Kidney Injuries in Sickle Cell Disease

Sickle cell disease (SCD), characterized by the presence of unstable sickle hemoglobin in the homozygous state (HbSS), results in progressive organ damage and early mortality with the median age of death in the 40s. The kidney is one of the most severely affected organs in SCD. Kidney diseases gradually develop in individuals with SCD. Microalbuminuria is evident in childhood, progressing to apparent proteinuria, deteriorating glomerular filtration rate (GFR) in early adulthood. While CKD becomes prevalent in adults. Moreover, among SCD patients, exacerbation of anemia is an independent risk factor for acute kidney injury (AKI) which is a predisposing factor for CKD and End Stage Renal Diseases (ESRD), altogether contributing to 16–18% mortality among this patients’ population. The pathogenesis of renal diseases in SCD is not completely understood. While epidemiological studies have shown a strong association between rate of hemolysis, severity of anemia and CKD, intrinsic inflammatory, oxidative and hypercoagulative stress that contribute to the characteristic endothelial dysfunction also promotes development of renal diseases in SCD. This chapter will elaborately discuss current research on the pathogenesis of AKI, AKI-to-CKD transition and future research perspectives for development of novel therapeutic strategies

Optimizing Supply Decisions in a B2B Exchange Environment

The advent of the Internet is reshaping the landscape of B2B commerce in a significant manner. Emerging e-marketplaces are offering firms an opportunity to optimize their supply chain decisions across a variety of sourcing scenarios. In this paper, we have specifically focused on decision-making for systematic sourcing of make-to-order (MTO) items. We minimize sourcing and purchasing costs in the presence of fixed costs, shared capacity constraints, and volume-based discounts for bundles of items. We consider a private-exchange that facilitates collaborative sourcing and enables a buyer firm to aggregate demand across different units to gain savings from volume-based discounts on individual items or groups of items, avoiding the duplication of tooling investments, and reducing setup costs. Due to the computational complexity of this problem, we develop a heuristic procedure based on Lagrangian relaxation technique to solve the problem. The computational results show that the procedure is effective under a variety of scenarios

Identification of new genes in human chromosome 3 contig 7 by graphical representation technique

The rapidly growing library of genomic length sequences and the working draft of the human genome sequence imply a concomitant need to determine new methods to analyse the sequences for rapid identification of new genes and their functions. We have developed a graphical technique for quick determination of probable coding regions in DNA sequences. In this article we apply this technique to the new sequence data from human chromosome 3 contig 7 to test the efficacy of the proposed system in a live case, and also compare with results from other genomic sequences. We report here a sampling of sequence segments that pass theoretical tests of likelihood of being genes and list several that have close homology with sequences from the expressed sequence tag (EST) databases. We also comment on the possible use of the graphical representation technique in the shotgun method of gene sequencing

Optimal Control of Vertically Transmitted Disease: An Integrated Approach

We study the dynamics of a disease under administration of a vaccine and antiviral drug, where the disease transmits directly from the parents to the offspring (vertical transmission) and also through contact with infective individuals (horizontal transmission). While vaccination to those susceptible reduces the horizontal transmission, administration of the antiviral drug to infected individuals lessens the chance of vertical transmission. Thus the vaccine and antiviral drug play different roles in controlling the disease, which has both vertical and horizontal transmission. We develop a 3D model with Susceptible–Infected–Recovered under vaccination to the susceptible and antiviral treatment to the infected and consider a control theoretic approach using the Pontryagin maximum principle to analyse the costeffectiveness of the control process. Our results demonstrate that a mixed intervention strategy of vaccination and antiviral drug in a proper ratio is the most effective way to control the disease. We show that cost-effectiveness of both intervention strategies intimately depends on disease-related parameters, such as force of infection, probability of being infected to offspring from infected mothers, loss of immunity or reinfection and also on cost of treatment.</jats:p

Spatiotemporal Dysfunction of the Vascular Permeability Barrier in Transgenic Mice with Sickle Cell Disease

