GRASP algorithms for the robust railway network design problem

This paper analyzes the solvability of a railway network design problem and its robust version. These problems are modeled as integer linear programming problems with binary variables, and their solutions provide topological railway networks maximizing the trip coverage in the presence of a competing mode, both assuming that the network works fine and that links can fail, respectively. Since these problems are computationally intractable for realistic sizes, GRASP heuristics are proposed for finding good feasible solutions. The results obtained in a computational experience indicate that our GRASP algorithms are suitable for railway network design problems. © 2011 Springer Science+Business Media, LLC.We would like to thank the Spanish Ministerio de Fomento under grant PT-2007-003, Ministerio de Ciencia y Educacion under grant MTM2009-14243, the Junta de Andalucia under grant P09-TEP-5022 for supporting this research, the FEDER funds of the European Union and TUSSAM (Seville, Spain). Special thanks are due to two anonymous referees for their valuable comments.García-Archilla, B.; Lozano, AJ.; Mesa, JA.; Perea Rojas Marcos, F. (2011). GRASP algorithms for the robust railway network design problem. Journal of Heuristics. 19(2):399-422. https://doi.org/10.1007/s10732-011-9185-zS399422192Baaj, M., Mahmassani, H.: An AI-based approach for transit route system planning and design. J. Adv. Transp. 25(2), 187–210 (1991)Cancela, H., Robledo, F., Rubino, G.: A grasp algorithm with tree based local search for designing a survivable wide area network backbone. J. Comput. Sci. Technol. 4(1), 52–58 (2004)Díaz, J.A., Luna, D., Luna, R.: A grasp heuristic for the manufacturing cell formation problem. TOP (2011). doi: 10.1007/s11750-010-0159-3Feo, T., Resende, M.: A probabilistic heuristic for a computationally difficult set covering problem. Oper. Res. Lett. 8, 67–71 (1989)Goossens, J., van Hoesel, C., Kroon, L.: A branch-and-cut approach for solving railway line-planning problems. Transp. Sci. 38, 379–393 (2004)Institute of Electrical and Electronics Engineers: IEEE Standard Computer Dictionary: A Compilation of IEEE Standard Computer Glossaries (1990)Laporte, G., Mesa, J., Perea, F.: A game theoretic framework for the robust railway transit network design problem. Transp. Res., Part B, Methodol. 44, 447–459 (2010)Laporte, G., Marín, A., Mesa, J., Perea, F.: Designing robust rapid transit networks with alternative routes. J. Adv. Transp. 45, 54–65 (2011)Marín, A., García-Ródenas, R.: Location of infrastructure in urban railway networks. Comput. Oper. Res. 36, 1461–1477 (2009)Marín, A., Jaramillo, P.: Urban rapid transit network design: accelerated Benders decomposition. Ann. Oper. Res. 169(1), 35–53 (2009)Marín, A., Mesa, J.A., Perea, F.: Integrating robust railway network design and line planning under failures. Lect. Notes Comput. Sci. 5868, 273–292 (2009)Mauttone, A., Urquhart, M.E.: A route set construction algorithm for the transit network design problem. Comput. Oper. Res. 36, 2440–2449 (2009)Murphey, R., Pardalos, P., Pitsoulis, L.: A GRASP for the multitarget multisensor tracking problem. In: Networks. Discrete Mathematics and Theoretical Computer Science Series, vol. 40, pp. 277–302. American Mathematical Society, Providence (1998)Nesmachnow, S., Cancela, H., Alba, E.: Evolutionary algorithms applied to reliable communication network design. Eng. Optim. 39(7), 831–855 (2007)Schöbel, A., Scholl, S.: Line planning with minimal transfers. In: 5th Workshop on Algorithmic Methods and Models for Optimization of Railways, Number 06901 in Dagstuhl Seminar Proceedings (2006

BLV: Lessons on vaccine development

Vaccination against retroviruses is a challenge because of their ability to stably integrate into the host genome, undergo long-term latency in a proportion of infected cells and thereby escape immune response. Since clearance of the virus is almost impossible once infection is established, the primary goal is to achieve sterilizing immunity. Besides efficacy, safety is the major issue since vaccination has been associated with increased infection or reversion to pathogenicity. In this review, we discuss the different issues that we faced during the development of an efficient vaccine against bovine leukemia virus (BLV). We summarize the historical failures of inactivated vaccines, the efficacy and safety of a live-attenuated vaccine and the economical constraints of further industrial development.Fil: Abdala, Alejandro Ariel. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Brossel, Hélène. Université de Liège; BélgicaFil: Calvinho, Luis Fernando. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Carignano, Hugo Adrián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Franco, Lautaro Nahuel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Gazon, Hélène. Université de Liège; BélgicaFil: Gillissen, Christelle. Université de Liège; BélgicaFil: Hamaidia, Malik. Université de Liège; BélgicaFil: Hoyos, Clotilde. Université de Liège; BélgicaFil: Jacques, Jean Rock. Université de Liège; BélgicaFil: Joris, Thomas. Université de Liège; BélgicaFil: Laval, Florent. Université de Liège; BélgicaFil: Petersen Cruceño, Marcos Iván. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Porquet, Florent. Université de Liège; BélgicaFil: Porta, Natalia Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Ruiz, Vanesa. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Safari, Roghaiyeh. Université de Liège; BélgicaFil: Suárez Archilla, Guillermo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Willems, Luc. Université de Liège; Bélgic

A safe and effective vaccine against bovine leukemia virus

peer reviewedPrevious attempts to develop a vaccine against bovine leukemia virus (BLV) have not been successful because of inadequate or short-lived stimulation of all immunity components. In this study, we designed an approach based on an attenuated BLV provirus by deleting genes dispensable for infectivity but required for efficient replication. The ability of the vaccine to protect from natural BLV infection was investigated in the context of dairy productive conditions in an endemic region. The attenuated vaccine was tested in a farm in which the prevalence rose from 16.7% in young cattle at the beginning of the study to more than 90% in adult individuals. Sterilizing immunity was obtained in 28 out of 29 vaccinated heifers over a period of 48 months, demonstrating the effectiveness of the vaccine. As indicated by the antiviral antibody titers, the humoral response was slightly reduced compared to wild-type infection. After initial post-vaccination bursts, the proviral loads of the attenuated vaccine remained most frequently undetectable. During the first dairy cycle, proviral DNA was not detected by nested-PCR in milk samples from vaccinated cows. During the second dairy cycle, provirus was sporadically detected in milk of two vaccinated cows. Forty-two calves born from vaccinated cows were negative for proviral DNA but had antiviral antibodies in their peripheral blood. The attenuated strain was not transmitted to sentinels, further supporting the safety of the vaccine. Altogether, these data thus demonstrate that the vaccine against BLV is safe and effective in herd conditions characterized by a very high incidence. This cost-effective approach will thus decrease the prevalence of BLV without modification of production practices. After facing a series of challenges pertaining to effectiveness and biosafety, the vaccine is now available for further large-scale delivery. The different challenges and hurdles that were bypassed may be informative for the development of a vaccine against HTLV-1

Post-mortem neuropathologic examination of a 5-case series of CAR T-cell treated patients

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for the treatment of refractory hematopoietic malignancies. Adverse events are common, and neurotoxicity is one of the most important. However, the physiopathology is unknown and neuropathologic information is scarce.Materials and methods: Post-mortem examination of 6 brains from patients that underwent CAR T-cell therapy from 2017 to 2022. In all cases, polymerase chain reaction (PCR) in paraffin blocks for the detection of CAR T cells was performed.Results: Two patients died of hematologic progression, while the others died of cytokine release syndrome, lung infection, encephalomyelitis, and acute liver failure. Two out of 6 presented neurological symptoms, one with extracranial malignancy progression and the other with encephalomyelitis. The neuropathology of the latter showed severe perivascular and interstitial lymphocytic infiltration, predominantly CD8+, together with a diffuse interstitial histiocytic infiltration, affecting mainly the spinal cord, midbrain, and hippocampus, and a diffuse gliosis of basal ganglia, hippocampus, and brainstem. Microbiological studies were negative for neurotropic viruses, and PCR failed to detect CAR T -cells. Another case without detectable neurological signs showed cortical and subcortical gliosis due to acute hypoxic-ischemic damage. The remaining 4 cases only showed a mild patchy gliosis and microglial activation, and CAR T cells were detected by PCR only in one of them.Conclusions: In this series of patients that died after CAR T-cell therapy, we predominantly found non-specific or minimal neuropathological changes. CAR T-cell related toxicity may not be the only cause of neurological symptoms, and the autopsy could detect additional pathological findings

