Agroindustrial by-products constitute an alternative source of feed livestock, and their use contributes to the sustainability of livestock systems and the circular bioeconomy. The effects of replacing cereal (0%, 40% and 80%) with dehydrated orange pulp (DOP) in the diet of goats on the antioxidant and fatty acid (FA) contents of cheeses were evaluated. For a more suitable understanding of the role of coagulant enzymes in establishing the properties of the cheese, the effect of milk-clotting with animal and vegetable rennet was also analysed. The rennet did not substantially affect the FA or the antioxidant compounds, and the use of DOP did not affect the FA contents. However, the α-tocopherol levels, total phenolic compounds (TPC), and total antioxidant capacity (TAC) in cheeses increased as the percentage of DOP replacing cereals increased. Moreover, the high correlation obtained between the TAC and the TPC (r = 0.73) and α-tocopherol (r = 0.62) contents indicated the important role played by these compounds in improving the antioxidant capacity of the cheese. In conclusion, DOP is a suitable alternative to cereals in the diet of goats and improves the antioxidant status of the cheese produced.

In recent times, using image-based deep learning techniques has been very useful for classifying fruits. However, mango is a particular challenge because its shelf life is directly related to the degree of maturity at the time of harvest, which is determined mainly through the visual assessment of the operators when sorting them, doing it incorrectly, coupled with the blows and compressions exposed during storage and transport, trigger the deterioration in their quality, hence the importance of this operation. In this sense, the purpose of this study focuses on designing a computational model based on Deep Learning that uses a convolutional neural network (CNN) parameterized to select mangoes according to their color tone based on their maturity stage. A dataset was established from 201 labeled images, then a CNN architecture was built, obtaining a model on which 3 criteria were evaluated: the number of convolution and grouping layers, the resolution of the input images and the number of training epochs required. As a result, an input image resolution of 32 x 32 pixels was achieved, the process included a convolution layer followed by pooling that fed another layer that processed the results and ended in an output layer with 2 neurons under the One Hot Encoding representation. The model required 20 epochs to perfect its training, achieving 96.04 % accuracy in mango image selection. This study supports the potential of CNNs in quality analysis through mango color selection, even in uncertainty scenarios.

The liver health of Gilthead sea bream and European sea bass fed fishmeal-free diets including various proportions of plant proteins, insect and poultry by-product meals, was investigated through biochemical and histological analyses using a new Liver Index (LI) formula. Four isoproteic (45% DM) and isolipidic (20% DM) diets were compared: a control, plant-based diet (CV) and other three test ones where 40% of a plant protein-rich ingredient mixture was replaced by Hermetia illucens (H40) or poultry by-product (P40) meals alone or in combination (H10P30). The trials lasted 12 and 18 weeks for sea bream and sea bass, respectively. The results so far ob-tained highlighted species-specific differences in the physiological response to dietary changes. In sea bream, the biochemical and histological responses suggest favorable physiological status and liver health, with higher serum cholesterol (CHO) and triglyceride (TAG) levels and moderate hepatocyte lipid accumulation with the H10P30 diet compared to CV (p<0.05). In sea bass, all diets resulted in elevated serum TAG levels and liver lipid accumulation particularly in fish fed the P40 one (p<0.05) which resulted in the highest LI, coupled with higher frequency of severe lipid accumulation, hypertrophy, cord loss, peripheral nuclei displacement and pyknosis. In conclusion sea bream well adapted to the test diets, while sea bass exhibited altered hepatic lipid metabolism leading to incipient liver steatosis, likely due to the high lipid content of the diets including the insect and poultry meals. The LI developed in this study proved to be a reliable tool for assessing the effects of dietary changes on liver health of sea bream and sea bass, consistent with biochemical and histological findings.

Most authors have investigated the role of mannoproteins on wine quality but very few analyze the use of grape derived polysaccharides as they are not commercially available. Purified grape derived polysaccharides from red wine (WPP) and winemaking by-products (DWRP: Distilled Washing Residues Polysaccharides) were used as potential fining agents to modulate white wine flavour. Phenolics and volatile compounds were analyzed in control and wines treated with WPP, DWRP and commercial mannoproteins (CM) after one and twelve months of bottling, and a sensory analysis was conducted. WPP and DWRP, rich in rhamnogalacturonans-II, showed as good modulators of wine aroma and astringency. Improvement of wine aroma was related to an increase of all volatile families expect higher alcohols and volatile acids. The modulation of astringency and bitterness was related to a reduction in the proanthocyanidin content and its mean degree of polymerization. Extracts with polysaccharides with higher protein contents presented higher retention of volatile compounds, and DWRP extract showed more positive effects on the overall aroma. Our novel results open the possibility of obtaining valuable polysaccharides from distilled washing residues of wine-pomaces, which could promote its valorization as by-product. This is the first time to describe the potential use of this by-product.

