Production planning and scheduling optimization model: a case of study for a glass container company

Based on a case study, this paper deals with the production planning and scheduling problem of the glass con-tainer industry. This is a facility production system that has a set of furnaces where the glass is produced in order to meet the demand, being afterwards distributed to a set of parallel molding machines. Due to huge setup times involved in a color changeover, manufacturers adopt their own mix of furnaces and machines to meet the needs of their customers as flexibly and efficiently as possible. In this paper we proposed an optimization model that maximizes the fulfillment of the demand considering typical constraints from the planning production formulation as well as real case production constraints such as the limited product changeovers and the minimum run length in a machine. The complexity of the proposed model is assessed by means of an industrial real life problem

Integrated approach to assignment, scheduling and routing problems

This research considers a real life case study that determines the minimum number of sellers required to attend a set of customers located in a certain region taking into account the weekly schedule plan of the visits, as well as the optimal route. The problem is formulated as a combination of assignment, scheduling and routing problems. In the new formulation, case studies of small size subset of customers of the above type can be solved optimally. However, this subset of customers is not representative within the business plan of the company. To overcome this limitation, the problem is divided into three phases. A greedy algorithm is used in Phase I in order to identify a set of cost-effective feasible clusters of customers assigned to a seller. Phase II and III are then used to solve the problem of a weekly program for visiting the customers as well as to determine the route plan using MILP formulation. Several real life instances of different sizes have been solved demonstrating the efficiency of the proposed approach

Integrated Approach to Assignment, Scheduling and Routing Problems in a Sales Territory Business Plan

AbstractThis paper considers a real life case study that determines the minimum number of sellers required to attend a set of customers located in a certain region taking into account the weekly schedule plan of the visits, as well as the optimal route. The problem is formulated as a combination of assignment, scheduling and routing problems. In the new formulation, case studies of small size subset of customers of the above type can be solved optimally. However, this subset of customers is not representative within the business plan of the company. To overcome this limitation, the problem is divided into three phases. A greedy algorithm is used in Phase I in order to identify a set of cost-effective feasible clusters of customers assigned to a seller. Phase II and III are then used to solve the problem of a weekly program for visiting the customers as well as to determine the route plan using MILP formulation. Several real life instances of different sizes have been solved demonstrating the efficiency of the proposed approach

Valorization of toxic cyanobacteria biomass - disruption efficiency assessment and consequent bioproduct availability using different disruption techniques

The worldwide occurrence of hepatotoxic cyanobacterium Microcystis aeruginosa and accumulation of its toxin microcystin-LR, have been responsible for several human deaths and animal intoxication incidents. In recognition to its toxicity, the World Health Organization and several national governments established guideline values for this toxin in water, which gave rise to an increasing demand for microcystin′s analytical standards. These standards might be useful either as laboratory standards to apply in human and environmental risk assessment or as tools for molecular and cell biology studies. However, their availability is still limited due to constraints found in production and purification processes, which inflate the final price to values as high as 28000 €/mg. As an example of the increasing interest observed over the last years, U.S. Environmental Protection Agency has recently announced that cyanotoxins became part of its list of substances to be studied as a precursor to regulatory action between 2018 and 2020. Consequently, the optimization of this cyanobacterium cultivation and toxin purification techniques is needed to decrease the production cost of such high added-value product. In biotechnological industrial scale processes, the costs associated with downstream processing often represent more than 60 % of the overall expenses. The aim of this work is therefore to provide an insight regarding the development of a costeffective process for obtaining high-quality and affordable microcystin-LR by evaluating the efficiency of three different methodologies (microwave, freeze-thaw cycles and bead mill) on the disruption of M. aeruginosa and consequent availability of bioproducts. For that purpose, several parameters including time, power, and temperature were tested. The best conditions determined for each extraction method were the following: i) 1.5 minutes at 800 W (microwave), ii) three 12- hour cycles at -20 ºC (freeze-thaw cycles), and iii) 7 minutes using 20 % (v/v) of glass beads (bead mill). According to cell counting and intracellular organic matter release determining techniques, freeze-thaw cycles have shown to be the best disruption method presenting an overall efficiency around 97 %

