CBCR: A Curriculum Based Strategy For Chromosome Reconstruction

In this paper, we introduce a novel algorithm that aims to estimate chromosomes’ structure from their Hi-C contact data, called Curriculum Based Chromosome Reconstruction (CBCR). Specifically, our method performs this three dimensional reconstruction using cis-chromosomal interactions from Hi-C data. CBCR takes intra-chromosomal Hi-C interaction frequencies as an input and outputs a set of xyz coordinates that estimate the chromosome’s three dimensional structure in the form of a .pdb file. The algorithm relies on progressively training a distance-restraint-based algorithm with a strategy we refer to as curriculum learning. Curriculum learning divides the Hi-C data into classes based on contact frequency and progressively re-trains the distance-restraint algorithm based on the assumed importance of each curriculum in predicting the underlying chromosome structure. The distance-restraint algorithm relies on a modification of a Gaussian maximum likelihood function that scales probabilities based on the importance of features. We evaluate the performance of CBCR on both simulated and actual Hi-C data and perform validation on FISH, HiChIP, and ChIA-PET data as well. We also compare the performance of CBCR to several current methods. Our analysis shows that the use of curricula affects the rate of convergence of the optimization while decreasing the computational cost of our distance-restraint algorithm. Also, CBCR is more robust to increases in data resolution and therefore yields superior reconstruction accuracy of higher resolution data than all other methods in our comparison.     

Modular supply chain optimization considering demand uncertainty to manage risk

Supply chain under demand uncertainty has been a challenging problem due to increased competition and market volatility in modern markets. Flexibility in planning decisions makes modular manufacturing a promising way to address this problem. In this work, the problem of multiperiod process and supply chain network design is considered under demand uncertainty. A mixed integer two-stage stochastic programming problem is formulated with integer variables indicating the process design and continuous variables to represent the material flow in the supply chain. The problem is solved using a rolling horizon approach. Benders decomposition is used to reduce the computational complexity of the optimization problem. To promote risk-averse decisions, a downside risk measure is incorporated in the model. The results demonstrate the several advantages of modular designs in meeting product demands. A pareto-optimal curve for minimizing the objectives of expected cost and downside risk is obtained.     

A mathematical modeling approach for supply chain management under disruption and operational uncertainty

In this work, we proposed a two-stage stochastic programming model for a four-echelon supply chain problem considering possible disruptions at the nodes (supplier and facilities) as well as the connecting transportation modes and operational uncertainties in form of uncertain demands. The first stage decisions are supplier choice, capacity levels for manufacturing sites and warehouses, inventory levels, transportation modes selection, and shipment decisions for the certain periods, and the second stage anticipates the cost of meeting future demands subject to the first stage decision. Comparing the solution obtained for the two-stage stochastic model with a multi-period deterministic model shows that the stochastic model makes a better first stage decision to hedge against the future demand. This study demonstrates the managerial viability of the proposed model in decision making for supply chain network in which both disruption and operational uncertainties are accounted for.     

Effect of preprocessing techniques on pearl millet flour and changes in technological properties

This study investigated the effect of some preprocessing techniques on the physicochemical and technological properties of pearl millet flour for possible industrial application. Pearl millet was processed into flour using different preprocessing techniques (blanching, debranning, fermentation and malting) and evaluated for physicochemical and functional properties, grain morphology and total viable count. The result showed that fermentation and malting brought about loosening of starch granules. Fermentation significantly reduced the bulk density by 22% and improved the colour lightness and paste viscosity properties of the preprocessed flour. Malting alone resulted in about 50% increase in protein content of the flour with improved solubility up to 64 g/100 g. Total viable count was highest in fermented sample in the order of 10⁸ cfu g^?1. Thus, the combination of fermentation and malting would give the best pearl millet flour with improved technological properties for application in the industries, thereby promoting food security in the region.     