Longitudinal image registration of pulmonary computed tomography (PCT) images may serve as an essential tool for investigating the relationship between radiation dose distribution and the occurrence and phenotype of radiation-induced lung disease (RILD). Although numerous longitudinal registration algorithms have been developed for PCT, most similarity-based approaches are not suitable for PCT involving RILD due to the complex tissue variation between two PCT images. Moreover, conventional feature-based approaches might fail to find a sufficient number of matched pairs of feature points due to the disparate lung deformation caused by breathing and RILD. To overcome the challenges resulting from RILD, component structure coherence point drift (CSCPD) was proposed to establish a deformation model by decomposing the chest into several components and matching them with individual parameters based on coherence point drift (CPD). Moreover, a regional vascular point matching (RVPM) algorithm was proposed to generate a vascular subtree and to substantially increase the number of corresponding pairs between two images. Eventually, the components were recomposed and aligned by a thin plate spline algorithm. A performance assessment on 15 pairs of PCT images of patients with RILD yielded recall and precision values of 0.85 and 0.89 for RVPM, respectively. Moreover, the target registration error of CSCPD with RVPM (2.3 ± 1.79) was significantly better than that of conventional CPD with RVPM (2.95 ± 1.89) and conventional CPD (5.04 ± 2.87). Therefore, the proposed registration system is robust enough to address the disparate deformation of lungs with RILD, and it improves registration accuracy within the parenchyma.

In bioprocess engineering the Qualtiy by Design (QbD) initiative encourages the use of models to define design spaces. However, clear guides on how models for QbD are validated are still missing. In this review we provide a comprehensive overview about validation methods, mathematical approaches and metrics currently applied in bioprocess modeling. The methods cover analytics for data used for modeling, model training and selection, measures for predictiveness and model uncertainties. We point out general issues in model validation and calibration for different types of models and put this into context of existing health authority recommendations. This review provides the start-point for developing a guidance for model validation approaches. There is no one-fits-all approach but this review shall help to identify the best fitting validation method or combination of methods for the specific task and type of bioprocess models that is developed.

Aptamers are versatile oligonucleotide ligands used for molecular recognition of diverse targets. However, application of aptamers to the field of amyloid β-protein (Aβ) has been limited so far. Aβ is an intrinsically disordered protein that exists in a dynamic conformational equilibrium, presenting time-dependent ensembles of short-lived, metastable structures and assemblies that have been generally difficult to isolate and characterize. Moreover, despite understanding of potential physiological roles of Aβ, this peptide has been linked to the pathogenesis of Alzheimer disease, and its pathogenic roles remain controversial. Accumulated scientific evidence thus far highlights undesirable or nonspecific interactions between selected aptamers and different Aβ assemblies likely due to metastable nature of Aβ or inherent affinity of RNA oligonucleotides to β-sheet-rich fibrillar structures of amyloidogenic proteins. Accordingly, lessons drawn from Aβ–aptamer studies emphasize that purity and uniformity of the protein target and rigorous characterization of aptamers’ specificity are important for realizing and garnering the full potential of aptamers selected for recongizing Aβ or other intrinsically disordered proteins. This review summarizes studies of aptamers selected for recognizing different Aβ assemblies and highlights controversies, difficulties, and limitations of such studies.

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, USFDA has given expedited approval to bedaquiline (BDQ), as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis but due to poor solubility desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of Bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of Bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88±2.1 nm with a zeta potential of 21.16 mV. In vitro, studies showed enhanced drug release with a high degree of stability at 25 ± 2 ºC & 60 ± 5 % and 40 ± 2 ºC & 75± 5 %. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

Precise monitoring of different environmental parameters and contaminations during food processing and storage is a key factor for maintaining its safety and nutritional value. Thus, developing reliable, efficient, cost-effective sensor devices for these purposes is of utmost importance. In this paper, we show that Poly-(diallyl-dimethylammonium chloride)/reduced Graphene oxide (PDAC/rGO) films produced by a simple Layer-by-Layer deposition can be effectively used to monitor temperature, relative humidity and the presence of volatile organic compounds as indicators for spoilage odors. At the same time, they show potential for electrochemical detection of organophosphate pesticide dimethoate. By monitoring the resistance/impedance changes during temperature and relative humidity variations or upon the exposure of PDAC/rGO films to methanol, good linear responses were obtained in the temperature range of 10-100 °C, 15-95 % relative humidity, and 35 ppm - 55 ppm of methanol. Moreover, linearity in the electrochemical detection of dimethoate is shown for the concentrations in the order of 102 µmol dm−3. The analytical response to different external stimuli and analytes depends on the number of layers deposited, affecting sensors’ sensitivity, response and recovery time, and long-term stability. The presented results could serve as a starting point for developing advanced multimodal sensor devices and sensor arrays with high potential for analytical applications in food safety and quality monitoring.

The goods and services produced by forest and vegetation ecology system is the power by which human society can be promoted fast in high-quality and sustainable way. With the increase of population and economic development in water-limited regions, there is an increasing demand for the quantity and variety of forest vegetation ecosystem products and services. To meet the demands of this situation, most of the original forest has changed into farmland, non-native forest and grass land. As a result, water-plant relationship changed from equilibrium to non-equilibrium, which led to soil drought, soil degradation and vegetation decline in dry years or waste of soil water in rainy years in most of water-limited regions. In order to solve the questions and realize the sustainable utilization of soil water resources and the high quality and sustainable development of social economy, it is necessary to apply the utilization limit theory of soil water resources by plants and the theory of soil water carrying capacity for vegetation to adjust the relationship between plant growth and soil moisture to obtain the maximum yield and benefit of vegetation and serve high-quality and sustainable development.

