV in NEE. Overall, our results highlight the contribution of certain physiological parameters to the IAV in C fluxes and the importance of biome type and multi-year water conditions, which should receive more attention in future experimental and modelling research.

The Adaptive Solar Facade (ASF) is a modular, highly integrated dynamic building facade.The energetic behavior as well as the architectural expression of the facade can be controlled with high spatio-temporal resolution through individually addressable modules. We present the general design process, the current mechanical design, and simulation results on photovoltaic power production and building energy consumption. We introduce the controller concept and show results on solar tracking as well as user interaction. Lastly, we present our current and planned prototypes.

Fluctuations in resting-state cerebral hemodynamics show scale-free behavior over two distinct scaling ranges. Changes in such bimodal (multi) fractal pattern give insight to altered cerebrovascular or neural function. Our main goal was to assess the distribution of local scale-free properties characterizing cerebral hemodynamics and to disentangle the influence of aging on these multifractal parameters. To this end, we obtained extended resting-state records (N = 214) of oxyhemoglobin (HbO), deoxyhemoglobin (HbR) and total hemoglobin (HbT) concentration time series with continuous-wave near-infrared spectroscopy technology from the brain cortex. 52 healthy volunteers were enrolled in this study: 24 young (30.6 ± 8.2 years), and 28 elderly (60.5 ± 12.0 years) subjects. Using screening tests on power-law, multifractal noise, and shuffled data sets we evaluated the presence of true multifractal hemodynamics reflecting long-range correlation (LRC). Subsequently, scaling-range adaptive bimodal signal summation conversion (SSC) was performed based on standard deviation (σ) of signal windows across a range of temporal scales (s). Building on moments of different order (q) of the measure, σ(s), multifractal SSC yielded generalized Hurst exponent function, H(q), and singularity spectrum, D(h) separately for a fast and slow component (the latter dominating the highest temporal scales). Parameters were calculated reflecting the estimated measure at s = N (focus), degree of LRC [Hurst exponent, H(2) and maximal Hölder exponent, hmax] and measuring strength of multifractality [full-width-half-maximum of D(h) and ΔH15 = H(−15)−H(15)]. Correlation-based signal improvement (CBSI) enhanced our signal in terms of interpreting changes due to neural activity or local/systemic hemodynamic influences. We characterized the HbO-HbR relationship with the aid of fractal scale-wise correlation coefficient, rσ(s) and SSC-based multifractal covariance analysis. In the majority of subjects, cerebral hemodynamic fluctuations proved bimodal multifractal. In case of slow component of raw HbT, hmax, and Ĥ(2) were lower in the young group explained by a significantly increased rσ(s) among elderly at high temporal scales. Regarding the fast component of CBSI-pretreated HbT and that of HbO-HbR covariance, hmax, and focus were decreased in the elderly group. These observations suggest an attenuation of neurovascular coupling reflected by a decreased autocorrelation of the neuronal component concomitant with an accompanying increased autocorrelation of the non-neuronal component in the elderly group.

Physiological processes—such as, the brain's resting-state electrical activity or hemodynamic fluctuations—exhibit scale-free temporal structuring. However, impacts common in biological systems such as, noise, multiple signal generators, or filtering by transport function, result in multimodal scaling that cannot be reliably assessed by standard analytical tools that assume unimodal scaling. Here, we present two methods to identify breakpoints or crossovers in multimodal multifractal scaling functions. These methods incorporate the robust iterative fitting approach of the focus-based multifractal formalism (FMF). The first approach (moment-wise scaling range adaptivity) allows for a breakpoint-based adaptive treatment that analyzes segregated scale-invariant ranges. The second method (scaling function decomposition method, SFD) is a crossover-based design aimed at decomposing signal constituents from multimodal scaling functions resulting from signal addition or co-sampling, such as, contamination by uncorrelated fractals. We demonstrated that these methods could handle multimodal, mono- or multifractal, and exact or empirical signals alike. Their precision was numerically characterized on ideal signals, and a robust performance was demonstrated on exemplary empirical signals capturing resting-state brain dynamics by near infrared spectroscopy (NIRS), electroencephalography (EEG), and blood oxygen level-dependent functional magnetic resonance imaging (fMRI-BOLD). The NIRS and fMRI-BOLD low-frequency fluctuations were dominated by a multifractal component over an underlying biologically relevant random noise, thus forming a bimodal signal. The crossover between the EEG signal components was found at the boundary between the δ and θ bands, suggesting an independent generator for the multifractal δ rhythm. The robust implementation of the SFD method should be regarded as essential in the seamless processing of large volumes of bimodal fMRI-BOLD imaging data for the topology of multifractal metrics free of the masking effect of the underlying random noise.

