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In this paper, we use the dataset of a marine berthing structure per hour to construct the objective and linear constraint functions from the combination of a simple and non-preemptive queuing model, and we determine the optimal design of vessels and layout of quay through the solutions of quadratic programming problems. A methodology is proposed to formulate the quadratic programming problems from the input and output data of the mixed queuing model as the constraints on the characteristics of logistic demand, service time, waiting time, vessels, and layout of service quay for minimum utilization cost. This approach is applied to the port authority of Kribi in the south region of Cameroon to examine the more precise optimal solution with nonlinear complexities in the programs of discrete computer simulations. With adaptive experimental data of the modelling of berths as mixed models, the results provide the value of the most optimal solution projected in the port of Kribi compared to the solutions of integer and traditional linear programming problems. This study delivers the optimal number of vessel types and the associated layout in order of importance among the vessel types which can be safely moored for operations.

Naturalizing plants are characterized by both a reduction in the gene pool in comparison with the genetic diversity of the same species in the natural range, and the accumulation of new adaptive traits. Nanking cherry (Prunus tomentosa Thunb.) on the one hand, it demonstrates instability to support in the conditions of Yekaterinburg, on the other hand, it shows a tendency to naturalize in the vicinity of Chelyabinsk. The study of the variability of plants in the places of naturalization of Nanking cherry by weight, fruit color, and peduncle length showed that the value of such populations for the selection of new selected forms is not inferior to the breeding garden laid from seedlings obtained from free pollination in varietal plantations of Nanking cherries. Only plants that have undergone natural selection in nature can be characterized by a higher adaptive potential. The range of variability in fruit weight for all studied plants in naturalization sites ranged from 0.57 to 2.16 g. In the breeding garden – from 0.62 to 2.20 g. Among the varieties, the highest average fruit weight in 2021 was noted for the Natalie variety 4.1 g, but in previous and subsequent years of observations did not reach such values. In the naturalizing populations, no plants with the maroon color of the fruit characteristic of the Damanka variety were found. In the breeding garden, such a fruit color was found, but the weight of the fruit is much less than that of the Damanka variety. The varieties, including some of which were obtained by introgressive hybridization with the species of Nanking cherry and louisiania vicinifolia (Louiseania ulmifolia (Franch.) Pachom. sin. Prunus ulmifolia Franch.), did not show an increase in the length of the peduncle, characteristic of the species that took part in the creation of varieties. Plants with a longer peduncle length than those of existing varieties were found at individual centers of naturalization.

Background: Consumption coagulopathy and hemorrhagic syndrome are the typical features of Bothrops sp. snake envenoming. In contrast, B. lanceolatus envenoming can induce thrombotic complications. Our aim was to test whether crude B. lanceolatus and B. atrox venoms would display procoagulant activity and induce thrombus formation under flow conditions. Methods and Principal Findings: Fibrin formation in human plasma was observed for B. lanceolatus venom at 250–1000 ng/mL concentrations, which also induced clot formation in purified human fibrinogen, indicating thrombin-like activity. The degradation of fibrinogen confirmed the fibrinogenolytic activity of B. lanceolatus venom. B. lanceolatus venom displayed consistent thrombin-like and kallikrein-like activity increases in plasma conditions. The well-known procoagulant B. atrox venom activated plasmatic coagulation factors in vitro and induced firm thrombus formation under high shear rate conditions. In contrast, B. lanceolatus venom induced the formation of fragile thrombi that could not resist shear stress. Conclusions: Our results suggest that crude B. lanceolatus venom displays amidolytic activity and can activate the coagulation cascade, leading to prothrombin activation. B. lanceolatus venom induces the formation of an unstable thrombus under flow conditions, which can be prevented by the specific monovalent antivenom Bothrofav®.