Nowadays, the high demand for healthy foods and sustainable products, has led the food industry to explore innovative food technologies, such as fortification with bioactive compounds like antioxidants and polyphenols, that may be sourced from herbs or by-products. The aim of the present study was to explore the enrichment of refined olive oils with natural bioactive compounds such as the herbs rosemary (salvia rosmarinus), basil (ocimum basil), sage (salvia officinalis), lemon balm (melissa oficinallis), st. john’s wort (hypericum perforatum), pink savory (Thymbra satureja), dittany (origanum dictamnus), and by-products such as pomace from olives, olive leaves (olea europaea tree), orange peel (citrus sinensis), lemon peel (citrus limon), pomegranate peel (punica granatum) and mandarin peel (citrus reticulate). The fortification of the refined olive oils was performed with the use of different methodologies such as Conventional maceration (CM), Incubation shaking maceration (ISM), and Ultrasound assisted maceration (UAM). Their phenolic content and antioxidant capacity were measured with Folin–Ciocalteu assay and Ferric Reducing Antioxidant Power (FRAP) assay respectively. All methods demonstrated that different parameters such as time of maceration, temperature and sample concentration, play an important role in the fortification process of the refined olive oils. The predicyed bioavailability of the antioxidant and phenolic compounds in the fortified oils was determined with in vitro digestion and ranged from 4.84% to 53.11%. Furthermore, the refined olive oils fortified with pomace, basil, st. john's wort, and pomegranate peel presented the highest antioxidant and phenolic predicted bioavailability indices during the in vitro process compared to the control refined olive oil. Finally, fortification with natural herbs or by-products can be considered an innovative method for the improvement of the nutritional value of refined olive oils.

This paper explores ballot split by type and introduces universal measures of democratic power flow and accountable local representation. These measures allow definitive comparison of electoral systems between countries, and choice of a new electoral system within a country based on existing data and with minimum assumptions.

Adaptive radiations occur mostly in response to environmental variation through the evolution of key eco-morphological innovations that allow emerging species to occupy new ecological niches. However, rapid phenotypic evolution and the evolution of key novelties are likely to also occur when a couple or few species are engaged into narrow ecological interactions. To demonstrate coevolution is a difficult task; only elusive evidences confirm that coevolution is a driver of speciation and diversification. Here we propose that the adaptive radiation of the Mediterranean orchid genus Ophrys, which gave rise to ca. 350 species since the apparition of the genus is due to the particular co-evolutionary dynamics between these plants and their pollinators. We suggest that the pollination by sexual swindle used by Ophrys orchids is the main driver of this coevolution. Flowers of each Ophrys species mimic sexually receptive females of one particular insect species, mainly bees. Male bees are attracted by pseudo-pheromones emitted by Ophrys flowers that are similar to the sexual pheromones of their females. Males lured by the flower shape, color and hairiness attempt to copulate with the flower, which glues pollen on their bodies. Pollen is eventually transferred to the stigma of another flower of the same Ophrys species during similar copulation attempts. Three observations led us to propose the scenario of an asymmetric co-evolutionary relationship between Ophrys and their pollinators. Firstly, there is a strong intra-specific competition among Ophrys individuals for the attraction of their species-specific pollinators, which is due to the high learning and memorization abilities of bees that record the pheromone signatures of kin or of previously courted partner to avoid (further) copulation attempts. Mnemonic pollinators induce thus a strong selective pressure for variation in the pseudo-pheromones emitted by individual flowers, which will potentially generate shifts in pollinator species, and hence Ophrys speciation. These pollinator shifts are adaptive for new Ophrys species because they may benefit from a competitor-free space. Secondly, such shifts in pollinator species are due to the random crossing of peaks in the olfactory landscape of the pollinator guild that is syntopic to each particular Ophrys population. This selective process on individual, random variation in pseudo-pheromone bouquets is followed by directional selection on flower phenotypes that will reinforce the attraction of the new pollinator. Thirdly, pollinators use the pseudo-pheromones emitted by Ophrys to locate suitable habitats from a distance within complex landscapes. Pollinators stay fixed for a while in these habitats by the local diversity of pseudo-pheromones, which increases their probability of encounter with a receptive female and hence the reproduction probability of both sexes. Conversely, pollinators disperse out of small suitable habitats once they have memorized the local diversity of sexual pseudo-pheromone bouquet or if fecundated Ophrys flowers repel pollinators, which decreases the probability of geitonogamy (plant advantage) but limit pollinator mating with locally emergent insect females, thus limiting inbreeding and favoring gene flow (pollinator advantage). Finally, we propose several research avenues that emerged according to this scenario of adaptive radiation by assymetric coevolution between Ophrys species and their pollinators.

A model of space-time is presented, whose origin is set before the appearance of any universe. It uses concepts of previous work, a central one being that the information about the laws of nature is stored locally everywhere in space such that all physical processes obey them. Since information storage is bound to matter or energy, space is assumed to consist of dark energy (DE), which thus assumes an importance far beyond its function as a stopgap for an energy deficit in our universe ( U ). The primordial state (PS) is a timeless and relatively large space of 3 dimensions described by a Wheeler DeWitt (WDW) equation, whose solution is interpreted as an arrangement of very many space quanta and possesses properties that remind of the time-honored concept of the unmoved mover. The comparison of WDW solutions belonging to different mass densities of the DE favors one in which the space quanta are mini black holes. This allows the space quanta to be imagined as mass points which are kept at a distance compatible with the quantum volume by the Pauli principle or something equivalent. Triggered by a dramatic increase in probability, the PS is followed by a time-controlled sequence of quantized expansion states (ES i ). The concomitant emergence of time occurs in a lightning huge crash, consuming almost all DE of the PS. The subsequent quantized ES i emerge from a WDW equation, novelly derived from a solution of the modified cosmic momentum equation, which classically describes an exponential space expansion (CS). The huge volme of the ES i is also used as size of the PS. Information is assumed to be geometrically stored in arrangements of space quanta similar to how genetic information is stored in DNA molecules. During the CS information must be transferred from already existing "information quanta" to new ones. This requires time, slows down the expansion and is taken into account by a friction term in the cosmological momentum equation thus modified. Since the Friedmann-Lemaître (FL) equation remains fully valid, the model is widely based on recognized equations, so that some results may be understood as interpretations.

Limiting harm to organisms via genetic sampling is an important consideration for rare species. Nondestructive sampling techniques have been developed to address this issue in freshwater mussels. Two methods, visceral swabbing and tissue biopsies, have proven to be effective for DNA sampling, though it is unclear as to which method is preferable for genotyping-by-sequencing (GBS). Tissue biopsies may cause undue stress and damage to organisms, while visceral swabbing potentially reduces the chance of such harm. Our study compared the efficacy of these two DNA sampling methods for generating GBS data for the Unionid freshwater mussel, Texas Pigtoe (Fusconaia askewi). Our results find both methods generate quality sequence data, though some considerations are in order. Tissue biopsies produced significantly higher DNA concentrations and larger numbers of reads when compared to swabs, though there was no significant association between starting DNA concentration and number of reads generated. Swabbing produced greater sequence depth (more reads per sequence) while tissue biopsies revealed greater coverage across the genome (at lower sequence depth). Patterns of genomic variation as characterized in principal component analyses were similar regardless of the sampling method, suggesting that the less invasive swabbing is a viable option for producing quality GBS data in these organisms.

(1) Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding of at least two TFs to genomic DNA is the widespread mechanism of transcription regulation. Massive analysis of co-occurrence of overrepresented pairs of motifs (composite elements, CEs) for different target TFs studied in ChIP-seq experiments can clarify the mechanisms of TF cooperation. (2) Methods: We focused on homotypic CEs representing the same motif models and considered only CEs with spacers. We improved the capability of the Motifs Co-Occurrence Tool (MCOT) to predict asymmetric homotypic CEs in which one of par-ticipating motifs has higher conservation than the other. We categorized the target TFs from the data of M. musculus ChIP-seq and A. thaliana ChIP-seq/DAP-seq according to the structure of DNA-binding domains (DBDs) into classes. (3) Results: For all TF classes the predominance of asymmetric CEs over both symmetric and those with no enrichment in both directions was re-vealed. Target TFs from classes Basic helix-loop-helix factors (bHLH) and Basic leucine zipper factors (bZIP) showed the highest fractions of datasets with asymmetric CEs. We showed that pioneer TFs, despite their DBD types, have a higher significance of asymmetry within homotyp-ic CEs compared to other TFs. (4) Conclusion: Asymmetry within homotypic CEs is a promising new feature decrypting the mechanisms of gene transcription regulation.

The paper presents the main experimental capabilities of the automatic system for the study of the interaction between porous media and atmosphere. This system is one of the possible variants of patent 2-241-477. The paper shows the result of a drying and wetting study of a tailings sample. The sample is 32 cm in height and 29 cm in diameter. The saturation and drying process was carried out at 26 degrees Celsius at the sample surface, an air velocity of 2 m/s and a relative humidity of 60%. The recharge applied to the column surface was 0.3 cm3/cm2/minute. The results show the effectiveness of the system in controlling the spatial-temporal variation of different physical properties of the porous medium in the vertical and surface profile. The controlled variables include volumetric water content, suction, relative humidity, sample weight variation due to recharge or drying, shrinkage, temperature, etc. The experiment shows how the tailings saturate very quickly but dry very slowly. Tailings consolidation occurs in the drying and wetting processes, being higher in the first one.

The diverse socio-economic and environmental impacts that the set-up of a new photovoltaic installation has must be weighed carefully in order to reach the best possible solution. Among the different photovoltaic systems there are several classification criteria, depending on the technology, application and the size of the modules that define them. The size (installed nominal capacity) stands out as an impartial and critical measure in the decision making process. In this article we use a multi-criteria decision making method to analyse the responses of five experts to a detailed questionnaire in which several different criteria are correlated with various photovoltaic installation sizes. The limitation associated to the low number of experts is addressed with a robustness and sensitivity analysis. With this study we seek first, to apply and demonstrate the feasibility of a methodology which combines technical information with multi-criteria decision making methods, and second, to obtain a clear result oriented that increases the benefits of a forthcoming photovoltaic installation of modules in distributed generation adding up to 1GW total peak power in standard conditions. We observe a consistent result in which smaller photovoltaic modules are the ideal solution that maximises the socio-economic benefits of any installation. If a decision has to be taken about the type of photovoltaic plant to be installed, the conclusion is clear: given a certain size, small, easily scalable installations are the best solution for stake-holders, for the inhabitants, and for the environment.