In magnetic resonance imaging, precise measurements of longitudinal relaxation time (T1) is crucial to acquire useful information that is applicable to numerous clinical and neuroscience applications. In this work, we investigated the precision of T1 relaxation time as measured using the variable flip angle method with emphasis on the noise propagated from radiofrequency transmit field (B1+) measurements. The analytical solution for T1 precision was derived by standard error propagation methods incorporating the noise from the three input sources: two spoiled gradient echo (SPGR) images and a B1+ map. Repeated in vivo experiments were performed to estimate the total variance in T1 maps and we compared these experimentally obtained values with the theoretical predictions to validate the established theoretical framework. Both the analytical and experimental results showed that variance in the B1+ map propagated comparable noise levels into the T1 maps as either of the two SPGR images. Improving precision of the B1+ measurements significantly reduced the variance in the estimated T1 map. The variance estimated from the repeatedly measured in vivoT1 maps agreed well with the theoretically-calculated variance in T1 estimates, thus validating the analytical framework for realistic in vivo experiments. We concluded that for T1 mapping experiments, the error propagated from the B1+ map must be considered. Optimizing the SPGR signals while neglecting to improve the precision of the B1+ map may result in grossly overestimating the precision of the estimated T1 values.

MAIN OBJECTIVES:Executive functions are frequently a weakness in children born preterm. We examined associations of executive functions and general cognitive abilities with brain structure in preterm born adolescents who were born with appropriate weight for gestational age and who have no radiological signs of preterm brain injury on neuroimaging. METHODS:The Stockholm Neonatal Project (SNP) is a longitudinal, population-based study of children born preterm (

Multi-echo fMRI data acquisition has been widely investigated and suggested to optimize sensitivity for detecting the BOLD signal. Several methods have also been proposed for the combination of data with different echo times. The aim of the present study was to investigate how these advance echo combination methods provide advantages over the simple averaging of echoes when state-of-the-art group-level random-effect analyses are performed. Both resting-state and task-based dual-echo fMRI data were collected from 27 healthy adult individuals (14 male, mean age = 25.75 years) using standard echo-planar acquisition methods at 3T. Both resting-state and task-based data were subjected to a standard image pre-processing pipeline. Subsequently the two echoes were combined as a weighted average, using four different strategies for calculating the weights: (1) simple arithmetic averaging, (2) BOLD sensitivity weighting, (3) temporal-signal-to-noise ratio weighting and (4) temporal BOLD sensitivity weighting. Our results clearly show that the simple averaging of data with the different echoes is sufficient. Advanced echo combination methods may provide advantages on a single-subject level but when considering random-effects group level statistics they provide no benefit regarding sensitivity (i.e. group-level t-values) compared to the simple echo-averaging approach. One possible reason for the lack of clear advantages may be that apart from increasing the average BOLD sensitivity at the single-subject level, the advanced weighted averaging methods also inflate the inter-subject variance. As the echo combination methods provide very similar results, the recommendation is to choose between them depending on the availability of time for collecting additional resting-state data or whether subject-level or group-level analyses are planned.

Preterm birth has been shown to induce an altered developmental trajectory of brain structure and function. With the aid support vector machine (SVM) classification methods we aimed to investigate whether MRI data, collected in adolescence, could be used to predict whether an individual had been born preterm or at term. To this end we collected T1-weighted anatomical MRI data from 143 individuals (69 controls, mean age 14.6y). The inclusion criteria for those born preterm were birth weight ≤ 1500g and gestational age < 37w. A linear SVM was trained on the grey matter segment of MR images in two different ways. First, all the individuals were used for training and classification was performed by the leave-one-out method, yielding 93% correct classification (sensitivity = 0.905, specificity = 0.942). Separately, a random half of the available data were used for training twice and each time the other, unseen, half of the data was classified, resulting 86% and 91% accurate classifications. Both gestational age (R = -0.24, p

On 19th June 2001, the Hungarian Parliament adopted an Act on “Hungarians living in neighboring countries” or the so-called “Status Law”. It came into force on 1st January 2002, giving special rights to Hungarian minority living in neighboring countries. This step was taken in order to exempt Hungarians living in Romania, Ukraine, Slovakia, Yugoslavia and Croatia from visa requirements for non-Schengen countries in the case of EU enlargement. The law raised controversy in the aforementioned neighboring countries and in EU itself, because it was adopted by the Hungarian Parliament without consultation with the EU Council, a matter made worse by the fact that some of the provisions laid down in this law are apparently in conflict with the prevailing European standards on minority protection. The present article concentrates on the peculiarities of migration processes in Hungary, whilst analyzing Hungarian migration policy (the so-called ethnic approach) and discussing the consequences of Status Law implementation. Hungary is becoming more and more Western in its migration and demographic pattern. Like other Western countries it is faced with a lack of labor force and is trying to find its own solution to this problem, even to the extent of acting against EU regulations and international legal norms. The migration policy of the country is determined by the national policy for maintenance of close relations with Hungarians in neighboring countries, where a significant number of Hungarians live. The implementation of this law will help Hungarians (in the Hungarian government’s opinion) to restrict emigration from one side, and will simultaneously moderate the process of assimilation of Hungarians into these neighboring countries as well. However, analysis of the migration history of Hungary over the last decade shows that this statement is very doubtful. In reality, the well-organized financial provisions, which are provided by the Status Law for almost all spheres of life for Hungarians living in neighboring countries, will lead to emigration of Hungarians to their motherland.

