Elevated immunoglobulin E (IgE) levels are commonly associated with allergies. However, high IgE levels are also found in several other infectious and non-infectious disorders. Elevated IgE levels typically suggest allergies, eczema, or recurrent skin infections. Very high IgE levels are uncommon in patients with active eczema but typically reflect a monogenic atopic condition or inborn immune defects with an atopic phenotype. The aim of our research is to identify if the possible cause of high IgE levels is also dependent on external factors, age, or associated recurrent pathologies such as infections. To answer this question, we performed a one-year retrospective study that included 200 hospitalized children who had at least two viral or bacterial infections in the six months preceding hospitalization. Measurements of IgE and allergen panels (respiratory and digestive) using blood samples revealed that individuals who tested positive for the body’s synthesis of hyperimmunoglobulin E were not observably allergic to any potential allergens despite having higher total serum IgE. According to the results, there was a strong correlation between elevated IgE serum levels and a history of infectious diseases among the patients.

Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc N-glycosylation patterns that can affect the allergic reaction to food in multiple ways. High affinity IgE is required to induce strong mast cell activation eventually leading to allergic anaphylaxis while low affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgA and IgG antibodies can inhibit IgE-mediated mast cell activation through various mechanisms, thereby protecting IgE-positive individuals from allergy development. The production of IgE and IgG with differential allergenic potential seems to be affected by the signaling strength of individual B cell receptors, and by cytokines from T cells. This review provides an overview of the diversity of the B cell response and the diverse roles of antibodies in food allergy.

This paper deals with developing a new class of quaternions, called hyper-dual Horadam quaternions which are constructed from the quaternions whose components are hyper-dual Horadam numbers. We investigate the algebraic properties of these quaternions.

Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Experimentally, sensitization with alum adjuvant favors IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying TLR-regulation of immunoglobulin production are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. We show that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited when sensitization to OVA was performed in the presence of CpG. Notably, CpG-mediated suppression of IgE production required MyD88-expression on DCs but not on B-cells. This contrasts with previous reports of in vitro regulation IgE where CpG acted directly on B cells via MyD88 pathway. In addition, CpG also inhibited IgE production in a MyD88-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signaling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.

To increase the prediction accuracy of positive oral food challenge (OFC) outcome during stepwise slow oral immunotherapy (SS-OIT) in children with hen’s egg (HE) allergy, we evaluated the predictive value of the combination of antigen-specific IgE (sIgE) with antigen binding-avidity and sIgG4 values. Sixty-three children with HE allergy undergoing SS-OIT were subjected to repeated OFC with HE. We measured the ovomucoid (OVM)-sIgE by ImmunoCAP or densely carboxylated protein (DCP) microarray, sIgG4 by DCP microarray, and the binding-avidity of OVM-sIgE defined as the level of 1/ IC50 (nM) measured by competitive binding inhibition assays. The OFC was positive in 37 (59%) patients undergoing SS-OIT. Significant differences in DCP-OVM-sIgE, CAP-OVM-sIgE, I/ IC50, DCP-OVM-sIgG4, the multiplication products of DCP-OVM-sIgE and binding-avidity of DCP-OVM-sIgE (DCP-OVM-sIgE/IC50) and DCP-OVM-sIgE/sIgG4 were compared between the negative and positive groups (p<0.01). Among them, the variable with greatest area under the receiver operating characteristic curve was DCP-OVM-sIgE/IC50 (0.84), followed by DCP-OVM-sIgE/sIgG4 (0.81). DCP-OVM-sIgE/IC50 and DCP-OVM-sIgE/sIgG4 are potentially useful markers for the prediction of positive OFC during HE-SS-OIT and may allow proper evaluation of the current allergic status in the healing process during HE-SS-OIT

We examine the extensions of the basic arithmetical operations of addition and multiplication on the natural numbers into higher-rank hyper-operations also on the natural numbers. We go on to define the concepts of prime and composite numbers under these hyper-operations and derive some results about factorisation, resulting in fundamental theorems analogous to the Fundamental Theorem of Arithmetic.

(1) Background: This study aimed to evaluate the implications of IL-31 in the pathogenesis of chronic spontaneous urticaria (CSU) and to assess the differences that occur between its serum values compared to controls. Additionally, the serum IL-31 levels were measured alongside other clinical and paraclinical parameters identified in the patients to understand its immunological importance in this skin disease and to determine if it could potentially serve as a therapeutic target in CSU in the future. (2) Methods: The serum levels of IL-31 were estimated in 50 patients diagnosed with CSU according to the international guidelines. Additionally, 38 controls who had not experienced any episodes of urticaria during their lifetime were included. (3) Results: Our data have shown higher serum levels of IL-31 in CSU patients compared to controls. A correlation between the serum level of IL-31 and other inflammatory markers, such as ERS, CRP, or serum eosinophils and total IgE was not identified. On the other hand, statistically significant differences were found in IL-31 serum values in UCS patients depending on the severity of the disease, its impact on the patients' quality of life, the severity of itching, and the response to H1 antihistamines. (4) Conclusions: In the present study, IL-31 did not change directly with non-specific inflammation, nor with eosinophilic inflammation or atopy. However, its expression was modified in CSU depending on major characteristics of the disease: severity, pruritus, and response to H1 antihistamines. The focus on the pathogenesis of CSU is of indisputable significance since any additional information in understanding the mechanisms of this disease can open doors to new therapeutic targets. This is particularly important considering that the available therapies are deficient, incomplete, and the remaining symptoms are uncontrolled in many cases.

High prevalence of allergic disorders in Indian pediatric patients demands early diagnosis of allergens so that appropriate allergen avoidance methods, pharmacotherapy or immunotherapy can be provided in time to avoid the worsening of symptoms due to triggers. In this context, identification of the most prevalent aeroallergens in a given area is critical for diagnosis and treatment of various allergic reactions especially in case of rhino-conjunctivitis and asthma. The specific diagnosis of IgE mediated allergy is usually based on the correlation between the clinical history and signs and symptoms endorsed by the diagnostic tests. Skin prick tests are the gold standard however has some limitation. In view of this, the aim of this study was to assess the significance of ImmunoCAP assay for assessing serum specific IgE levels, available in India, against skin prick test by standardized allergens, for the diagnosis of allergic sensitization. A single-center observational study was conducted at tertiary care corporate hospitals in North India from 2017-2020. Patients with self-reported allergic symptoms or whose symptoms were suspected for allergies were tested for the type of sensitization using skin prick test (SPT) after their consents followed by ImmunoCAP based quantification of serum specific IgE levels. A total of 256 (95.9%) pediatric patients were analyzed in the study and were analysed. The patients were most commonly (30% patients) sensitized to D. farinae (173 [67.6%]), D. pteronyssinus (174 [68.0%]), Acarus siro (93 [36.3%]), Lepidoglyphus destructor (96 [37.5%]), Plantago lanceolata (Engl.). The ROC curve of Bermuda grass shows that the AUC of serum-specific IgE is larger than that of SPT (1.000 / 0.881). The receiver operating characteristic (ROC) analysis of serum-specific IgE reference method resulted in the largest AUC of all the allergens taken into consideration (0.711 / 1.000) compared to those of SPT (0.589 / 1.000). These results revealed that serum-specific IgE is more reliable method over prick test for accessing the sensitivity of patient for various allergens. This study may be helpful in performing early diagnosis of allergies as well as in taking appropriate preventive measures for managing life threatening allergic reactions

The prevalence of food allergy has increased in recent years, especially in children. Food allergen avoidance and symptomatic drugs in case of an allergic reaction remain the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanuts, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.

The proper hydrogenation of Hyper-coal (HPC) using 1, 2, 3, 4-tetrahydroquinoline (THQ) was able to decrease the oxygen content and adjust the molecular structure of HPC for preparing the spinnable pitch with high softening point (SP). The spinnable pitch prepared from the THQ-soluble (QS) fraction of HPC as a precursor consisted more naphthenic carbon groups than that prepared from the 1-methylnaphthalene (1-MN) soluble (MNS) fraction of HPC. The HPC-QS derived pitch showed excellent spinnability even the SP of 260°C, and the tensile strength of the resultant carbon fiber was up to 1350 MPa with a diameter around 8 µm by only heat treatment at 800°C for 5 min.

Effects of pulsed electromagnetic fields (PEMF) on immunological factors in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) model were investigated. Hairless mice were randomly assigned to control, acetone and olive oil solution-treated (AOO), PEMF 15 Hz, PEMF 75 Hz, and sham groups (n=5 each). AOO solution was used to dissolve DNCB. Both PEMF and sham groups were exposed to similar DNCB doses, causing similar AD symptoms. After AD induction for five weeks, only the PEMF group was exposed to PEMF stimulations (15 Hz, 75 Hz, and 15 mT) for two weeks inside the solenoid coil. In both groups, splenomegaly was observed, as AD was induced by hyperimmune reactions caused by DNCB sensitization. However, splenomegaly did not occur in the PEMF-exposed groups, and spleen weight decreased similarly to that of the control. Hence, the total splenocytes in the PEMF group were similar to those in the control group, whereas the sham group showed thrice the number of splenocytes compared to the PEMF group. The serum immunoglobulin E levels did not significantly change in the PEMF group; however, they increased more than fourfold in the sham group. These results demonstrate that PEMF stimulation ameliorates the abnormal symptoms caused by hyperimmune reactions.

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation and we discuss the mechanisms by which exosomes could be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: a) Mast cell derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. c) Exosomes could promote TH1-like responses towards an allergen. d) Exosomes could modulate IgE-facilitated antigen presentation.

Background: Asthma is the most common chronic disease affecting children and altering their quality of life. The severity of asthma is often modulated by immunoglobulin E (IgE)-mediated allergen sensitization and is associated with comorbid allergic dis-eases. Omalizumab is a humanized monoclonal antibody anti-IgE, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omali-zumab in Romanian paediatric patients with severe allergic asthma. Methods: In this observational real-life study, 12 children aged 6 to 18 years, (mean age 12.4 years ) with severe allergic asthma received Omalizumab as an add-on treatment. The levels of asthma control, exacerbations, lung function and adverse events were evaluated at baseline and after the first year of treatment. Results: We noticed general improvements in total asthma symptom scores and the rate of exacerbation of severe asthma. Omalizumab increased the initial variables of lung function, and no serious adverse reactions were reported. FEV1 improved statistically significant after one year of treatment with Omalizumab, [ΔFEV1 (% pred.) =18.3, and similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rates due to asthma decreased from 4.1 (2.8 SD) to 1.15 (0.78 SD) during the treatment year (p<0.0001) with Omalizumab. Conclusions: Treatment with Omalizumab can be an effective and safe therapeutic option for Romanian children with severe allergic asthma, providing clinically relevant in-formation on asthma control and exacerbation rate in children and adolescents. The results highlighted the effect of Omalizumab in young patients, starting from the first year of treatment.

The spectrums of one type of object under different conditions have the same features (up, down, protruding, concave) at the same spectral positions, which can be used as primary parameters to evaluate the difference among remotely sensed pixels. Wavelet-feature correlation ratio Markov clustering algorithm (WFCRMCA) for the remotely sensed data is proposed based on an accurate description of abrupt spectral features and an optimized Markov clustering in the wavelet feather space. The peak points can be captured and identified by applying a wavelet transform to spectral data. The correlation ratio between two samples is a statistical calculation of the matched peak point positions on the wavelet feature within an adjustable spectrum domain or a range of wavelet scales. The evenly sampled data can be used to create class centers, depending on the correlation ratio threshold at each Markov step, accelerating the clustering speed by avoiding the computation of Euclidean distance for traditional clustering algorithms, such as K-means and ISODATA. Markov clustering applies several strategies, such as a simulated annealing method and gradually shrinking the clustering size, to control the clustering convergence. At each clustering tempera-ture, it can obtain the best class centers quickly. The experimental results of the Airborne Visible/ Infrared Imaging Spectrometer (AVIRIS) and Thermal Mapping (TM) data have verified its ac-ceptable clustering accuracy and high convergence velocity.