A genome-wide association study (GWAS) was performed on a set of 260 lines which belong to three different bi-parental flax mapping populations. These lines were sequenced to an averaged genome coverage of 19× using the Illumina Hi-Seq platform. Phenotypic data for 11 seed yield and oil quality traits were collected in eight year/location environments. A total of 17,288 single nucleotide polymorphisms were identified, which explained more than 80% of the phenotypic variation for days to maturity (DTM), iodine value (IOD), palmitic (PAL), stearic, linoleic (LIO) and linolenic (LIN) acid contents. Twenty-three unique genomic regions associated with 33 QTL for the studied traits were detected, thereby validating four genomic regions previously identified. The 33 QTL explained 48-73% of the phenotypic variation for oil content, IOD, PAL, LIO and LIN but only 8-14% for plant height, DTM and seed yield. A genome-wide selective sweep scan for selection signatures detected 114 genomic regions that accounted for 7.82% of the flax pseudomolecule and overlapped with the 11 GWAS-detected genomic regions associated with 18 QTL for 11 traits. The results demonstrate the utility of GWAS combined with selection signatures for dissection of the genetic structure of traits and for pinpointing genomic regions for breeding improvement.

The results of physico-chemical studies of individual fruit parts, including crusts, partitions, juice and seeds themselves, extracted from immature (green), unripe and mature fruits of three harvest periods are presented: 20.VII, 01.IX and 15.X. The analyses were carried out in 2019-20 during the period of active growth and ripening of fruits in the varieties Spring, Iridanaly, Guleisha pink and wild pomegranate from the Geokchay region (Azerbaijan) using standard and generally accepted physico-chemical methods. The ripe fruit (130-288 g) consisted of 60-113% of the peel (peel together with partitions), 53-140% of the juice and 17-85% of the seeds themselves. The edible part of the ripened fruits (53.85-73.2 of the total weight of the fruit) consisted of 58.54-78.65% juice and 21.35 -41.46% seeds, fresh juice contained 15.7-17.7% solids, including 12.04-13.84% sugar, 0.17-0.30% protein, 0.15—0.23% pectin, 0.30-0.40% ash and 0.26-0.57% total polyphenols. The concentrations of solids, protein, ash and total polyphenols in the seeds themselves, remaining after the extraction of juice from the grains of ripe fruits, were 50.0-58.2, 4.13-5.75, 0.60-1.0 and 0.08-0.32%, respectively. There were fewer total polyphenols, flavonoids, chlorogenic acids, catechins and leucoanthocyanins in ripe fruits, and more ascorbic acid, anthocyanins and proanthocyanidins than in unripe ones. The period from the second half of July to the beginning of September is the time of a real “boom” of common polyphenols.

BTB domain and CNC homology 1 (BACH1) is a highly expressed transcription factor in tumors including breast and lung, relative to their non-tumor tissues. BACH1 is known to regulate multiple physiological processes including heme homeostasis, oxidative stress response, senescence, cell cycle, and mitosis. In a tumor, BACH1 promotes invasion and metastasis of cancer cells, and the expression of BACH1 presents a poor outcome for cancer patients including breast cancer patients. Recent studies identified novel functional roles of BACH1 in the regulation of metabolic pathways in cancer cells. BACH1 inhibits mitochondrial metabolism through transcriptional suppression of mitochondrial membrane genes. In addition, BACH1 suppresses activity of pyruvate dehydrogenase (PDH), a key enzyme that converts pyruvate to acetyl-CoA for the citric acid (TCA) cycle through transcriptional activation of pyruvate dehydrogenase kinase (PDK). Moreover, BACH1 increases glucose uptake and lactate secretion in aerobic glycolysis through the expression of metabolic enzymes involved such as hexokinase 2 (HK2) and glyceraldehyde 3- phosphate dehydrogenase (GAPDH). Pharmacological or genetic inhibition of BACH1 could reprogramme metabolic pathways, subsequently rendering metabolic vulnerability of cancer cells. Furthermore, inhibition of BACH1 decreased antioxidant-induced glycolysis rates as well as reduced migration and invasion of cancer cells, suggesting BACH1 as a potentially useful cancer therapeutic target.

Aptamers have a well-earned place in therapeutic, diagnostic, and sensor applications, and we now show that they provide an excellent foundation for education, as well. Within the context of the Freshman Research Initiative (FRI) at The University of Texas at Austin, students have used aptamer selection and development technologies in a teaching laboratory to build technical and 21st century skills appropriate for research scientists. One of the unique aspects of this course-based undergraduate research experience is that students develop their own projects, and take ownership of their own science in what would otherwise be a traditional teaching lab setting. Of the many successes, this work includes the isolation and characterization of novel calf intestinal alkaline phosphatase (anti-CIAP) RNA aptamers by an undergraduate researcher. Further, preliminary survey data suggest that students who participate in the aptamer research experience express significant gains in their self-efficacy to conduct research, and their perceived ability to communicate scientific results, as well as organize and interpret data. This work will describe the use of aptamers in an educational setting, highlight the positive student outcomes of the aptamer research experience, and more particularly present the research findings relative to the anti-CIAP aptamer.

