Integrated Inventory Control and Facility Location Decisions in a Multi-Echelon Supply Chain Network with Hubs

This paper develops mathematical models to coordinate facility location and inventory control for a four-echelon supply chain network consisting of multiple suppliers, warehouses, hubs and retailers. The hubs help in reducing transportation costs by consolidating products from multiple warehouses and directing the larger shipments to the retailer. The integrated models studied in this paper simultaneously determines three types of decisions: (i) facility location—the number and location of warehouses and hubs, (ii) allocation—assignment of suppliers to located warehouses and retailers to located warehouses via the location hubs, and (iii) inventory control decisions at each located warehouse. The goal is to minimize the facility location, transportation and the inventory costs. A mixed integer nonlinear programming formulation is first presented. The nonlinear integer programming formulation is then transformed into a conic mixed integer program and a novel and compact conic mixed integer programming formulation. Computational runs are conducted using commercial solvers to compare the performance of the different formulations. The compact conic mixed integer programming formulation was found to significantly outperform the other formulations by achieving significant computational savings. The results demonstrate that large scale instances of certain multi-echelon supply chain network design problems can be solved using commercial solvers through intelligent reformulation of the model.     

Finding structure in noisy text: topic classification and unsupervised clustering

This paper addresses two types of classification of noisy, unstructured text such as newsgroup messages: (1) spotting messages containing topics of interest, and (2) automatic conceptual organization of messages without prior knowledge of topics of interest. In addition to applying our hidden Markov model methodology to spotting topics of interest in newsgroup messages, we present a robust methodology for rejecting messages which are off-topic. We describe a novel approach for automatically organizing a large, unstructured collection of messages. The approach applies an unsupervised topic clustering procedure to generate a hierarchical tree of topics.     

Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma

The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including NRAS, HRAS, and, most importantly, KRAS. A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the KRAS gene. Due to this fact, studying the function of KRAS and the impact of its mutations on the tumor microenvironment (TME) is a priority for understanding pancreatic cancer progression and designing novel therapeutic strategies for the treatment of the dismal disease. Despite some recent enlightening studies, there is still a wide gap in our knowledge regarding the impact of KRAS mutations on different components of the pancreatic TME. In this review, we will present an updated summary of mutant KRAS role in the initiation, progression, and modulation of the TME of pancreatic ductal adenocarcinoma (PDAC). This review will highlight the intriguing link between diabetes mellitus and PDAC, as well as vitamin D as an adjuvant effective therapy via TME modulation of PDAC. We will also discuss different ongoing clinical trials that use KRAS oncogene signaling network as therapeutic targets.     

Mechanobiology of platelets: techniques to study the role of fluid flow and platelet retraction forces at the micro- and nano-scale

Coagulation involves a complex set of events that are important in maintaining hemostasis. Biochemical interactions are classically known to regulate the hemostatic process, but recent evidence has revealed that mechanical interactions between platelets and their surroundings can also play a substantial role. Investigations into platelet mechanobiology have been challenging however, due to the small dimensions of platelets and their glycoprotein receptors. Platelet researchers have recently turned to microfabricated devices to control these physical, nanometer-scale interactions with a higher degree of precision. These approaches have enabled exciting, new insights into the molecular and biomechanical factors that affect platelets in clot formation. In this review, we highlight the new tools used to understand platelet mechanobiology and the roles of adhesion, shear flow, and retraction forces in clot formation.     