Abstract Monoterpene indole alkaloids (MIAs) are a structurally diverse family of specialized metabolites mainly produced in Gentianales to cope with environmental challenges. Due to their pharmacological properties, the biosynthetic modalities of several MIA types have been elucidated but not that of the yohimbanes. Here, we combine metabolomics, proteomics, transcriptomics and genome sequencing of Rauvolfia tetraphylla with machine learning to discover the unexpected multiple actors of this natural product synthesis. We identify a medium chain dehydrogenase/reductase (MDR) that produces a mixture of four diastereomers of yohimbanes including the well-known yohimbine and rauwolscine. In addition to this multifunctional yohimbane synthase (YOS), an MDR synthesizing mainly heteroyohimbanes and the short chain dehydrogenase vitrosamine synthase also display a yohimbane synthase side activity. Lastly, we establish that the combination of geissoschizine synthase with at least three other MDRs also produces a yohimbane mixture thus shedding light on the complex mechanisms evolved for the synthesis of these plant bioactives.

In this paper, we compare computational design of box culverts using Kleinlogel’s formulas and three-dimensional models based on Winkler and Modified Vlasov Foundation (MVF) by Radial Point Interpolation method (RPIM) . In order to extend the RPIM to the study of box culverts, a method of decomposition by subdomain and a creation of a fictitious rotation is made. Similar results are observed between the RPIM_Winkler and STAAD PRO (FEM software) with fewer nodes in the case study. The Kleinlogel’s formulas or the Winkler model gives a maximal increase in stresses at the middle of the raft of 5%, and a 12 times increased displacement. Finally, it emerges that for the same type of soil and a single structure, the reaction and shear modulus of the soil are highly dependent on the distribution of loads on the structure.

The article deals with the essence of migration processes in various theoretical concepts, as well as existing approaches to assessing the impact of labor migration on the state and functioning of the labor market. The author has made a scientific assumption about the need to assess the dependence of the scale of labor migration on socio–economic factors of the country or region, such as the level of economic development, the level of availability of medical and social services, the level of material well–being, the level of spiritual development.It is assumed that these factors are determined by statistical indicators for the region and should be ranked by an expert survey. Migration assessment makes it possible to predict the number and directions of migration flows and to develop measures of state influence and priorities of migration policy that ensures the economic and national security of the country.

PurposeOutpatients with hematologic disease often receive red cell transfusion to treat anemia and fatigue. The effect of transfusion on fatigue-related quality of life and how well this effect is sustained has not been quantified. The study aim was to describe the early and sustained impact over 4 weeks of red cells on patient-reported fatigue in outpatients age ≥ 50 receiving transfusion as routine clinical care.MethodsFACIT-Fatigue scale scores were measured pre-transfusion and at visits targeting 3, 7, and 28 days post-transfusion. Group-based trajectory modeling of patient fatigue scores by study day was used to identify the number of distinct trajectories (Groups), then longitudinal mixed effects modeling of fatigue scores was used to estimate group-specific mean improvements early after transfusion and between days 3 and 28 post-transfusion.ResultsFour distinct fatigue score trajectory groups were identified and were found to be correlated with baseline fatigue scores (means 12, 26, 34, and 47 points). In the three groups with the lowest fatigue trajectories (indicating greater fatigue), improvements in fatigue early after transfusion achieved the established minimum clinically important difference (≥ 3 points, Group p = 0.0039). In all trajectory groups, mean fatigue levels did not change significantly between 3 and 28 days (± 1 point, Group p = 0.60).ConclusionPatient-reported fatigue varies widely among older adult outpatients with hematologic disorders. Nonetheless, trajectory modeling suggests that most anemic patients can expect a noticeable improvement in fatigue in the first few days after transfusion that generally is sustained up to 4 weeks.

BackgroundRecent publications have reported conflicting findings regarding associations of blood donor demographics and mortality of transfused patients. We hypothesized that the analysis of additional donor characteristics and consideration of alternative outcomes might provide insight into these disparate results.Study design and methodsWe analyzed data from a retrospective cohort of transfused patients from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). We used stratified Cox regression models to estimate associations between blood donor characteristics and hospital mortality and posttransfusion length of stay among patients transfused red blood cell (RBC) units. Donor characteristics evaluated included age, body mass index, hemoglobin levels, and smoking status. The statistical analyses were adjusted for recipient factors, including total number of transfusions.ResultsWe studied 93,726 patients in 130,381 hospitalizations during which 428,461 RBC units were transfused. There were no associations between blood donor characteristics and hospital mortality. Receipt of RBC units from donors less than 20 years of age was associated with a shorter hospital length of stay (hazard ratio for discharge per transfused unit, 1.03; 95% confidence interval, 1.02-1.04; p