Formación de celdas de manufacturas dinámicas para la toma de decisiones en el diseño de instalaciones industriales: una revisión

This paper presents a literature review with the purpose of characterizing the Dynamic Manufacturing Cell Formation Problem by means of the identification of optimization criteria, the most relevant restrictions needed for consideration and the most frequently used solution methods. Hence, an adaptation of the PRISMA statement was conducted for systematic reviews along with Snowball Methodology to select the studies to be analyzed. The document search is carried out in the Web of Science and Scopus databases, considering a time frame between 2007 and 2019. As a general result, it was found that cost minimization is the most frequently used optimization criterion and the typically considered constraints are associated with part machine operation sequence, machine breakdowns, and lot size. On the other hand, considering the highly combinatorial nature of the optimization problems reviewed, it was found that metaheuristics are the most used solution method, and genetic algorithms as well as simulated annealing are the most frequently implemented. Finally, three research trends are determined: incorporation of two or more optimization criteria in a mathematical formulation, development and implementation of hybrid metaheuristic algorithms, and comparison of performance of the existing solution methods based on reference problems or real industrial applications.Este artículo presenta una revisión de literatura con el fin de caracterizar el Problema de Formación de Celdas de Manufactura Dinámicas, realizando la identificación de los criterios de optimización, las principales restricciones consideradas y los métodos de solución más usados. Para ello, se condujo una adaptación de la declaración PRISMA para revisiones sistemáticas, en conjunto con una metodología bola de nieve para la selección de los estudios a analizar; la búsqueda de documentos se realiza en las bases de datos Web of Science y Scopus, considerando una ventana de tiempo entre 2007 y 2019. Como resultados generales, se encuentra que la minimización de costos es el criterio de optimización utilizado con mayor frecuencia y que las restricciones usualmente consideradas están asociadas a la secuencia de operaciones, averías de máquinas, y variación del tamaño de lote de procesamiento. De otra parte, considerando la naturaleza altamente combinatoria de los problemas de optimización revisados, se encuentra que los métodos de solución metaheurísticos utilizados en mayor medida son algoritmos genéticos, y recocido simulado. Finalmente, se determinan tres tendencias de investigación primero, la incorporación de dos o más criterios de optimización en una formulación matemática; segundo, el desarrollo e implementación de algoritmos metaheurísticos híbridos y; tercero, la evaluación de los métodos de solución existentes a partir de problemas de referencia o aplicaciones industriales reales

Isolated Grauer's gorilla populations differ in diet and gut microbiome

The animal gut microbiome has been implicated in a number of key biological processes, ranging from digestion to behavior, and has also been suggested to facilitate local adaptation. Yet studies in wild animals rarely compare multiple populations that differ ecologically, which is the level at which local adaptation may occur. Further, few studies simultaneously characterize diet and gut microbiome from the same sample, despite their likely interdependence. Here, we investigate the interplay between diet and gut microbiome in three geographically isolated populations of the critically endangered Grauer's gorilla, which we show to be genetically differentiated. We find population- and social group-specific dietary and gut microbial profiles and co-variation between diet and gut microbiome, despite the presence of core microbial taxa. There was no detectable effect of age, and only marginal effects of sex and genetic relatedness on the microbiome. Diet differed considerably across populations, with the high-altitude population consuming a lower diversity of plants compared to low-altitude populations, consistent with plant availability constraining diet. The observed pattern of covariation between diet and gut microbiome is likely a result of long-term social and environmental factors. Our study suggests that the gut microbiome is sufficiently plastic to support flexible food selection and hence contribute to local adaptation

Eradication of invasive species: science, attitude and understanding. The beaver in Tierra del Fuego