Sickle cell disease (SCD) is characterized by chronic intravascular hemolysis that generates excess cell-free hemoglobin in the blood circulation. Hemoglobin causes multiple endothelial dysfunctions including increased vascular permeability, impaired reactivity to vasoactive agonists, and increased adhesion of leukocytes to the endothelium. While the adhesive and vasomotor defects of SCD associated with cell-free hemoglobin are well defined, the vascular permeability phenotype remains poorly appreciated. We addressed this issue in two widely used and clinically relevant mouse models of SCD. We discovered that the endothelial barrier is normal in most organs in the young but deteriorates with aging particularly in the lung. Indeed, middle-aged sickle mice developed pulmonary edema revealing for the first time similarities in the chronic permeability phenotypes of the lung in mice and humans with SCD. Intravenous administration of lysed red blood cells into the circulation of sickle mice increased vascular permeability significantly in the lung without impacting permeability in other organs. Thus, increased vascular permeability is an endothelial dysfunction of SCD with the barrier in the lung likely the most vulnerable to acute inflammation

Essential role for ALCAM gene silencing in megakaryocytic differentiation of K562 cells

<p>Abstract</p> <p>Background</p> <p>Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells. However, its role in hematopoietic differentiation has not previously been defined.</p> <p>Results</p> <p>In this study, we show that ALCAM expression is silenced in erythromegakaryocytic progenitor cell lines. In agreement with this finding, the ALCAM promoter is occupied by GATA-1 <it>in vivo</it>, and a cognate motif at -850 inhibited promoter activity in K562 and MEG-01 cells. Gain-of-function studies showed that ALCAM clusters K562 cells in a process that requires PKC. Induction of megakaryocytic differentiation in K562 clones expressing ALCAM activated PKC-δ and triggered apoptosis.</p> <p>Conclusions</p> <p>There is a lineage-specific silencing of ALCAM in bi-potential erythromegakaryocytic progenitor cell lines. Marked apoptosis of ALCAM-expressing K562 clones treated with PMA suggests that aberrant ALCAM expression in erythromegakaryocytic progenitors may contribute to megakaryocytopenia.</p

Optimal Voting Rule and Minimization of Total Error Rate in Cooperative Spectrum Sensing for Cognitive Radio Networks, Journal of Telecommunications and Information Technology, 2021, nr 1

In cognitive radio technology, spectrum sensing is essential for detecting spectrum holes which may be allotted to secondary users. In this paper, an optimal voting rule is used for cooperative spectrum sensing while minimizing the total error rate (TER). The proposed spectrum sensing method is more energy-efficient and may be implemented in practice. It is relied upon in an improved energy detector whose utilization depends on the presence or absence of the primary user. Expressions for false alarm and missed detection probabilities are derived in the paper as well. Overall performance is analyzed both for AWGN and Rayleigh fading channels, in the presence of additive white Gaussian noise (AWGN). The optimum voting rule is applied to the cooperative spectrum sensing process in order to identify the optimum number of sensing nodes and the detection threshold. Finally, an energy-efficient spectrum sensing algorithm is proposed, requiring a lower number of cognitive users for a given error bound

Efficacy of nano-hydroxyapatite prepared by an aqueous solution combustion technique in healing bone defects of goat

The present study was undertaken to evaluate porous hydroxyapatite (HAp), the powder of which was prepared by a novel aqueous solution combustion technique, as a bone substitute in healing bone defects in vivo, as assessed by radiologic and histopathologic methods, oxytetracycline labeling, and angiogenic features in Bengal goat. Bone defects were created in the diaphysis of the radius and either not filled (group I) or filled with a HAp strut (group II). The radiologic study in group II showed the presence of unabsorbed implants which acted as a scaffold for new bone growth across the defect, and the quality of healing of the bone defect was almost indistinguishable from the control group, in which the defect was more or less similar, although the newly formed bony tissue was more organized when HAp was used. Histologic methods showed complete normal ossification with development of Haversian canals and well-defined osteoblasts at the periphery in group II, whereas the control group had moderate fibro-collagenization and an adequate amount of marrow material, fat cells, and blood vessels. An oxytetracycline labeling study showed moderate activity of new bone formation with crossing-over of new bone trabeculae along with the presence of resorption cavities in group II, whereas in the control group, the process of new bone formation was active from both ends and the defect site appeared as a homogenous non-fluoroscent area. Angiograms of the animals in the control group showed uniform angiogenesis in the defect site with establishment of trans-transplant angiogenesis, whereas in group II there was complete trans-transplant shunting of blood vessel communication. Porous HAp ceramic prepared by an aqueous combustion technique promoted bone formation over the defect, confirming their biologic osteoconductive property