Pricing in column generation for a robust airline crew pairing problem

The crew pairing problem is to find the least costly set of pairings so that each flight given in the flight schedule is covered. In this study, the robust crew pairing problem is considered. That is, the selected pairings cover the regular flights and also provide solutions to cover some extra flights which may be introduced into the flight schedule during the operation at a later point in time. The crew pairing problem is usually solved by column generation in which the pricing subproblem becomes a multi-label shortest path problem. For the robust crew pairing problem the multi-label shortest path problem requires some modifications to solve two column generation approaches proposed by Çoban [10]. These modifications of the pricing problem with associated labels and the domination rules are presented. The complexity of the multi-label shortest path problem grows exponentially as the number of flights (nodes) in the flight schedule increases. This curse of dimensionality is solved by using approximate and exact pruning rules. Also, a buffer column pool is formed as an intermediate step in order to find a negative reduced cost pairing without solving the multi-label shortest path problem at every iteration of the column generation algorithm. In the multi-label shortest path problem, the approximate rules based on the score-calculation are used for early pruning of the paths on the processed nodes. The optimal solution may be missed because of the coarse structure of the approximate rules. When a pairing that improves the objective function cannot be found by applying the approximate rules, we switch to the exact pruning. Another method is using a hybrid approach that applies both approximate and exact rules in the same iteration to find the optimal solution. The performance of our solution approach is demonstrated through a computational study by using actual data from a local airline

Investigation of the effects of mir-219-1 gene variants on the development of disease in non-small cell lung cancer patients

Background: Various variants of the miR-219-1 gene are one of the first genes associated with NSCLC prognosis in the literature. Objectives: We aimed to genotype two different variants of the miR-219-1 gene and to investigate to using of the result as a biomarker in the diagnosis and treatment of NSCLC. Materials and Methods: The patients were chosen according to International NSCLC criteria and genomic DNA was isolated from blood (138 patients and 100 healthy individuals). Then qRT-PCR was applied to determine the rs213210 and rs421446 variants of miR-219-1 gene polymorphisms. Allele and genotype frequencies were compared using Pearson’s chi-square and Fisher’s exact tests test. Results: We found that TT genotype (p=0,381) in rs213210 compared with CC genotype (p=0,165) and CC genotype (p=0,823) in rs421446 compared with TT genotype (p=0,537) did not show a significantly increased risk of NSCLC. There is no relationship between polymorphisms in miR-219-1 and the outcome of NSCLC. Conclusion: miRNA single nucleotide polymorphisms can be used as genetic biomarkers to predict cancer susceptibility, early diagnosis, and prognosis. Our study has shown that two variants of miR-219-1 were not related to NSCLC in the Turkish population. The reason for this can be differences in ethnicity, regions, and background of population and these differences could lead to various outcomes. Keywords: NSCLC; miR-219-1 gene; single-nucleotide polymorphisms

Immune Response and Therapeutic Vaccination against Helicobacter pylori

Abstract Helicobacter pylori (H. pylori) is a gram-negative bacterium, considered one of the significant discoveries about 40 years ago, and was isolated and cultured from the human stomach. H. pylori has infected more than half of the human population, making it one of the most well-known human pathogens. The front line of immune response starts with innate recognition of H. pylori and its mediators and intracellular signaling by gastric epithelial cells in which they recognize and respond to bacterial products such as flagella, lipopolysaccharides, and peptidoglycan. The inflammatory response is followed by the recruitment of various cells of the innate and adaptive immune system. Cytokines including IL-12, IL-23, and TGF-β direct the polarization of CD4+ T helper cells to Th1, Th17, and Treg, respectively. The clinical symptoms that may occur as a result of H. pylori infection linked to the virulence factors of the bacteria, the genetic factors of the host, and the immune responses. Specific antigens have been found as part of these crucial virulence factors. The specific antigens may play a role in the development of an effective vaccine to eradicate H. pylori infection. Innate and adaptive immunity and genetic factors have an important place in understanding the host response mechanisms, elucidating the pathogenesis of the disease, and developing new targeted therapy approaches. Thus, the aim of this study is to understand immune responses and investigate the potential therapeutic vaccination against H. pylori