El manejo de especies invasoras presenta desafíos, que incluyen la necesidad de generar conocimiento aplicado y capacidades de gestión, así como modificar actitudes y comportamientos de la sociedad. El caso de la especie invasora castor canadiense, Castor canadensis, ejemplifica enfoques que pueden aplicarse para tratar otras especies invasoras. Repasamos la historia de manejo del castor y el cambio de enfoque que derivó en un acuerdo binacional inédito para restaurar los ecosistemas afectados por la especie mediante su erradicación, acuerdo que avanza mediante un proceso de generación de capacidades y escalamiento en la complejidad del trabajo, desde áreas piloto hacia todo el rango de distribución actual de la especie. Destacamos cómo la investigación aporta al manejo del castor, presentando detalles de la investigación en marcha en algunos ejes principales: 1) la factibilidad de erradicar en áreas piloto; 2) la estimación de tasas vitales y de dispersión y la construcción de modelos predictivos de expansión de la invasión, y 3) la determinación de criterios objetivos para declarar la erradicación del castor en sectores bajo manejo. La generación de capacidades es crucial para este complejo proceso. La construcción del capital social necesario para manejar el problema requiere de un diálogo continuo entre los diversos sectores involucrados y la construcción de agendas consensuadas. El sector científico puede asistir este proceso, pero sin imponer agendas unilaterales, sino identificando y contribuyendo a resolver las preguntas correctas y entendiendo las particularidades de los demás sectores, la cultura de las organizaciones y los tiempos para dar respuestas prácticas para lograr conservación basada en ciencia.The management of invasive species involves several challenges, ranging from the need to generate applied knowledge and capacity building abilities to a change in perceptions and behaviors in society. The case of the invasive Canadian beaver, Castor canadensis, illustrates possible approaches to address other invasive species. We reviewed the management history of the beaver and the change of approach that led to an unprecedented bi-national agreement to restore the affected ecosystems by means of the eradication of the species. This agreement advances by means of a training process of capacity building and a gradual scaling in the complexity of the work, from pilot areas to the whole current distribution of the species. We highlight how scientific research contributes to the management of the species, presenting details of the ongoing research in three major areas: 1) feasibility of eradication in pilot areas; 2) assessment of vital and dispersion rates and building predictive models of the spread of the invasion, and 3) determination of objective criteria to declare beaver eradication in areas under management. Capacity building is critical for this complex process. Assembling the social capital needed to manage the problem requires a continuous dialogue and agreed agendas among various stakeholders. The scientific sector can assist in this process without imposing unilateral agendas, but identifying the right questions and understanding the particularities of other sectors, the culture of organizations and the time frames needed for practical responses to achieve science-based conservation.Fil: Schiavini, Adrian Carlos Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Carranza, M. L.. Secretaria de Desarrollo Sustentable y Ambiente; ArgentinaFil: Deferrari, Guillermo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Escobar, Julio Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Malmierca, Laura Margarita Elvira. Administración de Parques Nacionales. Delegación Regional Patagonia; ArgentinaFil: Pietrek, A.. University of Duke; Estados Unido

Development of New Antiproliferative Compound against Human Tumor Cells from the Marine Microalgae Nannochloropsis gaditana by Applied Proteomics

Proteomics is a crucial tool for unravelling the molecular dynamics of essential biological processes, becoming a pivotal technique for basic and applied research. Diverse bioinformatic tools are required to manage and explore the huge amount of information obtained from a single proteomics experiment. Thus, functional annotation and protein-protein interactions are evaluated in depth leading to the biological conclusions that best fit the proteomic response in the system under study. To gain insight into potential applications of the identified proteins, a novel approach named "Applied Proteomics" has been developed by comparing the obtained protein information with the existing patents database. The development of massive sequencing technology and mass spectrometry (MS/MS) improvements has allowed the application of proteomics nonmodel microorganisms, which have been deeply described as a novel source of metabolites. Between them, Nannochloropsis gaditana has been pointed out as an alternative source of biomolecules. Recently, our research group has reported the first complete proteome analysis of this microalga, which was analysed using the applied proteomics concept with the identification of 488 proteins with potential industrial applications. To validate our approach, we selected the UCA01 protein from the prohibitin family. The recombinant version of this protein showed antiproliferative activity against two tumor cell lines, Caco2 (colon adenocarcinoma) and HepG-2 (hepatocellular carcinoma), proving that proteome data have been transformed into relevant biotechnological information. From Nannochloropsis gaditana has been developed a new tool against cancer-the protein named UCA01. This protein has selective effects inhibiting the growth of tumor cells, but does not show any effect on control cells. This approach describes the first practical approach to transform proteome information in a potential industrial application, named "applied proteomics". It is based on a novel bioalgorithm, which is able to identify proteins with potential industrial applications. From hundreds of proteins described in the proteome of N. gaditana, the bioalgorithm identified over 400 proteins with potential uses; one of them was selected as UCA01, "in vitro" and its potential was demonstrated against cancer. This approach has great potential, but the applications are potentially numerous and undefined