Brodmann's 100-year-old summary map has been widely used for cortical localization in neuroscience. There is a pressing need to update this map using non-invasive, high-resolution and reproducible data, in a way that captures individual variability. We demonstrate here that standard HARDI data has sufficiently diverse directional variation among grey matter regions to inform parcellation into distinct functional regions, and that this variation is reproducible across scans. This characterization of the signal variation as non-random and reproducible is the critical condition for successful cortical parcellation using HARDI data. This paper is a first step towards an individual cortex-wide map of grey matter microstructure, The gray/white matter and pial boundaries were identified on the high-resolution structural MRI images. Two HARDI data sets were collected from each individual and aligned with the corresponding structural image. At each vertex point on the surface tessellation, the diffusion-weighted signal was extracted from each image in the HARDI data set at a point, half way between gray/white matter and pial boundaries. We then derived several features of the HARDI profile with respect to the local cortical normal direction, as well as several fully orientationally invariant features. These features were taken as a fingerprint of the underlying grey matter tissue, and used to distinguish separate cortical areas. A support-vector machine classifier, trained on three distinct areas in repeat 1 achieved 80-82% correct classification of the same three areas in the unseen data from repeat 2 in three volunteers. Though gray matter anisotropy has been mostly overlooked hitherto, this approach may eventually form the foundation of a new cortical parcellation method in living humans. Our approach allows for further studies on the consistency of HARDI based parcellation across subjects and comparison with independent microstructural measures such as ex-vivo histology.

Regulator of G-protein signaling 18 (RGS18) is a GTPase-activating protein that turns off Gq signaling in platelets. RGS18 is regulated by binding to the adaptor protein 14-3-3 via phosphorylated serine residues S49 and S218 on RGS18. In this study we confirm that thrombin, thromboxane A2, or ADP stimulate the interaction of RGS18 and 14-3-3 by increasing the phosphorylation of S49. Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. To understand the effect of S216 phosphorylation we studied the phosphorylation kinetics of S49, S216, and S218 using Phos-tag gels and phosphorylation site-specific antibodies in transfected cells and in platelets. Cyclic nucleotide-induced detachment of 14-3-3 from RGS18 coincides initially with double phosphorylation of S216 and S218. This is followed by dephosphorylation of S49 and S218. Dephosphorylation of S49 and S218 might be mediated by protein phosphatase 1 (PP1) which is linked to RGS18 by the regulatory subunit PPP1R9B (spinophilin). We conclude that PKA and PKG induced S216 phosphorylation triggers the dephosphorylation of the 14-3-3 binding sites of RGS18 in platelets.

Traumatic spinal cord injury (SCI) leads to disruption of axons and macroscopic tissue loss. Using diffusion tensor imaging (DTI), we assessed degeneration of the corticospinal tract (CST) in the cervical cord above a traumatic lesion and explored its relationship with cervical atrophy, remote axonal changes within the cranial CST and upper limb function.Nine cervical injured volunteers with bilateral motor and sensory impairment and ten controls were studied. DTI of the cervical cord and brain provided measurements of fractional anisotropy (FA), while anatomical MRI assessed cross-sectional spinal cord area (i.e. cord atrophy). Spinal and central regions of interest (ROI) included the bilateral CST in the cervical cord and brain. Regression analysis identified correlations between spinal FA and cranial FA in the CST and disability.In individuals with SCI, FA was significantly lower in both CSTs throughout the cervical cord and brain when compared with controls (p≤0.05). Reduced FA of the cervical cord in patients with SCI was associated with smaller cord area (p = 0.002) and a lower FA of the cranial CST at the internal capsule level (p = 0.001). Lower FA in the cervical CST also correlated with impaired upper limb function, independent of cord area (p = 0.03).Axonal degeneration of the CST in the atrophic cervical cord, proximal to the site of injury, parallels cranial CST degeneration and is associated with disability. This DTI protocol can be used in longitudinal assessment of microstructural changes immediately following injury and may be utilised to predict progression and monitor interventions aimed at promoting spinal cord repair.