Expression-based analysis of genes related to single nucleotide polymorphism hits associated with bovine leukemia virus proviral load in Argentinean dairy cattle

In dairy cattle infected with bovine leukemia virus (BLV), the proviral load (PVL) level is directly related to the viral transmission from infected animals to their healthy herdmates. Two contrasting phenotypic groups can be identified when assessing PVL in peripheral blood of infected cows. A large number of reports point to bovine genetic variants (single nucleotide polymorphisms) as one of the key determinants underlying PVL level. However, biological mechanisms driving BLV PVL profiles and infection progression in cattle have not yet been elucidated. In this study, we evaluated whether a set of candidate genes affecting BLV PVL level according to whole genome association studies are differentially expressed in peripheral blood mononuclear cells derived from phenotypically contrasting groups of BLV-infected cows. During a 10-mo-long sampling scheme, 129 Holstein cows were phenotyped measuring anti-BLV antibody levels, PVL quantification, and white blood cell subpopulation counts. Finally, the expression of 8 genes (BOLA-DRB3, PRRC2A, ABT1, TNF, BAG6, BOLA-A, LY6G5B, and IER3) located within the bovine major histocompatibility complex region harboring whole genome association SNP hits was evaluated in 2 phenotypic groups: high PVL (n = 7) and low PVL (n = 8). The log2 initial fluorescence value (N0) transformed mean expression values for the ABT1 transcription factor were statistically different in high- and low-PVL groups, showing a higher expression of the ABT1 gene in low-PVL cows. The PRRC2A and IER3 genes had a significant positive (correlation coefficient = 0.61) and negative (correlation coefficient = −0.45) correlation with the lymphocyte counts, respectively. Additionally, the relationships between gene expression values and lymphocyte counts were modeled using linear regressions. Lymphocyte levels in infected cows were better explained (coefficient of determination = 0.56) when fitted a multiple linear regression model using both PRRC2A and IER3 expression values as independent variables. The present study showed evidence of differential gene expression between contrasting BLV infection phenotypes. These genes have not been previously related to BLV pathobiology. This valuable information represents a step forward in understanding the BLV biology and the immune response of naturally infected cows under a commercial milk production system. Efforts to elucidate biological mechanisms leading to BLV infection progression in cows are valuable for BLV control programs. Further studies integrating genotypic data, global transcriptome analysis, and BLV progression phenotypes are needed to better understand the BLV–host interaction.Instituto de VirologíaFil: Petersen, Marcos Iván. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Petersen, Marcos Iván. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Petersen, Marcos Iván. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Carignano, Hugo Adrian. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Suarez Archilla, Guillermo. INTA. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Caffaro, María Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Alvarez, Irene. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Miretti, Marcos Mateo. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Instituto de Biología Subtropical. Grupo de Investigación en Genética Aplicada; ArgentinaFil: Miretti, Marcos Mateo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Trono, Karina Gabriela. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentin

Prejuicio y distancia social hacia las personas gays y lesbianas en una muestra de empleados en Puerto Rico: estudio exploratorio

Through a quantitative, exploratory-descriptive and non-experimental study, the prejudiced attitude (PA) and social distancing (SD) towards lesbian and gay people were examined in a sample of workers in Puerto Rico. The sample consisted of 779 participants, in which, 61 %were women between the age range of 21 to 40 years. The results indicated that workers exhibited low levels of PA (M=85.47) and low levels of SD (M=18.14) towards (LG) people. Moreover, we found a direct, moderately high and significant relationship between these variables, r (777) = .63, p<.01. When considering sexual orientation, heterosexuals expressed higher PA and SD towards LG people than non-heterosexuals. In respect to political perspective, conservatives showed more PA and SD than liberals. Finally, when considering religious practices, those who reported attending to some religious services weekly indicated higher PA and SD than those who reported never attending. In conclusion, although the PA and SD in workers towards LG people are expressed in low levels, they continue to be present. A relatively high proportion of non-heterosexuals participating in the study (29 %) may have had an impact on the low levels of PA and SD found. This study provides relevant information about the attitudes of workers in relation to sexual minorities, which allows organizations to develop diversity programs that are more inclusive and LGBT-friendlyMediante un estudio cuantitativo, exploratorio-descriptivo y no experimental, se examinó la actitud prejuiciada (AP) y el distanciamiento social (DS) hacia las personas lesbianas y gays (LG) en una muestra de trabajadores en Puerto Rico. La muestra estuvo compuesta por 779 participantes, de los cuales 61 % fueron mujeres entre el rango de edad de 21 a 40 años. Los resultados reflejaron que los trabajadores muestran niveles bajos de AP (M=85.47) y niveles bajos de DS (M=18.14) hacia las personas LG. Igualmente, encontramos una relación directa, moderadamente alta y significativa entre dichas variables, r (777) = .63, p<.01. Al considerar la orientación sexual, los heterosexuales manifestar on mayor AP y DS hacia las personas LG que los no-heterosexuales. Respecto a la perspectiva política, los conservadores manifestaron más AP y DS que los liberales. Por último, al considerar las prácticas religiosas, los que asisten semanalmente a algún servicio religioso mostraron mayor AP y DS que los que nunca van. En conclusión, aunque las AP y la DS de los trabajadores hacia las personas LG se manifiestan en niveles bajos, aún siguen presentes. Una participación relativamente alta de personas no-heterosexuales (29 %) pudo haber incidido en los niveles bajos de AP y DS hallados. Este estudio provee información relevante sobre las actitudes de los trabajadores en relación a las minorías sexuales, lo que permite a las organizaciones desarrollar programas dediversidad más inclusivos y LGBT-amigable

Prejuicio y distancia social hacia las personas gays y lesbianas en una muestra de empleados en Puerto Rico: estudio exploratorio

Through a quantitative, exploratory-descriptive and non-experimental study, the prejudiced attitude (PA) and social distancing (SD) towards lesbian and gay people were examined in a sample of workers in Puerto Rico. The sample consisted of 779 participants, in which, 61 % were women between the age range of 21 to 40 years. The results indicated that workers exhibited low levels of PA (M=85.47) and low levels of SD (M=18.14) towards (LG) people. Moreover, we found a direct, moderately high and significant relationship between these variables, r (777) = .63, p&lt;.01. When considering sexual orientation, heterosexuals expressed higher PA and SD towards LG people than non-heterosexuals. In respect to political perspective, conservatives showed more PA and SD than liberals. Finally, when considering religious practices, those who reported attending to some religious services weekly indicated higher PA and SD than those who reported never attending. In conclusion, although the PA and SD in workers towards LG people are expressed in low levels, they continue to be present. A relatively high proportion of non-heterosexuals participating in the study (29 %) may have had an impact on the low levels of PA and SD found. This study provides relevant information about the attitudes of workers in relation to sexual minorities, which allows organizations to develop diversity programs that are more inclusive and LGBT-friendly.Mediante un estudio cuantitativo, exploratorio-descriptivo y no experimental, se examinóla actitud prejuiciada (AP) y el distanciamiento social (DS) hacia las personas lesbianas y gays (LG) en una muestra de trabajadores en Puerto Rico.&nbsp;La muestra estuvo compuesta por779 participantes, de los cuales 61&nbsp;%fueron mujeres entre el rango de edad de 21 a 40 años.&nbsp;Los resultados reflejaron&nbsp;que los trabajadores muestranniveles bajos de AP (M=85.47) y niveles&nbsp;bajos de&nbsp;DS (M=18.14) hacia las personas LG. Igualmente, encontramos una relación directa, moderadamente alta y significativa&nbsp;entre dichas variables,&nbsp;r&nbsp;(777) = .63,&nbsp;p&lt;.01.Al considerar la orientación sexual, los heterosexuales manifestaron mayor APy DS hacia las personas LG que los no-heterosexuales.&nbsp;Respecto a la perspectiva política, los conservadores manifestaron más AP y DS que los liberales.&nbsp;Por último, alconsiderar las prácticas religiosas, los que asisten semanalmente a algún servicio religioso mostraron mayor AP y DS que los que nunca van.&nbsp;En conclusión, aunque las AP y la DS de los trabajadores hacia las personas LG se manifiestan en niveles bajos, aún siguen presentes y son consistentes con otros estudios. Lo anterior representa serias implicaciones para el sector gay y lésbico en el contexto laboral. Al comparar este&nbsp;estudio con otros, éste provee información relevante del pensar de los trabajadores en relación a las minorías sexuales, aspecto no auscultado anteriormente y que permite a las organizaciones desarrollar programas de diversidad más inclusivos y LGBT-amigables.&nbsp