A vehicle routing problem with flexible time windows

In this paper, we introduce the Vehicle Routing Problem with Flexible Time Windows (VRPFlexTW), in which vehicles are allowed to deviate from customer time windows by a given tolerance. This flexibility enables savings in the operational costs of carriers, since customers may be served before and after the earliest and latest time window bounds, respectively. However, as time window deviations are undesired from a customer service perspective, a penalty proportional to these deviations is accounted for in the objective function. We develop a solution procedure, in which feasible vehicle routes are constructed via a tabu search algorithm. Furthermore, we propose a linear programming model to handle the detailed scheduling of customer visits for given routes. We validate our solution procedure by a number of Vehicle Routing Problem with Time Windows (VRPTW) benchmark instances. We highlight the costs involved in integrating flexibility in time windows and underline the advantages of the VRPFlexTW, when compared to the VRPTW

Chemotherapy with pegylated liposomal doxorubicin and cisplatin in recurrent platinum-sensitive epithelial ovarian cancer

Background. Pegylated liposomal doxorubicin (PLD) is the only nonplatinum agent to significantly improve survival in patients with platinum-sensitive recurrent ovarian cancer. The present study was designed to assess the efficacy and safety of PLD plus cisplatin combination therapy in these patients

A pilot study evaluating the efficacy and toxicity of biweekly gemcitabine and pegylated liposomal doxorubicin in recurrent platinum-resistant epithelial ovarian cancer

Background. Both gemcitabine and pegylated liposomal doxorubicin (PLD) are antineoplastic drugs with clinical activity in patients with platinum-resistant ovarian cancer. The present study was designed to assess the efficacy and safety of biweekly scheduled gemcitabine and PLD combination therapy in such patients

Addition of topotecan to standard cisplatin/etoposide combination in patients with extended stage small cell lung carcinoma

Background: Topotecan is an active agent for the management of untreated and recurrent extensive-disease small cell tung cancer, (ED-SCLC). This study was designed to evaluate the efficacy and safety of a triplet combination with topotecan added to the standard PE regimen in previously untreated patients with ED-SCLC

Biweekly administration of gemcitabine and cisplatin chemotherapy in patients with anthracycline and taxane-pretreated metastatic breast cancer

Gemcitabine and cisplatin are the active agents in metastatic breast cancer pretreated with anthracycline and/or taxane as a second line treatment. The present study was designed to assess the efficacy and safety of this regimen given biweekly schedule in these patients. Twenty-seven women, median age 57, with metastatic breast cancer previously treated with anthracycline and taxane were eligible for enrollment. Gemcitabine was administered intravenously on days 1 and 15 at a dose of 2,000 mg/m(2) and Cisplatin was given intravenously on day 1 and 15 at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. Of all 27 evaluable patients, the overall response rate was 26% (7 of 27; 95% CI: 11-46%) with seven all partial responses. The stable diseases were found in 9 (33%) patients. At the time of last follow-up, 11 (41%) of the patients died of their disease progression. The median overall survival duration was 7.4 +/- 2.8 months. The 1-year overall survival rate was 46.9% +/- 12.3. Hematological toxicity was not found as the principal dose-limiting toxicity. Severe (grade III/IV) neutropenia was observed only one (4%) patients. No patient was complicated by febrile neutropenia and G-CSF usage was not performed. Grade III and IV anemia were seen in only 4 (15%) and thrombocytopenia was noted only one (4%) patients. Severe hepatic (n=2) and renal toxicity (n=1) were observed and these all recovered completely without complication. Several other severe non-hematological side effects were managed easily

Social approach and avoidance behaviour for negative emotions is modulated by endogenous oxytocin and paranoia in schizophrenia

Patients with schizophrenia suffer from dysfunctional social behaviour. Social approach and avoidance (AA) has been associated with motor responses,as the affective valence and gaze direction of facial stimuli can bias push and pull motor tendencies. The aim of this study was to investigate the role of endogenous oxytocin in social AA behaviour in schizophrenia. Basal plasma oxytocin levels were collected from 28 patients who were then given a joystick-based Approach Avoidance Task(AAT). Reaction times were recorded and AAT effect scores calculated for responses to happy and angry faces, which either had direct or averted gaze. Individual differences in basal oxytocin had a significant relationship with AAT responses, and patients with higher levels of oxytocin tended to avoid angry faces more. Furthermore, greater avoidance of angry faces was correlated with more severepsychotic (positive and general) symptoms and greater paranoia. This suggests that the endogenous effects of oxytocin may be specific to the interpretation of negative threatening emotions in schizophrenia patients and also provides evidence that psychotic symptoms and paranoia can impact on social AA behaviour by heightening threat avoidance