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, though how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation; specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

Killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) was previously thought to be a human NK-cell-specific protein but its expression has also been demonstrated in human mast cells. Mast cells are involved in allergic reactions via their KIT-mediated and IgE receptor-mediated responses. We recently detected the expression of KIR2DL4 in human cultured mast cells established from peripheral blood derived from healthy volunteers (PB-mast), a human mast cell line (LAD2), and non-neoplastic mast cells, including pathological specimens. An agonistic antibody against KIR2DL4 negatively regulates the KIT- and IgE-receptor-mediated responses of PB-mast and LAD2 cells. In addition, agonistic antibodies and human leukocyte antigen (HLA)-G, a natural ligand for KIR2DL4, induce the secretion from these cells of leukemia inhibitory factor and serine proteases, which have been implicated in pregnancy establishment and cancer metastasis. Therefore, KIR2DL4 stimulation with agonistic antibodies and recombinant HLA-G protein may enhance both processes, in addition to suppressing mast-cell-mediated allergic reactions.

Objective: To determine the effect of birth season climate on adult total serum IgE (TSIgE) levels. Study design: The study is a retrospective chart review with the following inclusion criteria: TSIgE measurement, age ≥16, and northeastern Tennessee birthplace. Main outcome measures include TSIgE levels, birth season climatic conditions, and regional pollen-producing plant and pollen counts. Results: The records of 1,274 women (mean age 40.8 ± 17.5, age range 16-96) and 762 men (mean age 38.1 ± 17, age range 16-82) seen in our Allergy Clinic were reviewed. Persons born in the spring and summer, the seasons with the highest pollen counts and the most favorable climatic conditions for plant growth, had nearly twice the odds of having TSIgE levels >1σ above the mean of the study group when compared to those born in the fall or winter (odds ratio (OR) 1.75, 95% confidence interval (CI) 0.96-3.17 and OR 1.93, 95% CI 1.04-3.57, respectively); odds were highest for those born in March (OR 2.55, 95% CI 1.37-4.74) and July (OR 2.38, 95% CI 1.25-4.51) and lowest for those born in November (OR 0.11, 95% CI 0.0068-1.79). When averaged over the 95-years of study and five 30-year climate cycles TSIgE levels increased linearly as the seasons progressed from fall to summer (r²= 0.9475, P=0.0266). Of the climatic factors, TSIgE levels correlated most strongly with levels of precipitation (r²= 0.9145, P=0.0437). Conclusion: Climatic conditions that increase birth season exposure to environmental allergens may have a life-long effect on TSIgE production.

Several animal food allergens assembly into amyloids under gastric-like environments. These aggregated structures provide Gad m 1 with an enhanced IgE interaction due to the amyloid assembly of the epitope regions. However, whether these properties are unique of Gad m 1 or common to other food allergens has not yet been addressed. Using Bos d 5, Bos d 12 and Gal d 2 as food allergen models and Gad m 1 as control, aggregation reactions and the sera of milk, egg and fish allergic patients we have analyzed the IgE interaction of the distinct amyloids. We found that amyloids formed by Bos d 12 and Gal d 2 full-length and truncated chains are recognized by the IgEs of milk and egg allergic patient sera. As with Gad m 1, in most cases amyloid recognition is higher than that of the precursor structure. Bos d 5 was not recognized under any fold by the IgE of the sera studied. These results support that formation of IgE-binding amyloids might be a common feature to animal food allergen.

The first hyperpolarizability of graphene quantum dots (GQDs) suspended in water was determined using the hyper-Rayleigh scattering (HRS) technique. To the best of our knowledge, this is the first application of the HRS technique to characterize GQDs. Two commercial GQDs (Acqua-Cyan and Acqua-Green) with different compositions were studied. The HRS experiments were performed with an excitation laser at 1064 nm. The measured hyperpolarizabilities were (1.0±0.1) × 10^(-27) esu and (0.9±0.1) × 10^(-27) esu for Acqua-Cyan and Acqua-Green, respectively. The results were used to estimate the hyperpolarizability per nanosheet obtained by assuming that each GQDs has five nanosheets with 0.3 nm thickness. The two-level model, used to calculate the static hyperpolarizability per nanosheet, provides the values of (2.4±0.1) × 10^(-28) esu (Acqua-Cyan) and (0.5±0.1) × 10^(-28) esu (Aqua-Green). The origin of the nonlinearity is discussed on the basis of polarized resolved HRS experiments, and an electric quadrupolar behavior with a strong dependence on surface effects is found. The nontoxic characteristics and order of magnitude indicate that these GQDs may be useful for biological microscopy imaging.

We have particularly investigated the correlation law of the effect of different carbon black fillings on the hyper-elastic mechanical behavior of natural rubber by conducting uniaxial tensile tests over a wide range of deformations with different volume fractions of carbon black fillings (0%, 4.7%, 8.9%, 12.8%, 16.4%, 19.7%, 22.7%, 25.2%). The results show that the stress-strain curve for carbon black filled rubber increases with the amount of filling, meaning that the rubber gradually becomes "harder". We explore the correlation between the carbon black filling volume and the parameters of the Yeoh constitutive model by examining the Yeoh constitutive model to characterize the hyper-elastic mechanical behavior of rubber with different carbon black fillings. A quantitative relationship between the material parameters and the carbon black filling volume in the Yeoh constitutive model is presented. A method for calculating the material parameters of the Yeoh constitutive model is developed and it predicts the correlation between the hyper-elastic properties of rubber and the volume fraction of carbon black filling.

A wealth of Full Waveform (FW) LiDAR data are available to the public from different sources, which is poised to boost the extensive application of FW LiDAR data. However, we lack a handy and open source tool that can be used by potential users for processing and analyzing FW LiDAR data. To this end, we introduce waveformlidar, an R package dedicated to FW LiDAR processing, analysis and visualization as a solution to the constraint. Specifically, this package provides several commonly used waveform processing methods such as Gaussian, adaptive Gaussian and Weibull decompositions, and deconvolution approaches (Gold and Richard-Lucy (RL)) with users’ customized settings. In addition, we also developed functions to derive commonly used waveform metrics for characterizing vegetation structure. Moreover, a new way to directly visualize FW LiDAR data is developed through converting waveforms into points to form the Hyper Point cloud (HPC), which can be easily adopted and subsequently analyzed with existing discrete-return LiDAR processing tools such as LAStools and FUSION. Basic explorations of the HPC such as 3D voxelization of the HPC and conversion from original waveforms to composite waveforms are also available in this package. All of these functions are developed based on small-footprint FW LiDAR data, but they can be easily transplanted to the large footprint FW LiDAR data such as Geoscience Laser Altimeter System (GLAS) and Global Ecosystem Dynamics Investigation (GEDI) data analysis. It is anticipated that these functions will facilitate the widespread use of FW LiDAR and be beneficial for better estimating biomass and characterizing vegetation structure at various scales. The package and code examples can be found at https://github.com/tankwin08/waveformlidar.

The hyper-arid environment is characterized by high inter-annual climatic fluctuations. The yearly average rainfall can change substantially for several years, forming wet or dry sub-periods. Observing rainfall trends over a sub-period can lead to a false perception of a change in the trend but may in fact represent a periodic cycle when examined on a larger time scale. We aimed to better characterize the rainfall regime prevailing in the hyper-arid Arava Valley (Israel/Jordan), and to examine the response of vegetation to annual rainfall. We hypothesized that annual and perennial vegetation would respond differently to wet and dry sub-periods, and that grazing activities will impact vegetation growth. We used a time series of monthly rainfall, from which we calculated Standard Precipitation Index (SPI), and calculated proxies of perennial and annual vegetation over the last four decades using Landsat-derived Normalized Difference Vegetation Index (NDVI). We found no clear trend in rainfall amounts during this period, however we did identify wet and dry sub-periods which were statistically distinct in rain and in vegetation patterns from each other. The highest levels of correlation between rainfall and the NDVI derived proxies were found when examining average rainfall over a period of two- three years for the annual vegetation and over four years for perennial vegetation. Using the Mann-Kendall test, we identified a time lag of two to four years, with the proxies of annual vegetation responding faster than the proxies of perennial vegetation, to shifts between wet and dry sub-period. In addition, we found a consistent difference between natural vegetation cover in Jordan (grazed) and Israel (non-grazed), favoring the development of natural vegetation on the Israeli side. We conclude that integrating between long-term remote sensing satellite imagery and climatic records revealed the greater resilience of perennial vegetation in the hyper-arid region to climatic fluctuation, and enabled us to identify the vegetation’s sensitivity to anthropogenic impact.

The expansion of copper mining on the hyper-arid pacific slope of southern Peru has precipitated growing concern for scarce water resources in the region. Located in the headwaters of the Torata river, in the department of Moquegua, the Cuajone mine, owned by Southern Copper, provides a unique opportunity, in a little-studied region, to examine the relative impact of the landscape-scale mining on water resources in the region. Principal component analysis and cluster analysis of the water chemistry data from 16 sites, collected over three seasons during 2017 and 2018, show distinct statistical groupings indicating that, above the settlement of Torata, water geochemistry is a function of chemical weathering processes acting upon underlying geological units, and confirming that the Cuajone mine does not significantly affect water quality in the Torata river. Impact mitigation strategies that firstly divert channel flow around the mine and secondly divert mine waste to the Toquepala river and tailings dam at Quebrada Honda, below the Toquepala mine, in the department of Tacna, secure water quality in the Torata river for the foreseeable future. In the greater Moquegua river catchment, our results further suggest that water quality has been more significantly impacted by urban effluents and agricultural runoff than the Cuajone mine. The increase in total dissolved solids in the waters of the lower catchment reflects the cumulative addition of dissolved ions through chemical weathering of the underlying geological units, supplemented by rapid recharge of surface waters contaminated by residues associated with agricultural and urban runoff through the porous alluvial aquifer. Concentrations in some of the major ions exceeded internationally recommended maxima for agricultural use, especially in the coastal region. Occasionally, arsenic and manganese contamination also reached unsafe levels for domestic consumption. In the lower catchment, below the Cuajone mine, data and multivariate analyses point to urban effluents and agricultural run-off rather than weathering of exposed rock units, natural or otherwise, as the main cause of contamination.

This paper describes and demonstrates an autonomous robotic team that can rapidly learn the characteristics of environments that it has never seen before. The flexible paradigm is easily scalable to multi-robot, multi-sensor autonomous teams, and is relevant to satellite calibration/validation and the creation of new remote sensing data products. A case study is described for the rapid characterisation of the aquatic environment, over a period of just a few minutes we acquired thousands of training data points. This training data allowed our machine learning algorithms to rapidly learn by example and provide wide area maps of the composition of the environment. Along side these larger autonomous robots two smaller robots that can be deployed by a single individual were also deployed (a walking robot and a robotic hover-board), observing significant small scale spatial variability.

Hypergravity accelerators are a type of large machinery used for gravity training or medical research. A failure of such large equipment can be a serious problem in terms of safety or costs. This paper proposes a prediction model that can proactively prevent failures that may occur in a hy-pergravity accelerator. The method proposed in this paper was to convert vibration signals to spectograms and perform classification training using a deep learning model. An experiment was conducted to evaluate the performance of the method proposed in this paper. A 4-channel accel-erometer was attached to the bearing housing, which is a rotor, and time-amplitude data were obtained from the measured values by sampling. The data were converted to a two-dimensional spectrogram, and classification training was performed using a deep learning model for four conditions of the equipment: Unbalance, Misalignment, Shaft Rubbing, and Normal. The ex-perimental results showed that the proposed method had a 99.5% F1-Score, which was up to 23% higher than the 76.25% for existing feature-based learning models.

Background: Little is known about the natural history of immunoglobulin (Ig) E-mediated diseases in preterm infants, further hampered by the lack of noninvasive investigations. We aimed at developing a non-invasive tool for the study of IgE and eosinophil-derived neurotoxin (EDN) in neonatal fecal samples and evaluating its predictive value for the development of IgE-mediated diseases (cow’s milk allergy, asthma, or atopic dermatitis) during the first year of life. Methods: We developed a stool extraction protocol, followed by freeze-drying and solubilization. sIgE responses were investigated in neonatal fecal samples from 21 preterm infants with a 300-allergen multiplex containing whole and molecular allergens and confirmed by capillary Western blot with nano-immunoassay. The local eosinophilic component was investigated by measuring the concentration of EDN. Results: The multiplexed allergen assay detected sIgE in all samples. Confirmation was obtained with Western blot. Frequency and levels of sIgE in neonatal fecal samples differed between infants who developed IgE-mediated diseases and controls. Neonatal fecal sIgE directed to milk proteins predicted later development of cow’s milk allergy (specificity 88%, sensitivity 78%). Allergen specificity of neonatal fecal sIgE was associated with later development of cow’s milk allergy and asthma. Neonatal fecal EDN levels predicted the development of IgE-mediated diseases (sensitivity 100%, specificity 75%). Conclusion: Non-invasive investigation of neonatal fecal sIgE is a promising tool for the prediction of subsequent development of IgE-mediated diseases.

The identification of bloodstain is one of the most important approaches in obtaining evidence in criminalistics. A threshold method based on spectral co-efficient and interclass variance is proposed in this paper, it is a non-contact, non-destructive method for quickly identifying bloodstains. The spectra of bloodstains and other suspected substances were all extracted from their hyper-spectral image. Then calculate the correlation coefficients of these spectral and interclass variances, analyze the differences between substances. The best blood recognition threshold was determined as 0.9. After preprocessing for eliminating systematic errors, experiments with the threshold 0.9 are carried out to identify bloodstains on the calico and red T-shirt. The method can remarkably identify the bloodstain from other non-blood substances both quickly and efficiently. The blood extraction rate can reach to 93.35% and 89.19%, respectively. It is an important step toward the implementation of bloodstain non-contact and non-destructive identification in forensic casework.

Studies of mast cell biology is dependent on relevant and validated in vitro models. We here present detailed information concerning the phenotype of both freshly isolated human skin mast cells (MCs), and of in vitro cultures of these cells that was obtained by analyzing their total transcriptome. Transcript levels of MC-related granule proteins and transcription factors were found to be remarkably stable over a 3-week culture period. Relatively modest changes were also seen for important cell surface receptors including the high affinity receptor for IgE, FCER1A, the low affinity receptor for IgG, FCGR2A, and the receptor for stem cell factor, KIT. FCGR2A was the only Fc receptor for IgG expressed by these cells. Comparisons of the present transcriptome against previously reported transcriptomes of mouse peritoneal MCs and mouse bone marrow derived MCs (BMMCs) revealed both similarities and major differences. Strikingly, cathepsin G was the most highly expressed granule protease in human skin MCs, in contrast to the almost total absent of this protease in both mouse MCs. Transcript levels for the majority of cell surface receptors were also very low compared to the granule proteases in both mouse and human MCs, with a difference of almost two orders of magnitude. An almost total absence of T cell granzymes was observed in human skin MCs, indicating that granzymes have no or only a minor role in human MC biology. Ex vivo skin MCs expressed high levels of selective immediate early genes and transcripts of heat-shock proteins. In validation experiments, we determined that this expression was an inherent property of the cells and not the result of the isolation process. Three to four weeks in culture results in an induction of cell growth related genes accompanying their expansion by 6-10-fold, which increases the number of cells for in vitro experiments. Collectively, we show that cultured human skin MCs resemble their ex vivo equivalents in many respects and are a more relevant in vitro model compared to mouse BMMCs for studies of MC biology, in particular human MC biology.

In contrast to Th1 immune responses against pathogenic viruses and bacteria, the incipient events that generate Th2 responses remain less understood. Part of the difficulty in identifying universal operating principles stems from the diversity of entities against which cellular and molecular Th2 responses are produced. Indeed, such responses are launched towards harmful macroscopic parasites and noxious substances such as venoms but also against largely innocuous allergens. This suggests that the canonical understanding about sensing and recognition applied to Th1 responses may not be translatable to Th2 responses. This review will discuss processes and signals known to occur in Th2 responses, particularly in the context of food allergy. We propose that perturbations of homeostasis at barrier sites induced by external or internal subverters that either activate the immune system or lower its threshold activation are the major requirement for allergic sensitization. Innate signals produced in the tissue under these conditions equip dendritic cells with a program that shapes an adaptive Th2 response.

The hyperspectral vegetation index was defined based on the distinctive features of the spectral curve. In alignment with the growth and development characteristics of cotton, the spectral reflectivity of the cotton canopy was computed at different growth stages. The aim of this study was to clarify the association between cotton yield and canopy spectral indices and to develop yield estimation models utilizing hyperspectral imaging. The ASD Field Spec Pro VNIR 2500 spectrometer radiometer was employed to collect spectral reflectance data from cotton canopies at various growth stages. Using spectral analysis techniques, quantitative models were developed based on hyper-spectral vegetation indices, including Normalized Difference Vegetation Index (NDVI) (NDVI) and Radar Vegetation Index (RVI) to extract characteristic information from the cotton canopies. Following thorough testing and precise monitoring of the estimation models, the most optimal models representing cotton canopy structure parameters were identified. Results demonstrate that the power function model, relying on NDVI, provides the most accurate forecasting for Leaf Area Index (LAI)). Additionally, the exponential function model based on RVI proves to be the most effective for predicting cotton unit area above-ground fresh biomass, while another exponential function model based on RVI is identified as the best for predicting cotton unit area above-ground fresh biomass. Clearly, the application of hyper-spectral remote sensing technology enables the analysis, simulation, assessment, and providing scientific basis for precision cotton planting and cotton field management strategies.

In this paper, a relatively new hyper convolution spectra for characterization liquid, viscoelastic and solid samples is presented. Special attention is paid to the biophysical characterization of epithelial tissues and early detection of cancer of the skin, cervix, colon, and oral cavity. The method is based on the use of two types of white light, diffuse and polarized, from the same LED light sources. Based on the subtraction of the intensity values of these two lights and using the hyper convolution algorithm, the ratio of paired and unpaired electrons of tissue is obtained. This ratio correlates well with the state of the tissue: normal, irritating, precancerous, and cancerous. First, a proof-of-concept studies were performed, and later clinical studies on samples from one thousand two hundred fifteen people were performed. It showed that hyper Opto-Magnetic Imaging Spectroscopy (OMIS) can detect epithelial tissue cancers with an accuracy of 85-96%. Bearing in mind that the OMIS method also acquires the biophysical characteristics of the deeper skin layers (epidermis, basement membrane, dermis) by analysing convolution spectra of RGB channels of both diffuse and polarized white light, it is possible to apply this method in cosmetics (skin hydration, collagen, and elastin states, etc.). During OMIS applications, we noticed places where improvements could be made to increase method’s accuracy using advanced machine learning methodologies.

Hyper duplex stainless steels, HDSS, are a new alloy group of duplex stainless steels with the highest corrosion resistance and mechanical properties among the existing modern stainless steel. Due to the addition of extra high content of alloying elements, e.g. Cr, Ni, Mo, etc., the crystallization behavior of the δ-ferrite from the liquid is of vital importance for controlling the steel properties. In this work, the effect of cooling rate (i.e. 4°C/min and 150 °C/min) on the growth process of δ-ferrite in S33207 during the solidification process was investigated using high-temperature confocal scanning laser microscopy (HT-CLSM) in combination with electron microscopes and thermodynamic calculation. The results showed that the solidification mode of S33207 steel was a ferrite-austenite type (FA mode). L→δ transformation occurred at a certain degree of supercooling, and merging occurred during the growth of δ phase dendrites. Similar microstructures were observed after solidification under these two different cooling rates. The variation of area fraction of δ ferrite at the free surface and temperature as well as time during solidification of S33207 steels were calculated at different cooling rates of 4 °C/min and 150 °C/min, respectively. The current HT-CLSM study provides in-situ experimental evidence to confirm that a low cooling rate favored the growth of primary δ-ferrite, whereas a high cooling rate favored the nucleation of primary δ-ferrite during the solidification process. The post-microstructure as well as composition evolution is also briefly investigated. This work shed light on the real time insights for the crystallization behavior of hyper duplex stainless steels during solidification, which aims to contribute to the process control of manufacturing of this steel grade.

Low pressure fluid transport (1) applications often require low and precise volumetric flow rates (2) including low leakage to reduce additional costly and complex sensors. A peristaltic pump de-sign (3) was realized, with the fluid’s flexible transport channel formed by a solid cavity and the wobbling plate comprising a rigid and a soft layer (4). In operation, the wobbling plate is driven externally by an electric motor, hence, the soft layer is contracted and unloaded (5) during pump-cycles transporting fluid from low to high pressure sides. A thorough characterization of the pump system is required to design and dimension the components of the peristaltic pump. To capture all these parameters and their dependencies on various operation-states, often complex and long-lasting dynamic 3D FE-simulations are required. We present, here, a holistic design methodology (6) including analytical as well as numerical calculations, and experimental valida-tions for a peristaltic pump with certain specifications of flow-rate range, maximum pressures, and temperatures. An experimental material selection process is established and material data of candidate materials (7) (liquid silicone rubber, acrylonitrile rubber, thermoplastic-elastomer) are directly applied to predict the required drive torque. For the prediction, a semi-physical, analyti-cal model was derived and validated by characterizing the pump prototype.

The prevalence of allergic diseases, including food allergy, is increasing, especially in developed countries. Implementation of an elimination diet is not a sufficient therapeutic strategy in patients with food allergy, whose quality of life is significantly impaired. In recent years, new effective therapeutic strategies have been developed, such as the application of oral, sublingual, and epicutenous immunotherapy. Oral immunotherapy is the most often applied strategy because of its effectiveness and ease of application, with an acceptable safety profile. The effectiveness of oral immunotherapy in patients with egg, cow's milk and peanut allergy has been proven both in terms of raising of the threshold and the development of tolerance, and in some patients, the development of sustainable unresponsiveness. Although oral immunotherapy is an effective treatment for food allergy, several limitations, including long duration and a significant rate of reported adverse events, reduces its success. Therefore, new therapeutic options, such as treatment with biologicals, either as combinations with food allergen immunotherapy or as monotherapy with the aim of improving the efficacy and safety of treatment are being investigated..

The post-hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid-immunotherapy (AIT). Previously, we have shown that one subpopulation of T regulatory cells results in phenotypically identifiable as functionally potentiated and memory cells in allergic children after 12 months of this immunoactive treatment. Indeed, AIT is the only known treatment able to reshape the detrimental immune response against the allergen into a not noxious one. Besides, VD is widely considered an immunoregulatory molecule endogenously produced and exogenously provided with foods and supplements that might interact with AIT mechanism and affect its outcome. Therefore, a post-hoc analysis of the clinical and immunological data of three different cohorts of allergic patients was performed. One cohort (N=70) was on standard symptoms-controlling pharmacological treatment while the other two (N=60 and N=35, respectively) were treated with AIT for 12 months. Among the first were observed a lower mean endogenous VD level (&lt;22 ng/ml) along with worse symptoms and higher use of medications. Remarkably, the comparison between two sub-cohorts of patients with serum VD above (N=32) or below (N=28) a cut-off value set at mean value (27 ng/ml) revealed that optimal improvement of all clinical and immune parameters was achieved (as expected by effective AIT), irrespective of the VD level. Notably, the third analysis, carried out on one cohort of AIT patients also taking concomitantly VD3 as food supplement (N=19), was distinguished by uppermost overall treatment outcome (amelioration of symptoms, lowest medications requirement, and reduction of total and allergen-specific IgE) as well as the increase of allergen-specific tolerogenic memory T regulatory cells. These findings suggest that endogenous VD level affects allergy severity and allergen immunotherapy effectiveness. Also, VD3 might be investigated as an add-on supplement to get the best out of immunotherapy in VD deficient/insufficient allergic patients. The immunogenic but low-allergenic mite allergoid used as bioactive agent might have contributed to minimize allergic and highlight immunological effects described here.

Deficient wound healing is frequently observed in patients diagnosed with diabetes, a clinical complication that compromises mobility and leads to limb amputation, decreasing patient autonomy and family lifestyle. Fibroblasts are crucial for secreting the extracellular matrix to pave the wound site for endothelial and keratinocyte regeneration. The biosynthetic pathways for collagen production are one of the main components of the extracellular matrix, as the crosslinking of extracellular collagen fibers is intimately related to fibroblast redox homeostasis. In this study, human dermic fibroblasts were cultured with 1 mM sodium selenite (inorganic) and 1 mM of two selenium amino acids (organic), Se-cysteine and Se-methionine. This concentration was compatible with long-term exposure necessary for extracellular matrix production and allowed us to examine the impact of these three compounds on the state and response of the thiol-based HyPer biosensor expressed in the cytoplasm. In addition, the abundance of extracellular matrix and ultrastructural properties were evaluated by Picrus Sirius red staining and scanning electronic microscopy, respectively. We also evaluated whether these selenium compounds effectively ameliorated the perturbations induced by culturing fibroblasts at high glucose levels (25 mM) regarding cytoplasmic redox, extracellular matrix, and glycation on collagen fibers. Our results indicate that cytoplasm protein oxidation was sensitive to selenium compound supplementation. Selenium amino acids increased the sensitivity to protein oxidation, and only Se-cysteine increased the disulfide bond reduction in fibroblasts maintained in high glucose. Despite the lack of effect of selenium compounds on the glu-cose-induced increase in matrix fiber thickness, we found that endothelial migration improved in the matrix generated by high glucose-cultured fibroblasts.

The soil and groundwater of Bhagobangola I block of Murshidabad district, West Bengal, India is severely arsenic contaminated. A bacterium was isolated from the garden soil of Mahishasthali village, which could tolerate 36.49 mM arsenic (III), 280.44 mM arsenic (V) and 63 mM chromium (III), which makes it arsenic (III & V) and chromium (III) hyper-tolerant bacterium. The growth pattern of this bacterium does not show much alteration in presence of 10 mM arsenic (III) and chromium (III), emphasizing its resistance to these heavy metals. Scanning electron microscopy depicted the size of this bacterium to be ~1.45 µm. 16S rDNA sequencing followed by subsequent phylogenetic analysis established the identity of this bacterium as Microbacterium paraoxydans. The bacterium is capable of bioremediation of arsenic and showed 30.8% & 22.6%, and 35.2% and 30.5% of bioremediation over a period of 24 and 48 hours in 1 mM and 4 mM arsenite, respectively. Microbacterium paraoxydans also exhibit plant growth promoting properties like nitrogen fixation, phosphate solubilization, indole-3-acetic acid production and production of siderophores. Therefore, the heavy metal resistance, bioremediation potential and plant growth promoting potential of the bacterium could be utilized not only for reduction of arsenic toxicity in soil and groundwater but also for plant growth promotion by using it as a biofertilizer.

Genetic Programming (GP) is a powerful Machine Learning (ML) algorithm that can produce readable white-box models. Although successfully used for solving an array of problems in different scientific areas, GP is still not well known in Remote Sensing. The M3GP algorithm, a variant of the standard GP algorithm, performs Feature Construction by evolving hyper-features from the original ones. In this work, we use the M3GP algorithm on several sets of satellite images over different countries to create hyper-feature from satellite bands to improve the classification of land cover types. We add the evolved hyper-features to the reference datasets and observe a significant improvement of the performance of three state-of-the-art ML algorithms (Decision Trees, Random Forests and XGBoost) on multiclass classifications and no significant effect on the binary classifications. We show that adding the M3GP hyper-features to the reference datasets brings better results than adding the well-known spectral indices NDVI, NDWI and NBR. We also compare the performance of the M3GP hyper-features in the binary classification problems with those created by other Feature Construction methods like FFX and EFS.

Hyper spectral imaging (HSI) is a technique that is used to obtain the spectrum for each pixel in the image. It helps in finding objects and identifying materials etc. Such an identification is very difficult using other imaging techniques. It allows the researchers to investigate the documents without any physical contact. Nowadays detection of unequal Ink mismatch based on HSI has shown vast improvement in distinguishing the inks. Detection of unequal Ink mismatch is an unbalanced clustering problem. This paper used K-means Clustering for ink mismatch detection. K-means Clustering find same subgroups in the data based on Euclidean distance. This paper demonstrates performance in unequal Ink mismatch based on HSI.

This paper introduces new improvements to the modified version of the BIRECT (BI secting RECTangles) algorithm referred to as BIRECTv. We explore various approaches, by first including a grouping strategy for hyper-rectangles having almost the same sizes by categorizing them into different classes. Therefore constraining them not to exceed a certain pre-defined threshold (a small positive value to define the tolerance level). This approach allows for more efficient computation and can be particularly useful when dealing with a large number of hyper-rectangles with varying sizes. To avoid over-sampling, and preventing redundant or excessive sampling, at some shared vertices in descendant subregions, a particular vertex database is used to limit the number of samples taken within each subregion to two. The experimental investigation shows that these improvements have a positive impact on the performance of the BIRECTv(imp.) algorithm and the proposal is a promising global optimization algorithm compared to the original BIRECTv algorithm and its variants. Additionally, the BIRECTv(imp.) algorithm showed particular efficacy in solving high-dimensional problems.

U-Net, based on a deep convolutional neural network (CNN), has been clinically used to au-to-segment normal organs and potentially target volumes. However, CNNs with local geometric dependencies may limit the accuracy of segmentation. Additionally, the performance of CNNs can vary depending on the selection of network hyper-parameters, which was mitigated by the proposition of nnU-Net. We chose a vision transformer architecture called VT U-Net, which features a self-attention excluding the convolution layer, to overcome the limitations of CNNs by utilizing global geometric information of images. The VT U-Net v.2 became more powerful thanks to the adaptive hyper-parameter optimizer embedded in nnU-Net. However, despite leveraging the benefits of nnU-Net, VT U-Net v.2 still had additional network hyper-parameters that needed to be optimally chosen. Accordingly, among various hyper-parameters, this study attempted to find the optimal combination of the patch size and the embedded dimension regarding the transformer. From the 4-fold cross-validation, the modified VT U-Net v.2 showed the highest average performance for planning target volume (PTV) segmentation among the investigated networks. Though nnU-Net was based on convolution layers, the adaptive hyper-parameter optimizers turned out to enhance the performance. It was also confirmed that network hyper-parameters affected the segmentation accuracy of vision transformers.

Vascular endothelial growth factors (VEGFs) are regarded as the key vasculogenic mediators in the human body, of which VEGF-A is considered as one of the important types. It is the major growth factor possessing increasing vascular permeability as well as angiogenesis properties. This article provides intuition into the different effects of VEGF-A on vessels in ovarian hyper stimulation syndrome (OHSS) which is defined as a complication of in-vitro fertilization for infertility treatment, and obesity, a universally health problem. These are two dissimilar pathways outcomes for VEGF-A effects, thereby This article reviews updated information about the mentioned disorders and reveals that how this kind of growth factor yields different results on vasculature by activating distinct intracellular signaling in endothelial cells.

This paper reports a new global Mittag-Leffler synchronization criterion with regard to fractional-order hyper-chaotic financial systems by designing the suitable impulsive control and the state feedback controller. The significance of this impulsive synchronization lies in the fact that the backward economic system can synchronize asymptotically with the advanced economic system under the effective impulse macroeconomic management means. Matlab LMI-toolbox is utilized to deduce the feasible solution in numerical example, which shows the effectiveness of the proposed methods. It is worth mentioning that the LMI-based criterion usually requires the activation function of the system to be Lipschitz, but the activation function in this paper is fixed and truly nonlinear, which cannot be assumed to be Lipschitz continuous. This is another mathematical difficulty overcome in this paper.

Full waveform (FW) LiDAR holds great potential for retrieving vegetation structure parameters at a high level of detail, but this prospect is constrained by practical factors such as lack of available handy processing tools and technical intricacy of waveform processing. This study introduces a new product, named the Hyper Point Cloud (HPC) derived from FW LiDAR data, and explore its potential applications such as tree crown delineation using the HPC-based intensity and percentile height (PH) surfaces, which show a promising solution to the constraints of using FW LiDAR data. Results of the HPC present a new direction to handle FW LiDAR data and offer prospects for studying the mid-story and understory of vegetation with high point density (~ 182 points/m2). The intensity-derived digital surface model (DSM) generated from the HPC shows that the ground region has larger maximum intensity (MAXI) and mean intensity (MI) than the vegetation region while having smaller total intensity (TI) and number of intensities (NI) at the given grid cell. Our analysis of intensity distribution contours at individual tree level exhibit similar patterns, indicating that the MAXI and MI are decreasing from the tree crown center to tree boundary while a rising trend is observed for TI and NI. These intensity variable contours provide a theoretical justification for using HPC-based intensity surfaces to segment tree crowns and exploit their potential for extracting tree attributes. The HPC-based intensity surfaces and the HPC-based PH Canopy Height Models (CHM) demonstrate promising tree segmentation results comparable to the LiDAR derived CHM for estimating tree attributes such as tree locations, crown widths and tree heights. We envision that products such as the HPC and the HPC-based intensity and height surfaces introduced in this study can open new perspectives to use FW LiDAR data and alleviate the technical barrier of exploring FW LiDAR data for detailed vegetation structure characterization.

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pre-treated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1), by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.

A series of derivatives, involving two dithienylethene (DTE), groups, connected by several molecular linkers (bis(ethylene-1,2-dithiolato)Ni- (NiBDT), naphthalene, quasilinear oligothiophene chains) are investigated with the aid of computational quantum chemistry methods. This involves the computation of the second- and third-order nonlinear optical properties, i.e. molecular hyperpolarizabilities of the designed/selected derivatives. These properties can be efficiently controlled by DTE switches, in connection with light of appropriate frequency. We found that NiBDT, as a linker, is associated with a greater contrast, in comparison to naphthalene, between the first and second hyperpolarizabilities of the “open-open” and the “closed-closed” isomers. This is explained by invoking the low lying excited states of NiBDT. It has been found that the second hyperpolarizability can be used as an index, which follows the structural changes induced by photochromism. The two-photon absorption, which is related to the imaginary part of second hyperpolarizability, has also been investigated for the S0S1 transition. Furthermore, the intramolecular excited-state energy transfer (EET) is studied as well as the overlap between the absorption and emission spectra of the donor and acceptor groups of the molecules. The electronic coupling, VDA, between the donor and acceptor fragments, as well as the emission spectrum of the donor and the absorption spectrum of the acceptor have been computed, assuming a Förster type transfer mechanism. EET is a critical factor governing the photochromism. Two methods were used to compute VDA, one based on linear response and one based on the distributed multipole analysis (DMA); both techniques give very similar results for the dominating Coulomb contribution. For NiBDT as the linker a low VDA value has been computed. We found that VDA is affected by the molecular geometry. Our results clearly show that the linker strongly influences the communication between the open-closed DTE groups and thus, photochromism. The present computations show that full photochromism is attained in derivatives where two DTE groups are linked by a tetrathiophene chain, in agreement with experiment. The sensitivity of molecular linear and nonlinear optical properties upon photochromism can assist with the identification of the molecular isomers.

Electricity demand forecasting plays a significant role in energy markets. Accurate prediction of electricity demand is the key factor to optimize power generation, consumption, saving energy resources, and determining the energy prices. However, integrating energy mix scenarios, including solar and wind power which are highly non-linear and seasonal, into an existing grid increases uncertainty in generation, adds the challenges for precise forecast. To tackle these challenges, state-of-the-art methods and algorithms have been implemented in literature. We have developed Artificial Intelligence (AI) based deep learning models that can effectively handle the information of long time-series data. Based on the pattern of dataset, four different scenarios were developed and two best scenarios were selected for prediction. Dozens of models were developed and tested in deep AI networks. In the first scenario (Scenario1), data for weekdays excluding holidays was taken and in the second scenario (Scenario2) all the data in the basket was taken. Remaining two scenarios, weekends and holidays were tested and neglected because of their high prediction error. To find the optimal configuration, models were trained and tested within a large space of alternatives called hyper-parameters. In this study, an Aritificial Neural Network (ANN) based Feed-forward Neural Network (FNN) showed the minimum prediction error for Scenario1 while a Recurrent Neural Network (RNN) based Gated Recurrent Network (GRU) showed the minimum prediction error for Scenario2. While comparing the accuracy, the lowest MAPE of 2.47% was obtained from FNN for Scenario1. When evaluating the same testing dataset (non-holidays) of Scenario2, the RNN-GRU model achieved the lowest MAPE of 2.71%. Therefore, we can conclude that grouping of weekdays as Senario1 prepared by excluding the holidays provides better forecasting accuracy compared to the single group approach used in Scenario2, where all the dataset is considered together. However, Scenario2 is equally important to predict the demand for weekends and holidays.

Keywords: Adrenergic signaling in cardiomyocytes; cardiac muscle contraction; Chagas disease; diabetic cardiomyopathy; dilated cardiomyopathy; glycerolipid metabolism; glycolisis/glucogenesis; hypertrophic cardiomyopathy; purine metabolism; steroid hormone biosynthesis.