BACKGROUND:Patients with cancer or other diagnoses associated with chronic anemia often receive red blood cell (RBC) transfusion as outpatients, but the effect of transfusion on functional status is not well demonstrated. STUDY DESIGN AND METHODS:To estimate the effect of transfusion on functional status and quality of life, we measured 6-minute walk test distance and fatigue- and dyspnea-related quality-of-life scores before and 1 week after RBC transfusion in 208 outpatients age ≥50 with at least one benign or malignant hematology/oncology diagnosis. To account for potential confounding effects of cancer treatment, patients were classified into two groups based on cancer treatment within 4 weeks of the study transfusion. Minimum clinically important improvements over baseline were 20 meters in walk test distance, 3 points in fatigue score, and 2 points in dyspnea score. RESULTS:The median improvement in unadjusted walk test distance was 20 meters overall and 30 meters in patients not receiving recent cancer treatment. Fatigue scores improved overall by a median of 3 points and by 4 points in patients without cancer treatment. There was no clinically important change in dyspnea scores. In multiple linear regression analysis, patients who maintained hemoglobin (Hb) levels of 8 g/dL or greater at 1 week posttransfusion, who had not received recent cancer treatment, and who did not require hospitalization during the study showed clinically important increases in mean walk test distance. CONCLUSIONS:Red blood cell transfusion is associated with a modest, but clinically important improvement in walk test distance and fatigue score outcomes in adult hematology/oncology outpatients.

Background. Generation of a consistent base of fuzzy production rules is an important task, but no less important is the task of determining the most efficient generation algorithm. The purpose of this work is to research the effectiveness of six algorithms for generating a base of fuzzy production rules for the Wang-Mendel neural network using the example of solving a classification problem. Materials and methods. All researches werecarried out in the environment of the developed application, in which the software model of the Wang-Mendel network is implemented. The following algorithms have been studied for generating the rule base: an adaptive learning algorithm, the Abe-Len algorithm, a rating algorithm for generating fuzzy production rules, C-Means and C-Ellipses clustering algorithms, and new hybrid algorithm proposed in this paper and based on the Abe-Len algorithm and the rating algorithm. The researches have been done on the basis of four model data sets from the UCI repository: Fisher irises, types of wine drinks, types of breast cancer, and «Space Shuttle» data. Results. The research showed that the hybrid Abe-Len algorithm in combination with the rating algorithm and by the C-Ellipse clustering algorithm provides the best results. At the same time, the C-Ellipse algorithm assumes a manual preliminary selection of the optimal number of clusters, while this is not required in the proposed modification of the Abe-Len algorithm. Conclusions. The conducted research and implemented algorithms made it possible to obtain numerical estimates of the error in solving the classification problem and justify the choice of the most effective algorithms for generating a fuzzy rule base. The combination of the Abe-Len algorithms and the rating algorithm provides the maximum efficiency on the taken data sets.

SUMMARY: Plant‐specialized metabolism represents an inexhaustible source of active molecules, some of which have been used in human health for decades. Among these, monoterpene indole alkaloids (MIAs) include a wide range of valuable compounds with anticancer, antihypertensive, or neuroactive properties. This is particularly the case for the pachysiphine derivatives which show interesting antitumor and anti‐Alzheimer activities but accumulate at very low levels in several Tabernaemontana species. Unfortunately, genome data in Tabernaemontanaceae are lacking and knowledge on the biogenesis of pachysiphine‐related MIAs in planta remains scarce, limiting the prospects for the biotechnological supply of many pachysiphine‐derived biopharmaceuticals. Here, we report a raw version of the toad tree (Tabernaemontana elegans) genome sequence. These new genomic resources led to the identification and characterization of a couple of genes encoding cytochrome P450 with pachysiphine synthase activity. Our phylogenomic and docking analyses highlight the different evolutionary processes that have been recruited to epoxidize the pachysiphine precursor tabersonine at a specific position and in a dedicated orientation, thus enriching our understanding of the diversification and speciation of the MIA metabolism in plants. These gene discoveries also allowed us to engineer the synthesis of MIAs in yeast through the combinatorial association of metabolic enzymes resulting in the tailor‐made synthesis of non‐natural MIAs. Overall, this work represents a step forward for the future supply of pachysiphine‐derived drugs by microbial cell factories. [ABSTRACT FROM AUTHOR]