In the photosynthetically most active spring, summer and autumn vege­ tation period the investigated grassland did maintain a relatively strong daytime carbon gain. During winter the grassland displayed a slight daytime carbon loss. These data suggest that the grassland was a weak sink for carbon in the investigated period. CO2 exchange variability during the day seemed to be independent from that of the daily photosynthetic radiation. Thus other factors like soil respiration, soil moisture content and temperature and their interactions could be responsible for the high daily variabil­ ity of grassland CO2-exchange. The considerable temporal (daily and seasonal) vari­ ability of the grassland CO2-exchange can be considered as a characteristic feature of the grassland CO2-exchange. In the investigated loess grassland vegetation the variabil­ ity of CO2-exchange showed clear dependence on measuring area, which is obvious in the CV of NEE. We hypothetised that the spatial scale with the lowest variability is the characteristic area of the grassland ecosystem's CO2-exchange (CO2-exchange physi­ ological unit). In general decreased variability indicates a more regulated state.

Parallel coenological and synphysiological examinations were carried out on three typical xerophilous loess grassland stands of Salvio-Festucetum rupicolae community in the Gödöllö Hills, near Isaszeg village. Three stand types, a Carex humilis, a Chamaecytisus austriacus and a Stipa dasiphylla dominated ones were investigated at the same spatial scale (mesoscale). In our sample area apparent dominance by three species (Festuca rupicola, Stipa dasiphylla, and Carex humilis) suggested that these stands of this subassociation have been emerged from three types of differing species composition. According to these analyses three groups dominated by Carex humilis, Chamaecytisus austriacus and Stipa dasiphylla of festucetosum rupicolae subassociation of a stand of Salvio-Festucetum rupicolae association were separated. Results of the synphysiological measurements show, that water shortage and senescence in autumn are responsible for the different physiological performances of the three types. In the well-watered summer period we found significant difference only between the physiological activity of the Carex- and Chamaecytisus- dominated types, however this difference is due to the significant LAI-difference and after relating photosynthesis to 1 m2 leaf area, the difference is non-significant.

Chlorophylls and carotenoid pigments were investigated in leaves of beet (Beta vulgaris L.) obtained from SDE Cluj-Napoca, harvested in September 1987. Leaves had a higher content both in chlorophylls and carotenoids than petioles. The high content in chlorophyll b and B-carotene is of great importance. The chlorophyll a and chlorophyll b ratio was of 1,8 in leaves and 1,36 in petioles respectively. The main carotenoids in leaves are lutheine and B-carotene, followed by violaxanthine, criptixanthins, zeaxanthine and neoxanthine in decreasing order of their content. Carotenoids with provitaminic structure represent 41,4% of the total carotenoid content in leaves and 38% in petioles. As characteristic aspects can be mentioned the proximate content of lutheine and B-carotine (2:1); the prevailence of carotenoids with B-iononic structure, and the high content of oxygenate carotenoids. Due to the high content of chlorophylls and carotenoids, the high biomass yield, Beta vulgaris L. seems suitable for industrial production of chlorophylls and carotenoids which possess a large scale of utilization.

Within the framework of chemotaxonomical investigations in higher plants, we carried on further researches on carotenoid pigments in some yet unstudied species of the genus Cucumis.

Im Rahmen unserer chemotaxonomischen Untersuchungen uber die Carotinoide hoherer Pflanzen (1, 2, 3, 4, 5) befassen wir uns in vorliegender Arbeit mit den Carotinoiden einiger Pflanzen der Gattung Cucurbita. Wir berichten von C. maxima Duch. var. bananina Greb., C. maxima Duch. var. maxima cv. Marica, C. pepo var. oblonga Greb. und C. pepo var. pyriformis Alef., unter Hinweis auf carotenotaxonomisch interessante Befunde.

Interannual variability (IAV, represented by standard deviation) in net ecosystem exchange of CO2 (NEE) is mainly driven by climatic drivers and biotic variations (i.e., the changes in photosynthetic and respiratory responses to climate), the effects of which are referred to as climatic (CE) and biotic effects (BE), respectively. Evaluating the relative contributions of CE and BE to the IAV in carbon (C) fluxes and understanding their controlling mechanisms are critical in projecting ecosystem changes in the future climate. In this study, we applied statistical methods with flux data from 65 sites located in the Northern Hemisphere to address this issue. Our results showed that the relative contribution of BE (CnBE) and CE (CnCE) to the IAV in NEE was 57%±14% and 43%±14%, respectively. The discrepancy in the CnBE among sites could be largely explained by water balance index (WBI). Across water-stressed ecosystems, the CnBE decreased with increasing aridity (slope=0.18%mm−1). In addition, the CnBE tended to increase and the uncertainty reduced as timespan of available data increased from 5 to 15 years. Inter-site variation of the IAV in NEE mainly resulted from the IAV in BE (72%) compared to that in CE (37%). Interestingly, positive correlations between BE and CE occurred in grasslands and dry ecosystems (r>0.45, P