New approach to bone tissue engineering: simultaneous application of hydroxyapatite and bioactive glass coated on a poly(L-lactic acid) scaffold

A combination of bioceramics and polymeric nanofibers holds promising potential for bone tissue engineering applications. In the present study, hydroxyapatite (HA), bioactive glass (BG), and tricalcium phosphate (TCP) particles were coated on the surface of electrospun poly(L-lactic acid) (PLLA) nanofibers, and the capacity of the PLLA, BG-PLLA, HA-PLLA, HA-BG-PLLA, and TCP-PLLA scaffolds for bone regeneration was investigated in rat critical-size defects using digital mammography, multislice spiral-computed tomography (MSCT) imaging, and histological analysis. Electrospun scaffolds exhibited a nanofibrous structure with a homogeneous distribution of bioceramics along the surface of PLLA nanofibers. A total of 8 weeks after implantation, no sign of complication or inflammation was observed at the site of the calvarial bone defect. On the basis of imaging analysis, a higher level of bone reconstruction was observed in the animals receiving HA-, BG-, and TCP-coated scaffolds compared to an untreated control group. In addition, simultaneous coating of HA and BG induced the highest regeneration among all groups. Histological staining confirmed these findings and also showed an efficient osseointegration in HA-BG-coated nanofibers. On the whole, it was demonstrated that nanofibrous structures could serve as an appropriate support to guide the healing process, and coating their surface with bioceramics enhanced bone reconstruction. These bioceramic-coated scaffolds can be used as new bone-graft substitutes capable of efficiently inducing osteoconduction and osseointegration in orthopedic fractures and defects.     

A new combined method based on curvelet transform and morphological operators for automatic detection of foveal avascular zone

In order to achieve early detection of diabetic retinopathy (DR) for the sake of preventing from blindness, regular screening using retinal photography is necessary. Abnormalities of DR do not have uniform distribution over the retina. Certain types of abnormalities usually occur in specific areas on the retina. The distance between lesions, such as micro-aneurysms, and the foveal avascular zone (FAZ) is a useful feature for later analysis and grading of DR. In this paper, a new fully automatic system is presented to find the location of FAZ in fundus fluorescein angiogram photographs. The method is based on two procedures: digital curvelet transform (DCUT) and morphological operations. Firstly, end points of vessels are detected based on vessel segmentation using DCUT. By connecting these points in the selected region of interest, FAZ region is extracted. Secondly, vessels are subtracted from the retinal image, and morphological dilatation and erosion are applied on the resulted image. By choosing an appropriate threshold, FAZ region is detected. The final FAZ region is extracted by performing logical AND between two segmented FAZ. Our experiments show that the system achieves, respectively, the specificity and sensitivity of (>98 and >96 %) for normal stage, for mild/moderate non-proliferative DR (NPDR) (>98, and >95 %) and for Sever NPDR + PDR (>97 and >93 %).     

Pro-labour myometrial gene expression: are preterm labour and term labour the same?

Preterm labour (PTL) is the most important cause of neonatal morbidity and mortality. While some causes have been identified, the mechanisms involved remain elusive. This study investigates whether term labour (TL) is an appropriate model for PTL by examining pro-labour gene expression, using quantitative rtPCR, and protein synthesis, using Western analysis, in preterm and term myometrial samples obtained from the upper and lower uterine segments before and after the onset of labour. In the lower segment, the levels of prostaglandin H synthase type-2 (PGHS-2), interleukin-1beta (IL-1beta), IL-6 and IL-8 mRNA expression were significantly higher in TL compared with PTL samples. Compared with non-labour controls, the expression of IL-1beta and IL-8 mRNA was increased in both PTL and TL samples and the expression of PGHS-2 and IL-6 mRNA was increased in TL samples only. In the upper segment, there were no differences between PTL and TL samples and the mRNA expression of PGHS-2 and IL-1beta was increased in TL compared with term no labour samples. No effect of PTL or TL was seen on either oxytocin receptor or connexin-43 mRNA expression or protein levels. The multiple regression analysis and studies in primary cultures of uterine myocytes suggest that the inflammatory cytokines, IL-1beta and tumour necrosis factor-alpha, are the most important regulators of PGHS-2 and IL-8. Our data show that preterm and term labouring myometrium are significantly different and that the most marked labour-induced changes in gene expression are in the lower segment. These changes may occur in response to the release of inflammatory cytokines by the labour-associated inflammatory infiltration.