Despite its major role in the Earth’s climate regulation, the evolution of high-latitude ocean dynamics through geological time remains unclear. Around Antarctica, changes in the Southern Ocean (SO) circulation are inferred to be responsible for cooling from the late Eocene and glaciation in the early Oligocene. Here, we present a geochemical study of foraminifera from DSDP Site 277 (Campbell Plateau), to better constrain thermal and redox evolution of the high latitude southwest Pacific Ocean during this time interval. From 56 to 48 Ma, Mg/Ca- and δ18O-paleothermometers indicate high surface and bottom water temperatures (24–26°C and 12–14°C, respectively), while weak negative Ce anomalies indicate poorly oxygenated bottom waters. This is followed by a cooling of ∼4° between 48 and 42 Ma, possibly resulting from a weakening of a proto-EAC (East Australian Current) and concomitant strengthening of a proto-Ross gyre. This paleoceanographic change is associated with better ventilation at Site 277, recorded by an increasing negative Ce anomaly. Once this proto-Ross gyre was fully active, increasing biogenic sedimentation rates and decreasing Subbotina sp. δ13C values indicate enhanced productivity. This resulted in a shoaling of the oxygen penetration in the sediment pile recorded by increasing the foraminiferal U/Ca ratio. The negative Ce anomaly sharply increased two times at ∼35 and ∼31 Ma, indicating enhanced seawater ventilation synchronously with the opening of the Tasmanian and Drake Passage gateways, respectively. The Oligocene glaciation is recorded by a major increase of bottom seawater δ18O during the EOT (Eocene-Oligocene Transition) while Mg/Ca-temperatures remain rather constant. This indicates a significant ice control on the δ18O record.

Background: Consumption coagulopathy and hemorrhagic syndrome are the typical features of Bothrops sp. snake envenoming. In contrast, B. lanceolatus envenoming can induce thrombotic complications. Our aim was to test whether crude B. lanceolatus and B. atrox venoms would display procoagulant activity and induce thrombus formation under flow conditions. Methods and Principal Findings: Fibrin formation in human plasma was observed for B. lanceolatus venom at 250–1000 ng/mL concentrations, which also induced clot formation in purified human fibrinogen, indicating thrombin-like activity. The degradation of fibrinogen confirmed the fibrinogenolytic activity of B. lanceolatus venom. B. lanceolatus venom displayed consistent thrombin-like and kallikrein-like activity increases in plasma conditions. The well-known procoagulant B. atrox venom activated plasmatic coagulation factors in vitro and induced firm thrombus formation under high shear rate conditions. In contrast, B. lanceolatus venom induced the formation of fragile thrombi that could not resist shear stress. Conclusions: Our results suggest that crude B. lanceolatus venom displays amidolytic activity and can activate the coagulation cascade, leading to prothrombin activation. B. lanceolatus venom induces the formation of an unstable thrombus under flow conditions, which can be prevented by the specific monovalent antivenom Bothrofav®. [ABSTRACT FROM AUTHOR]

Background. Studying genetic polymorphism of the Prunus pumila L. representatives with a wide range of variability in morphological characters will make it possible to identify promising genotypes with high combining ability for hybridization.Material and methods. The study covered 39 genotypes from the Chelyabinsk cultivated population and 6 genotypes from Khakassia, with extreme or intermediate expressions of such characters as fruit size, color and shape; stone shape and surface structure; leaf blade serration and shape; plant habitus, and some others. Genetic distances were calculated using the data matrix for binary states of presence (1) or absence (0) of amplified fragments with the Past Program (Gower). The UPGMA dendrograms were obtained in TREECON (version 1.3b).Results and discussion. The selected 5 ISSR and 2 RAPD primers demonstrated their effectiveness in detecting genetic polymorphism in the studied accessions. In individual cases, a weak connection of separate markers with leaf blade edge serration, stone surface structure, plant habitus, and geographic origin of the genotype was detected. Concurrent inclusion of all primers and genotypes in the cluster analysis failed to group the studied P. pumila samples into clades according to the presence/absence of any traits, which may attest to their close genetic affinity. An independent clade with reliable bootstrap support (100%) was formed only for the genotypes of the taxonomically close sp. P. tomentosa Thunb., analyzed as an external group. Moreover, this clade manifested (with the 86% reliability of bootstrap support) differences between the hybrid genotypes of P. pumila × P. tomentosa (F3) and the genotype of P. tomentosa. Parent pairs promising for fruit quality and shrub shape improvement through breeding were identified using the produced indices of genetic distinction.

A collaborative at several sites across the state of California will offer evidence of how successful linked learning, which connects academics to real-world work, can be. This article presents examples that illustrate the powerful connections and linkages that are generated by combining academic rigor with the relevance of applying learning to real-world work and careers. The connection is compelling not only to students, but to teachers, industry, and funders as well. The article also presents highlights that describe challenges, successes, and lessons learned from the work of the Alliance for Regional Collaboration to Heighten Educational Success (a statewide organization) with six regional collaboratives as they plan and implement linked learning approaches in specific school sites, with the support of the Irvine Foundation.

Background. The studied population of Prunus pumila L. has been introduced into Chelyabinsk Province, as its natural area of distribution is in North America. Of interest for researchers is the introduced population’s variability, induced by the effect of soil and climate factors natural for its new habitat.Materials and methods. A collection of 197 plants was employed to study the variability of P. pumila. Morphological characters were described in compliance with atlases dedicated to seed and fruit descriptive morphology, with some adjustments concerning specific features of the subfamily Prunoideae Focke. The confidence interval for means was calculated using the reliability criterion of t2 = 2.576. The degree of variation was assessed for the studied characters according to S. A. Mamaev’s scale.Results and conclusion. The average fruit weight was 2.49±0.11 g and varied from 1.25 to 5.15 g. The average stone weight was 0.25±0.01 g. Out of the number of morphometric traits, almost all linear characters of fruit and stone size had low variability (coefficient of variation [V]: 8–12%). Of those linear characters, only the peduncle length showed medium variability (V = 13–20%). The stone weight also had medium variability, while the fruit weight demonstrated high variability (V = 21–30%). The fruit shape was subglobose (40.3%), less frequently ovate (20.9%), ovoid (20.9%), broadly ovoid (9.7%), cordate (6.1%) or elliptic (2.0%). The ventral suture was usually barely noticeable, less frequently moderately (3.1%) or strongly expressed (1.0%). Polymorphism was observed in the pulp color, which was usually green-pink (72.8%). The P. pumila stone shape was elliptic (38.1%) or subglobose (34.0%), less frequently prolate (10.7%), ovoid (13.2%) or obovate (4.1%). The stone was symmetrically shaped from the ventral suture and sides, usually looking subglobose from the sides. The shape of the stone’s apex was rounded (85.3%) or, less frequently, obtusely mucronate (15.7%); its base was rounded (80.7%), often attenuate (15.7%), less frequently slightly slanted (3.6%). The stone surface texture was smooth (57.4%), often slightly costate (36.5%). There were several cases of a more costate surface of the stone (6.1%). Thus, the introduced population was found to have broad polymorphism of morphological characters in the fruit and the stone. A considerable increase was observed in morphometric indicators, including the size of fruit and stone, compared with those typical for the species in natural environments, which may be of special significance for breeders. The fusiform shape of the stone, characteristic of var. depressa Pursh. in its natural habitat, was absent in the introduced population.