The balance between antibiotic resistance and fitness/virulence in Pseudomonas aeruginosa: an update on basic knowledge and fundamental research

The interplay between antibiotic resistance and bacterial fitness/virulence has attracted the interest of researchers for decades because of its therapeutic implications, since it is classically assumed that resistance usually entails certain biological costs. Reviews on this topic revise the published data from a general point of view, including studies based on clinical strains or in vitro-evolved mutants in which the resistance phenotype is seen as a final outcome, i.e., a combination of mechanisms. However, a review analyzing the resistance/fitness balance from the basic research perspective, compiling studies in which the different resistance pathways and respective biological costs are individually approached, was missing. Here we cover this gap, specifically focusing on Pseudomonas aeruginosa, a pathogen that stands out because of its extraordinary capacity for resistance development and for which a considerable number of recent and particular data on the interplay with fitness/virulence have been released. The revised information, split into horizontally-acquired vs. mutation-driven resistance, suggests a great complexity and even controversy in the resistance-fitness/virulence balance in the acute infection context, with results ranging from high costs linked to certain pathways to others that are seemingly cost-free or even cases of resistance mechanisms contributing to increased pathogenic capacities. The elusive mechanistic basis for some enigmatic data, knowledge gaps, and possibilities for therapeutic exploitation are discussed. The information gathered suggests that resistance-fitness/virulence interplay may be a source of potential antipseudomonal targets and thus, this review poses the elementary first step for the future development of these strategies harnessing certain resistance-associated biological burdens

Leigh syndrome is the main clinical characteristic of PTCD3 deficiency

Mitochondrial translation defects are a continuously growing group of disorders showing a large variety of clinical symptoms including a wide range of neurological abnormalities. To date, mutations in PTCD3, encoding a component of the mitochondrial ribosome, have only been reported in a single individual with clinical evidence of Leigh syndrome. Here, we describe three additional PTCD3 individuals from two unrelated families, broadening the genetic and phenotypic spectrum of this disorder, and provide definitive evidence that PTCD3 deficiency is associated with Leigh syndrome. The patients presented in the first months of life with psychomotor delay, respiratory insufficiency and feeding difficulties. The neurologic phenotype included dystonia, optic atrophy, nystagmus and tonic-clonic seizures. Brain MRI showed optic nerve atrophy and thalamic changes, consistent with Leigh syndrome. WES and RNA-seq identified compound heterozygous variants in PTCD3 in both families: c.[1453-1G>C];[1918C>G] and c.[710del];[902C>T]. The functional consequences of the identified variants were determined by a comprehensive characterization of the mitochondrial function. PTCD3 protein levels were significantly reduced in patient fibroblasts and, consistent with a mitochondrial translation defect, a severe reduction in the steady state levels of complexes I and IV subunits was detected. Accordingly, the activity of these complexes was also low, and high-resolution respirometry showed a significant decrease in the mitochondrial respiratory capacity. Functional complementation studies demonstrated the pathogenic effect of the identified variants since the expression of wild-type PTCD3 in immortalized fibroblasts restored the steady-state levels of complexes I and IV subunits as well as the mitochondrial respiratory capacity. Additionally, minigene assays demonstrated that three of the identified variants were pathogenic by altering PTCD3 mRNA processing. The fourth variant was a frameshift leading to a truncated protein. In summary, we provide evidence of PTCD3 involvement in human disease confirming that PTCD3 deficiency is definitively associated with Leigh syndrome.© 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology