Solving Large Scale Instances of the Distribution Design Problem Using Data Mining

In this paper we approach the solution of large instances of the distribution design problem. The traditional approaches do not consider that the instance size can significantly reduce the efficiency of the solution process. We propose a new approach that includes compression methods to transform the original instance into a new one using data mining techniques. The goal of the transformation is to condense the operation access pattern of the original instance to reduce the amount of resources needed to solve the original instance, without significantly reducing the quality of its solution. In order to validate the approach, we tested it proposing two instance compression methods on a new model of the replicated version of the distribution design problem that incorporates generalized database objects. The experimental results show that our approach permits to reduce the computational resources needed for solving large instances by at least 65%, without significantly reducing the quality of its solution. Given the encouraging results, at the moment we are working on the design and implementation of efficient instance compression methods using other data mining techniques

Vapor nanobubble is the more reliable photothermal mechanism for inducing endosomal escape of siRNA without disturbing cell homeostasis

Strategies for controlled delivery of therapeutic siRNA into living cells are in high demand as endosomal escape remains the most prominent bottleneck at the intracellular level. Photothermal properties of gold nanoparticles (AuNP) can be used to overcome the endosomal membrane barrier upon laser irradiation by two mechanisms: endosomal rupture by mechanical energy from water vapor nanobubbles (VNBs), or permeabilization of the endosomal membrane by heat diffusion. Here we evaluated how both mechanisms influence cargo release, transfection efficiency, acute cytotoxicity and cell homeostasis. Using a siRNA/AuNP drug delivery system we found that the in vitro release of siRNA from the AuNP carrier occurs equally efficiently by VNB formation or heat generation. Heat-mediated endosomal escape happened more efficiently in cells that had more particles per endosome, resulting in variable siRNA-induced downregulation (20-50%). VNB-mediated endosomal escape did not dependent on the number of AuNP per endosome, yielding high downregulations (50-60%) independent of the cell type. Effects on cell homeostasis by whole transcriptome analysis, showed a quick recover after 24 h or 48 h for either of both photothermal mechanisms. We conclude that VNBs are more consistent to induce efficient endosomal escape and gene silencing independent of the cell type without long lasting effects on cell homeostasis

Lessons from Mycobacterium avium complex-associated pneumonitis: a case report

ABSTRACT: INTRODUCTION: Mycobacterium avium complex (MAC) is an increasingly recognized cause of pulmonary disease in immunocompetent individuals. An acute form of MAC lung disease, MAC-associated pneumonitis, has generally been associated with the use of hot tubs. There is controversy in the literature about whether MAC-associated pneumonitis is a classic hypersensitivity pneumonitis or is a direct manifestation of mycobacterial infection. CASE PRESENTATION: We report the second case in the literature of MAC-associated pneumonitis not related to the use of hot tubs. The source of MAC in a 52-year-old immunocompetent patient was an intrapulmonary cyst containing numerous acid-fast bacilli. The patient developed disseminated miliary nodules throughout both lung fields. Histological examination of resected lung tissue revealed well-formed, acid-fast negative granulomas composed predominantly of CD4+ T-cells and CD68+ histiocytes. The granulomas were strongly positive for tumor necrosis factor-alpha, a pro-inflammatory cytokine. CONCLUSION: The attempt to classify MAC-associated pneumonitis as either a classic hypersensitivity pneumonitis or a direct manifestation of mycobacterial infection is not particularly useful. Our case demonstrates that MAC-associated pneumonitis is characterized by a vigorous T-helper 1-like, pro-inflammatory, immune response to pulmonary mycobacterial infection. The immunopathology provides a rationale for clinical studies of anti-MAC therapy with the addition of anti-inflammatory agents (for example, corticosteroids) to hasten the resolution of infection and symptoms

Preneoplastic lesions of the lung

Lung cancer is the leading cause of cancer deaths worldwide. If we can define and detect preneoplastic lesions, we might have a chance of improving survival. The World Health Organization has defined three preneoplastic lesions of the bronchial epithelium: squamous dysplasia/carcinoma in situ; atypical adenomatous hyperplasia; and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. These lesions are believed to progress to squamous cell carcinoma, adenocarcinoma and carcinoid tumors, respectively. In this review we summarize the data supporting the preneoplastic nature of these lesions, and delve into some of the genetic changes found in atypical adenomatous hyperplasia and squamous dysplasia/carcinoma in situ

Herpes simplex virus bronchiolitis in a cannabis user

Herpes simplex virus (HSV) lower respiratory tract infections in adults are uncommon. We present a case of HSV bronchiolitis and pneumonitis in an immunocompetent individual, likely linked to chronic habitual marijuana use and a herpetic orolabial ulcer. The case serves as a reminder to consider HSV as a potential unusual cause of lower respiratory tract infection/inflammation in individuals with chronic habitual marijuana use

Co-Occurring Conduct Problems and Anxiety: Implications for the Functioning and Treatment of Youth with Oppositional Defiant Disorder

Conduct problems and anxiety symptoms commonly co-occur among youths with oppositional defiant disorder (ODD); however, how these symptoms influence functioning and treatment outcomes remains unclear. This study examined subtypes based on these co-occurring symptoms in a clinical sample of 134 youths (Mage = 9.67, 36.6% female, 83.6% white) with ODD and the predictive power of these subgroups for youth functioning and psychosocial treatment outcomes. The latent profile analysis (LPA) was used to identify subgroups based on parent- and self-reported conduct problems and anxiety symptoms. Differences among the subgroups in clinician-, parent-, and/or self-reported accounts of symptom severity, school performance, underlying processing known to be impaired across ODD, conduct and anxiety disorders, self-concept, and psychosocial treatment outcomes were examined. Four distinct profiles were identified: (1) Low Anxiety/Moderate Conduct Problems (n = 42); (2) High Anxiety/Moderate Conduct Problems (n = 33); (3) Moderate Anxiety/Moderate Conduct Problems (n = 40); and (4) Moderate Anxiety/High Conduct Problems (n = 19). The Moderate Anxiety/High Conduct Problems group exhibited more severe behavioral problems, greater difficulties with negative emotionality, emotional self-control, and executive functioning; they also demonstrated worse long-term treatment outcomes than the other subgroups. These findings suggest more homogeneous subgroups within and across diagnostic categories may result in a deeper understanding of ODD and could inform nosological systems and intervention efforts

Lessons from <it>Mycobacterium avium</it> complex-associated pneumonitis: a case report

Abstract Introduction Mycobacterium avium complex (MAC) is an increasingly recognized cause of pulmonary disease in immunocompetent individuals. An acute form of MAC lung disease, MAC-associated pneumonitis, has generally been associated with the use of hot tubs. There is controversy in the literature about whether MAC-associated pneumonitis is a classic hypersensitivity pneumonitis or is a direct manifestation of mycobacterial infection. Case presentation We report the second case in the literature of MAC-associated pneumonitis not related to the use of hot tubs. The source of MAC in a 52-year-old immunocompetent patient was an intrapulmonary cyst containing numerous acid-fast bacilli. The patient developed disseminated miliary nodules throughout both lung fields. Histological examination of resected lung tissue revealed well-formed, acid-fast negative granulomas composed predominantly of CD4+ T-cells and CD68+ histiocytes. The granulomas were strongly positive for tumor necrosis factor-α, a pro-inflammatory cytokine. Conclusion The attempt to classify MAC-associated pneumonitis as either a classic hypersensitivity pneumonitis or a direct manifestation of mycobacterial infection is not particularly useful. Our case demonstrates that MAC-associated pneumonitis is characterized by a vigorous T-helper 1-like, pro-inflammatory, immune response to pulmonary mycobacterial infection. The immunopathology provides a rationale for clinical studies of anti-MAC therapy with the addition of anti-inflammatory agents (for example, corticosteroids) to hasten the resolution of infection and symptoms.</p

Algorithms solving the Internet shopping optimization problem with price discounts

The Internet shopping optimization problem arises when a customer aims to purchase a list of goods from a set of web-stores with a minimum total cost. This problem is NP-hard in the strong sense. We are interested in solving the Internet shopping optimization problem with additional delivery costs associated to the web-stores where the goods are bought. It is of interest to extend the model including price discounts of goods. The aim of this paper is to present a set of optimization algorithms to solve the problem. Our purpose is to find a compromise solution between computational time and results close to the optimum value. The performance of the set of algorithms is evaluated through simulations using real world data collected from 32 web-stores. The quality of the results provided by the set of algorithms is compared to the optimal solutions for small-size instances of the problem. The optimization algorithms are also evaluated regarding scalability when the size of the instances increases. The set of results revealed that the algorithms are able to compute good quality solutions close to the optimum in a reasonable time with very good scalability demonstrating their practicability