Mesenchymal stem cells (MSCs) have drawn lots of attention as gold standard stem cells in fundamental and clinical researches during the last 20 years. Due to their tissue and vascular repair capacities, MSCs have been used to treat a variety of degenerative disorders. Moreover, MSCs are able to modulate immune cells’ functions, particularly T cells while inducing regulatory T cells (iTregs). MSCs are very sensitive to inflammatory signals. Their biological functions could remarkably vary after exposure to different pro-inflammatory cytokines, notably TNFα. In this article, we have explored the importance of TNFR2 expression in a series of MSCs’ biological and functional properties. Thus, MSCs from wild-type (WT) and TNFR2 knockout (TNFR2 KO) mice were isolated and underwent several ex vivo experiments to investigate the biological significance of TNFR2 molecule in MSC main functions. Hampering in TNFR2 signaling resulted in reduced MSC colony-forming units and proliferation rate and diminished the expression of all MSC characteristic markers such as stem cell antigen-1 (Sca1), CD90, CD105, CD44, and CD73. TNFR2 KO-MSCs produced more pro-inflammatory cytokines like TNFα, IFNγ, and IL-6 and less anti-inflammatory mediators such as IL-10, TGFβ, and NO and induced Tregs with less suppressive effect. Furthermore, the TNFR2 blockade remarkably decreased MSC regenerative functions such as wound healing, complex tube formation, and endothelial pro-angiogenic support. Therefore, our results reveal the TNFα–TNFR2 axis as a crucial regulator of MSC immunological and regenerative functions.

The optimal design of a twenty-five bar space truss commonly involves multiple loading conditions acting on 4 node elements in the linear elastic model. In this paper, we describe the behavior of the truss system with our experimental loading conditions on five node elements subject to minimum displacement and stresses that are used to formulate the constrained nonlinear optimization problem. Numerical computations are developed with the objective of mass minimization and the best structural design is selected by applying the interior point method with the guidance of Matlab Optimization Toolbox. Our numerical results show the optimal values of cross-sectional areas, material densities, and internal forces which satisfy the minimum weight design. These results provide the appropriate mass to the experimental data and allow substantial changes in size, shape, and topology.

Yam (Dioscorea spp.) is a staple food crop and a source of income for millions of people in West Africa. Traditionally, in West Africa, yams are grown without any external inputs, leading to low tuber yields. The rapid decrease of tuber yield observed after the first yam cropping season has been ascribed to nutrient depletion and/or to the accumulation of yam-specific pests and diseases. This has led farmers to grow yam on new surfaces under fallow each year. Using a transdisciplinary approach, we identified different yam-based rotations and fertilization regimes that could stabilize yam production in rotational cropping systems and improve water yam (D. alata) productivity. These innovations were tested in researcher-managed field trials established along an environmental gradient crossing four yam growing zones spanning from the Humid Forest (Liliyo in Côte d’Ivoire) to the Derived Savanna/Forest Transition (Tiéningboué in Côte d’Ivoire), the Southern Guinean Savanna (Midebdo in Burkina Faso), and the Northern Guinean Savanna (Léo in Burkina Faso) between 2016 and 2018. The fertilization factor implemented at each site included a control with no fertilization (NON), sole mineral fertilization as NPK (MIN), combined organic and mineral fertilization (MINORG) and sole organic fertilization as manure (ORG), while the rotation factor included water yam in rotation with cereal (YamCer), legume (YamLeg), and white yam (YamYam). The average water yam tuber yields were 32.8, 20.3, 2.7, and 2.5 t fresh matter ha−1 in 2016, and 16.4, 10.7, 8.9, and 5.2 t fresh matter ha−1 in 2018 in Liliyo, Tiéningboué, Midebdo, and Léo, respectively. The most important determinants of tuber yields were the total amount of rainfall recorded during the yam growing period and between tuber initiation and maximum canopy development, and the soil carbon stocks in the 0–30-cm layer. We confirmed in this study that soil surface coverage measured between 70 and 98 days after planting was an early indicator of tuber yield. Fertilization impacted positively the soil surface cover but had a weak impact on tuber yields. Rotation had no impact on either the soil surface cover or tuber yields. This lack of observable impacts was partly due to the very large variability of tuber yields, to the variable rainfall, and to an anthracnose attack in two sites in 2018. The impacts of fertilization and rotation on yam yields should be studied over longer periods. This is, to our knowledge, the first publication showing the relative impacts of site-specific properties (rainfall and soil carbon stocks) versus management practices on water yam yield along an environmental gradient going across the West African yam belt.