The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis

While cardiovascular disease (CVD) is the leading cause of death, major depressive disorder (MDD) is the primary cause of disability, affecting more than 300 million people worldwide. Interestingly, there is evidence that CVD is more prevalent in people with MDD. It is well established that neurotransmitters, namely serotonin and norepinephrine, are involved in the biochemical mechanisms of MDD, and consequently, drugs targeting serotonin-norepinephrine reuptake, such as duloxetine, are commonly prescribed for MDD. In this connection, serotonin and norepinephrine are also known to play critical roles in primary hemostasis. Based on these considerations, we investigated if duloxetine can be repurposed as an antiplatelet medication. Our results-using human and/or mouse platelets show that duloxetine dose-dependently inhibited agonist-induced platelet aggregation, compared to the vehicle control. Furthermore, it also blocked agonist-induced dense and α-granule secretion, integrin αIIbβ3 activation, phosphatidylserine expression, and clot retraction. Moreover duloxetine-treated mice had a significantly prolonged occlusion time. Finally, duloxetine was also found to impair hemostasis. Collectively, our data indicate that the antidepressant duloxetine, which is a serotonin-norepinephrine antagonist, exerts antiplatelet and thromboprotective effects and inhibits hemostasis. Consequently, duloxetine, or a rationally designed derivative, presents potential benefits in the context of CVD, including that associated with MDD.     

Probiotic potentials of cereal-based beverages

Probiotics offer remarkable potential for the prevention and management of various infective and noninfective disorders. They are reported to play key roles in the suppression of gastrointestinal infections, antimicrobial activity, improvement in lactose metabolism, reduction in serum cholesterol, immune system stimulation, antimutagenic properties, anticarcinogenic properties, anti-diarrheal properties, and improvement in inflammatory bowel disease. Although probiotic foods are classically confined to beverages and cheese, containing live organisms of the lactic acid bacteria family, such health-promoting foods are traditionally dairy-based, comprising milk and its fermented products. However, recent research focuses on the probiotic potentials of fermented cereal-based beverages which are especially consumed in developing countries characterized by low nutritional security and high incidence of gut pathogen infections. Moreover, lactose intolerance and cholesterol content associated with dairy products, coupled with the vegetarian tendencies of diverse populations in the third world, tend to enforce the recent recourse to nondairy beverages. Probiotic microorganisms are mostly of human or animal origin; however, strains recognized as probiotics are also found in nondairy fermented substrates. This review examines the potentials of some traditional cereal-based beverages to serve as probiotic foods, their microbial and functional properties, as well as their process optimization and storage for enhanced utilization.     

Vulnerability of hand-dug wells in the core area of Akure,Nigeria

Hand-dug wells (HDWs) are a major source of water supply in developing nations. This is consequent upon the failure of government to provide safe water to the people. This paper looks at the vulnerability of HDWs in the core area of Akure, Nigeria. The study area is made up of 11 residential quarters with 1149 buildings; 10% of buildings and five wells in each quarter were randomly selected for the study. Data were collected using structured questionnaires and laboratory examinations. Water quality assessment showed that most parameters fall within WHO permissible limits for drinking water. However, microbial examinations indicated that drinking water quality was compromised in two residential quarters as there was evidence of coliform and e-coli. The study also identified other possible sources of water contamination in the study area. This paper recommends regular treatment of wells and the adoption of pipe-borne water supply systems in the city and other similar cities in developing countries.     

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC₅₀ = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC₅₀ = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.     

Physicochemical and sensory attributes of gluten-free sourdough breads produced from underutilised African cereal flours and flour blends

To seek potential alternative(s) for imported wheat in the African baking industry, the physicochemical parameters and sensory attributes of sourdough breads developed from locally sourced underutilised cereals and their blends were assessed. Processed sorghum (Sorghum bicolour), finger millet (Eleusine coracana) and pearl millet (Pennisetum glaucum) and their composites (50:50) were used to produce sourdough. Sourdough and flour-sourdough blends (30% sourdough) were used in making gluten-free breads. The protein content of the breads ranged from 16.29% to 39.26%, whereas the fat, crude fibre, ash and carbohydrate contents fell between 14.02–18.80%, 0.55–1.22%, 1.90–3.32% and 42.16–65.61%, respectively. The calculated energy value of the gluten-free breads (405.99–446.39 Kcal per 100 g) exceeded that of wheat bread (396.43 Kcal per 100 g), while the specific loaf volume varied from 1.46 to 1.80 cm³ g⁻¹. Although the produced gluten-free breads have improved nutritional content compared to conventional wheat bread, they were at best moderately liked. This is perhaps due to the non-cohesive nature of the crumbs and psychological preference for known products. Further research targeted at improving the organoleptic properties of these sourdough breads is recommended.