Red plum apricot is the best apricot over the world. Since having been introduced into Guyuan county in 1987 from Shaanxi province, red plum apricot grows well and then has been selected as good varieties to popularize in semirid loess hilly regions because the color of red plum apricot is beautiful, aroma fragrant , and taste is the mix of sour and sweet and nutrition is rich. Since 1995, the yield, benefits and planting area of red plum apricot increase doubly, and the distribution range of red plum apricot increased from Guyuan to the whole Ningxia, and then to Gansu province and so on in the water-limited regions, China. However, there are still some problems in the sustainable produce of red plum apricot. In order to promote the development of red plum apricot and meet people's increasing demand, we should do intensive study of the relationship between red plum apricot and environment and the comparison of possible methods to reduce the bad influence of drought, low temperature and frost on quality and production of red plum apricot, and determine the soil water resources use limit by red plum apricot and the suitable leaf amount of red plum apricot when the planting density equal soil water carrying capacity for red plum apricot and select the best method to reduce or evade the bad influence of soil drought, low temperature, frost and soil drought on red plum apricot to ensure the sustainable produce of red plum apricot in Sustainable Produce of red plum apricot in water-limited regions.

The difficult current environmental situation, caused by construction industry residues containing ceramic materials could be improved by using these materials as recycled aggregates in mortars, with their processing causing a reduction in their use in landfill, contributing to recycling and also minimizing the consumption of virgin materials. Although some research is currently being carried out into recycled mortars, little is known about their stress-strain (σ-ε); therefore this work will provide the experimental results obtained from recycled mortars with recycled ceramic aggregates (with contents of 0, 10, 20, 30, 50 and 100%), such as: the density, the compression strength, as well as the σ-ε curves representative of their behavior. The values obtained from the analysis process of the results are those of: σ (elastic ranges and failure maximum), ε (elastic ranges and failure maximum), and Resilience and Toughness; in order to finally obtain, through numerical analysis, the equations to predict their behavior (related to their recycled content). At the end of the investigation it is established that mortars with recycled ceramic aggregate contents of up to 20% could be assimilated just like mortars with the usual aggregates, and the prediction equations produced could be used in cases of similar applications.

Background: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR). Methods: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. Results: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3+4 groups, with the GOLD 1 group used as the reference [Hazard Ratio 4.222 (95% CI 1.298 - 13.733), p=0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3+4. The St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3+4, but not between STAR 1 and STAR 2. Conclusion: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

Background: COVID-19 pandemic has pulled us all a few steps back, were we never shake hands or hug each other when we meet our friends and family after a gap, but instead we greet them by saying Namaste and joining our hands together. As we all know, COVID-19 spreads through air and the only way to shield ourselves is by maintaining a safe distance from one another. Methodology: In order to conduct a meta-analysis on the number of COVID-19 cases in Kerala and India, the data was retrieved from various sites hosted by the government bodies. The data for analysis was collected from May 2020 to July 2020. The average number of days required to reach every 5000 fresh cases were also calculated using this data. COVID-19 has affected all the economy holistically regardless of financial, behavioral, or societal aspects. Conclusion: Lifting of the lockdown in a step by step process keeping in mind the necessities for the nation was a thoughtful act, but the people who mistook this opportunity and did not remain in quarantine after coming from abroad was recognized as the reasons behind the sudden and uncontrolled rise in the number of COVID-19 cases in Kerala, India. The government authorities had no other option but to lift the restrictions to reduce the economic burdens that had already affected the daily wage worker and farmers prompting them to give up their lives.

The goods and services produced by forest vegetation ecosystem are the driving force for the rapid, high-quality and sustainable development of human society. In history, with the increase of population and economic development, there is an increasing demand for the quantity and variety of forest vegetation ecosystem products and services in a country or a region. To meet the demands, most of the original forest has become farmland, plantation and grass and crops land. As a result, the plant water relationship changed from equilibrium to non-equilibrium, which easily led to soil drought, soil degradation and vegetation decline in dry years or waste of soil water in rainy years in most of water-limited regions. In order to solve the question and realize the sustainable utilization of soil water resources and the high-quality sustainable development of forest, it is necessary to apply the limit theory of plant utilization of soil water resources and the vegetation carrying capacity theory in the critical period of plant-water relationship regulation to adjust the relationship between plant growth and soil moisture to obtain the maximum yield and benefit and realize high-quality and sustainable development.

Safety limits application has always been a traditional approach to ensure the safe operation of electro-mechanical systems within many industries including automated vehicles, robotics, aerospace, traditional automotive, railways, manufacturing, etc. In all of these applications, control and safety limits are usually hard-coded into the production firmware and are fixed throughout the entire product life cycle. Currently, due to the evolving needs of automated systems like automated vehicles and robots, this traditional approach does not address all the use cases and scenarios to ensure safe operation. Especially for data-driven machine learning applications that constantly evolve and learn over time, it is important to be able to adjust the safety limits application strategy to be more flexible and adaptable based on different Operational Design Domains (ODDs) and scenarios. Our ITSC conference paper ~\cite{4} introduced the concept of a new safety limits application strategy called the Dynamic Control Limits Application (DCLA) strategy that supports the flexible application of diverse limits profiles based on the parameters involved within the dynamic scenario at different layers of the Autonomy software stack.This paper extends the DCLA strategy to derive the complete methodology for safety limits application based on ODD elements, scenario identification and scenario classification using Decision Making Engines. It leverages the layered architecture introduced in the ITSC conference paper to implement the Decision Making (DM) algorithms. Another important extension is the use of cloud infrastructure that is based on the Vehicle-to-Infrastructure (V2I) technology to store the scenarios and the limits mapping to serve as a ground truth and/or a backup mechanism in case of errors or failures associated with the main Decision Making (DM) Engine. There is also a focus on providing a more comprehensive list of scenarios and a custom built experimental dataset to cover the maximum ODD elements, and multiple tables of safety limits to be chosen from, which eventually helps in creating different safety limits application profiles. These distinct safety limits application profiles are based on the scenario parameters that are perceived by the system upon which the Decision Making algorithms are applied or trained. This systematic approach can be used within the industry for any of the future automated vehicles and systems until Level 5 Autonomy.

There is a balanced plant-water relationship in the primary vegetation of desert area. With the increase of population and social development in desert areas, people’s need for forest vegetation ecosystem’s goods and service have been changed. To meet the growing demand for plant community goods and services, more original vegetation has been changed into non-native vegetation such as in China loess plateau. However, with the plant growth, sometime soil drying happens and then becomes gradually serious with times in most of desert regions. Serious drying of soil eventually result in soil degradation, vegetation decline and agriculture failure，which influence the produce and supply of forest vegetation goods and service in market in dry year or waste of soil water resources in wet year, which wastes precious nature resources. In order to solve these problems, the soil water resources have to be used in sustainable way and plant-water relationship have to be regulated on Carrying Capacity of Soil Water for Vegetation in the key period of plant water relationship regulation, to carry out sustainable use of nature resources, high-quality and sustainable development of forest and grass or high-quality produce of fruit and crop in desert re-gions.

Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. Methods: We applied Motifs Co-Occurrence Tool (MCOT) that predicted pairs of spaced or overlapped motifs (composite elements, CEs) for a single ChIP-seq dataset. We improved MCOT capability for prediction of asymmetric CEs with one of participating motifs possessing higher conservation than another does. Results: Analysis of 119 ChIP-seq datasets for 45 human TFs revealed that almost for all families of TFs the co-occurrence with an overlap between motifs of target TFs and more conserved partner motifs was significantly higher than that for less conserved partner motifs. The asymmetry toward partner TFs was the most clear for partner motifs of TFs from ETS family. Conclusion: Co-occurrence with an overlap of less conserved motif of a target TF and more conserved motifs of partner TFs explained a substantial portion of ChIP-seq data lacking conserved motifs of target TFs. Among other TF families, conservative motifs of TFs from ETS family were the most prone to mediate interaction of target TFs with its weak motifs in ChIP-seq.

Let β= (((24!)!)!)!, and let {${\mathcal P}_{n^2+1}$} denote the set of all primes of the form {$n^2+1$}. Let ${\mathcal M}$ denote the set of all positive multiples of elements of the set {${\mathcal P}_{n^2+1} \cap (\beta,\infty)$}. The set {${\mathcal X}=\{0,\ldots,\beta\} \cup {\mathcal M}$} satisfies the following conditions: (1) ${\rm card}({\mathcal X})$ is greater than a huge positive integer and it is conjectured that ${\mathcal X}$ is infinite, (2)} we do not know any algorithm deciding the finiteness of ${\mathcal X}$, (3)~a~known and short algorithm for every {$n \in N$} decides whether or not {$n \in {\mathcal X}$}, (4) a known and short algorithm returns an integer~$n$ such that ${\mathcal X}$ is infinite if and only if ${\mathcal X}$ contains an element greater than $n$. The following problem is open: {\em simply define a set {${\mathcal X} \subseteq N$} such that ${\mathcal X}$ satisfies conditions (1)-(4), and \underline{we do not know any representation of~~${\mathcal X}$~~as a finite union of sets whose definitions are simpler than} \underline{the definition of ${\mathcal X}$}} {\tt (5)}. Let {$f(1)=2$}, {$f(2)=4$}, and let {$f(n+1)=f(n)!$} for every integer {$n \geqslant 2$}. For a positive integer $n$, let {$\Psi_n$} denote the following statement: {\em if a system of equations ${\mathcal S} \subseteq \Bigl\{x_i!=x_k: i,k \in \{1,\ldots,n\}\Bigr\} \cup \Bigl\{x_i \cdot x_j=x_k: i,j,k \in \{1,\ldots,n\}\Bigr\}$ has only finitely many solutions in positive integers \mbox{$x_1,\ldots,x_n$}, then each such solution \mbox{$(x_1,\ldots,x_n)$} satisfies {$x_1,\ldots,x_n \leqslant f(n)$}.} We prove that for every statement $\Psi_n$ the bound {$f(n)$} cannot be decreased. The author's guess is that the statements {$\Psi_1,\ldots,\Psi_9$} are true. We prove that the statement $\Psi_9$ implies that the set ${\mathcal X}$ of all {non-negative} integers $k$ whose number of digits belongs to {${\mathcal P}_{n^2+1}$} satisfies conditions {\tt (1)-(5)}.

The study of the emission, propagation, and reflection of balls in Newtonian mechanics, applying the laws of conservation of momentum and energy when the mass of the balls converges to zero, concludes that the kinematics of light are like those of massless balls. The kinematics of light explain why the speed of light is the constant c in each inertial frame in which the light source and reflective mirror are at rest, why the laws of physics have the same form in each inertial frame, and why any light experiment in an inertial frame cannot prove the motion of that inertial frame. The following law of mechanics governs the kinematics of balls and electromagnetic radiation: Each inertial frame drags at its velocity the balls and electromagnetic radiation emitted by bodies at rest in that inertial frame. The theory of special relativity misapplies the symmetry observed in phenomena to two inertial frames; therefore, it duplicates a physical phenomenon from one inertial frame, which is considered stationary, into another. There are multiple issues rooted in Lorentz's and Einstein's transformations. For example, transformations offer the speed of light at the constant c in the moving and opposite directions of the inertial frame. At the same time, it is variable in any other direction, converging to infinity. Time contraction in the moving direction of the inertial frame is different from time dilation in the opposite direction. It requires a ruler and time synchronization in each direction. There are no length contractions in Lorentz's and Einstein's transformations to support the fundamental concept of length contraction in special relativity. With these unacceptable conclusions, the theory of special relativity is self-negating.

SARS-CoV-2 Omicron variant spike RBD epitopes in complex with spike (S) -protein D614G mutations now predominate globally and increase infectivity by assembling more functional S proteins into the virion. On average, homeopathic medicine contains less than one molecule per dose on average. Single variable SphericalHarmonicY, LaguerreL, WhittakerM, SphericalBesselJ, LegendreP, LegendreQ, LaguerreL, ChebyshevT, and Hypergeometric1F1 Functions pFqarise in connection with the power series solution of the Schrodinger equation or in the summation of perturbation expansions in quantum mechanics. A quantum interpretation of the homeopathic method is presented here through a novel algebraic topology approach to supersymmetry and symmetry breaking in quantum fields and quantum gravity theory with the aim of developing a wide range of physical-based drug design applications in a Small Molecule Quantized Water Memory Network suggesting that the Hidden Black Hole Paradox of Information Loss might be solved under suitable conditions.

There are many molecules used as drug carrier. TUD-1 is a newly synthesized mesoporous silica (SM) molecule possess two important features; consists of mesoporous so it is very suitable to be drug carrier in addition to that it has the ability to induce apoptosis in cancer cells. However, the effect of TUD-1 appears to act as cell death inducer, regardless of whether it is necrosis or apoptosis. Unfortunately, recent studies indicate that a proportion of cells undergo necrosis rather than apoptosis, which limits the use of TUD-1 as a secure treatment. On the other hand, lithium considered as necrosis inhibitor element. Hence, current study based on the idea of production a new Li/TUD-1 by incorporated mesoporous silica (TUD-1 type) with lithium in order to produce a new compound that has the ability to activate apoptosis by mesoporous silica (TUD-1 type) and at the same time can inhibit the activity of necrosis by lithium. Herein, lithium was incorporated in TUD-1 mesoporous silica by using sol-gel technique in one step synthesis procedure. Moreover, lithium was incorporated in TUD-1 with different loading in order to form different active sites such as isolated lithium ions, nanoparticles of Li2O, and bulky crystals of Li2O. The ability of the new compounds to induce apoptosis and prevent necrosis was evaluated on three different types of cancer cell lines which are; liver HepG-2, Breast MCF-7 and colon HCT116. The obtained results show that Li/TUD-1has the ability to control necrosis and thus reduce the side effects of treatments containing silica in the case of lithium has been added to them, especially in chronic cases. This has been demonstrated by the significant increase in the IC50 value and cell viability comparing to control groups. Consequently, the idea is new, so it definitely needs more develop and test with materials that have more apoptotic impact than silica in order to induce apoptosis without induction of necrosis.

Leishmaniases are zoonotic vector-borne diseases caused by a wide variety of Leishmania species with complex transmission cycles involving different reservoirs, potential new hosts and vectors. Similarly, to other eukaryotes, Leishmania release extracellular vesicles (LEVs) to play important initial interactions that are crucial to modulate the subsequent systemic immune response on the establishment of infection in humans and others hosts like dogs. Recent studies in endemic areas of Brazil concluded that canine infections were predominantly due to L. amazonensis and not restricted to L. infantum (syn. Leishmania chagasi). Under these premises, the diagnosis of leishmaniasis needs to be improved with the identification of current etiological agent and the histopathologic features, highlighting the differential diagnosis and the molecular components of LEVs. In this way, the dual aim of that study is to register collected observations of natural canine infections, enhancing the relevance of differential diagnosis in companion animals and inserting in vitro results in the field of LEVs that still research gaps to be filled to understand the mechanisms and biological aspects involving the parasite-host interactions. Therefore, improve these studies of Parasitology research is important for diagnostic, prognostic, treatment advances and continuing need for global prevention, control, elimination/eradication of these parasitic infections.

The last 50 years witnessed the emergence of various so called “hyperpolarization technologies” that allow generating large magnetizations of spin ensembles. This Editorial Essay provides a brief overview of the use of these technologies in various fields, including medicine, chemistry, and quantum sensing. It is concluded that critical questions still need to be addressed to harness benefits of nuclear hyperpolarization in clinical medical imaging while interdisciplinary innovation can unlock potential of novel (yet unexplored) methods. My hope is that this Editorial Essay provides valuable insights into the current state and future directions of spin technologies.

Abstract:Shown is the derivation of Lorentz-Einstein k-factor in SRT as an amplitude-term of oscillation-differential equations of second order.This case is shown for classical Lorentz-factor as solution of an equation for undamped oscillation as well as the developed theorem as a second solution for advanced SRT of fourth order with an equation for damped oscillation-states.This advanced term allows a calculation for any velocities by real rest mass