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The Oven Scheduling Problem (OSP) is a new parallel batch scheduling problem that arises in the area of electronic component manufacturing. Jobs need to be scheduled to one of several ovens and may be processed simultaneously in one batch if they have compatible requirements. The scheduling of jobs must respect several constraints concerning eligibility and availability of ovens, release dates of jobs, setup times between batches as well as oven capacities. Running the ovens is highly energy-intensive and thus the main objective, besides finishing jobs on time, is to minimize the cumulative batch processing time across all ovens. This objective distinguishes the OSP from other batch processing problems which typically minimize objectives related to makespan, tardiness or lateness. We propose to solve this NP-hard scheduling problem using exact techniques and present two different modelling approaches, one based on batch positions and another on representative jobs for batches. These models are formulated as constraint programming (CP) and integer linear programming (ILP) models and implemented both in the solver-independent modeling language MiniZinc and using interval variables in CP Optimizer. An extensive experimental evaluation of our solution methods is performed on a diverse set of problem instances. We evaluate the performance of several state-of-the-art solvers on the different models and on three variants of the objective function that reflect different real-life scenarios. We show that our models can find feasible solutions for instances of realistic size, many of those being provably optimal or nearly optimal solutions.

The Oven Scheduling Problem (OSP) is a new parallel batch scheduling problem that arises in the area of electronic component manufacturing. Jobs need to be scheduled to one of several ovens and may be processed simultaneously in one batch if they have compatible requirements. The scheduling of jobs must respect several constraints concerning eligibility and availability of ovens, release dates of jobs, setup times between batches as well as oven capacities. Running the ovens is highly energy-intensive and thus the main objective, besides finishing jobs on time, is to minimize the cumulative batch processing time across all ovens. This objective distinguishes the OSP from other batch processing problems which typically minimize objectives related to makespan, tardiness or lateness. We propose to solve this NP-hard scheduling problem via constraint programming (CP) and integer linear programming (ILP) and present corresponding models. For an experimental evaluation, we introduce a multi-parameter random instance generator to provide a diverse set of problem instances. Using state-of-the-art solvers, we evaluate the quality and compare the performance of our CP- and ILP-models. We show that our models can find feasible solutions for instances of realistic size, many of those being provably optimal or nearly optimal solutions. Finally, we derive theoretical lower bounds on the solution cost of feasible solutions to the OSP; these can be computed within a few seconds. We show that these lower bounds are competitive with those derived by state-of-the-art solvers.

Sewage sludge (SS) has been connected to a variety of global environmental problems. Assessing the risk of various disposal techniques can be quite useful in recommending appropriate management. The preparation of sewage sludge biochar (SSB) and its impacts on soil characteristics, plant health, nutrient leaching, and greenhouse gas emissions (GHGs) are critically reviewed in this study. Comparing the features of SSB obtained at various pyrolysis temperatures revealed changes in its elemental content. Lower hydrogen/carbon ratios in SSB generated at higher pyrolysis temperatures point to the existence of more aromatic carbon molecules. Additionally, the preparation of SSB has an increased ash content, a lower yield, and a higher surface area as a result of the rise in pyrolysis temperature. The worldwide potential of SS output and CO2-equivalent emissions in 2050 were predicted as factors of global population and common disposal management in order to create a futuristic strategy and cope with the quantity of abundant global SS. According to estimations, the worldwide SS output and associated CO2-eq emissions were around 115 million tons dry solid (Mt DS) and 14,139 teragrams (Tg), respectively, in 2020. This quantity will rise to about 138 Mt DS sewage sludge and 16985 Tg CO2-eq emissions in 2050, a 20% increase. In this regard, developing and populous countries may support economic growth by utilizing low-cost methods for producing biochar and employing it in local agriculture. To completely comprehend the benefits and drawbacks of SSB as a soil supplement, further study on long-term field applications of SSB is required.

Chemical nitrogen (N) fertilizers are regarded as one of the environmental contaminants in addition to the necessity for fossil sources for their production. Conversely, it is impossible to neglect the supply of nitrogen needed as one of the essential ingredients for plant function. For organic agriculture, it is crucial to use alternative fertilizer management to reduce the harmful impacts and production costs of chemical fertilizers. In a one-year pot experiment, nitrate (NO−3) leaching and nitrogen efficiency of wheat were examined in relation to biochar (B) mixed with urea (U), legume residues (L), and azocompost (A), which represent chemical, green, and biological sources of N-fertilizers, respectively. Control (no biochar, no fertilizer), U (46 kg ha−1), A (5 t ha−1), L (5 t ha−1), B (10 t ha−1), UB, AB, and LB were the experimental treatments. Grain yield of wheat was enhanced by 337% and 312% with UB and UL, respectively. The LB produced the highest grain N yield, with a rise of 8.8 times over the control. L had the highest N-use efficiency, with an increase of 149% over the control. The highest N-harvest index and N-recovery efficiency were obtained by using LB, with values of 91 and 70 %, respectively. Nitrate leaching occurred in the following order: U > Control ≥ A ≥ L > UB > AB ≥ LB > B. Nitrogen is retained for the plant in the extensive specific surface of biochar when N-fertilizers are used in conjunction with them. This not only improves N-efficiency but also minimizes nitrogen loss through leaching. Additionally, the soil can benefit from the addition of leguminous organic fertilizer in a similar way as to urea fertilizer in terms of increasing wheat grain yield, particularly when combined with biochar.

Though copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI. We performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings. Of the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by CMA alone, including two likely changes. Three (2.2%) participants had diagnostic molecular findings from both ES and CMA, including two compound heterozygotes and one participant with two distinct diagnoses. Half of the participants with CMA contribution to diagnosis had CNVs in at least one non-immune gene, highlighting the clinical complexity of these cases. Overall, CMA contributed to 18/134 diagnoses (13.4%), increasing the overall diagnostic yield by 15.5% beyond ES alone. Pairing ES and CMA can provide a comprehensive evaluation to clarify the complex factors that contribute to both immune and non-immune phenotypes. Such a combined approach to genetic testing helps untangle complex phenotypes, not only by clarifying the differential diagnosis, but in some cases by identifying multiple diagnoses contributing to the overall clinical presentation.

This paper discusses the current status of the European research reactor (RR) fleet and identified opportunities for its utilization. The data for this analysis was collected through a specific questionnaire from which a database of the European RR fleet was created. The questionnaire was designed to assess the degree of exploitation of different RR applications and to identify gaps and opportunities for future utilization. The results indicate that the European RR fleet is older compared to the world average, with no new research reactors built in Europe since 1992. The majority of RRs reported low levels of exploitation across all applications, and a desire to expand utilization was expressed by 78% of respondents. Lack of manpower, finance, and customers were identified as the main obstacles preventing expansion, while the need for more nuclear engineers was identified as a clear opportunity to attract people to the field. The findings of this study emphasize the need for actions to be taken to combat future needs and to improve the utilization of the European RR fleet. Overall, this study provides valuable insights for policymakers, industry professionals, and researchers working in the field of nuclear energy.

Background Large-scale cohort-based whole exome sequencing of individuals with neurodevelopmental disorders (NDDs) has identified numerous novel candidate disease genes; however, detailed phenotypic information is often lacking in such studies. De novo mutations in pogo transposable element with zinc finger domain ( POGZ ) have been identified in six independent and diverse cohorts of individuals with NDDs ranging from autism spectrum disorder to developmental delay. Methods Whole exome sequencing was performed on five unrelated individuals. Sanger sequencing was used to validate variants and segregate mutations with the phenotype in available family members. Results We identified heterozygous truncating mutations in POGZ in five unrelated individuals, which were confirmed to be de novo or not present in available parental samples. Careful review of the phenotypes revealed shared features that included developmental delay, intellectual disability, hypotonia, behavioral abnormalities, and similar facial characteristics. Variable features included short stature, microcephaly, strabismus and hearing loss. Conclusions While POGZ has been associated with neurodevelopmental disorders in large cohort studies, our data suggest that loss of function variants in POGZ lead to an identifiable syndrome of NDD with specific phenotypic traits. This study exemplifies the era of human reverse clinical genomics ushered in by large disease-directed cohort studies; first defining a new syndrome molecularly and, only subsequently, phenotypically.

Embryonic development occurs through commitment of pluripotent stem cells to differentiation programs that require highly coordinated changes in gene expression. Chromatin remodeling of gene regulatory elements is a critical component of how such changes are achieved. While many factors controlling chromatin dynamics are known, mechanisms of how different chromatin regulators are orchestrated during development are not well understood. Here, we describe LINKED (LINKage-specific-deubiquitylation-deficiency-induced Embryonic Defects) syndrome, a novel multiple congenital anomaly disorder caused by hypomorphic hemizygous missense variants in the deubiquitylase OTUD5/DUBA. Studying LINKED mutations in vitro, in mouse, and in models of neuroectodermal differentiation of human pluripotent stem cells, we uncover a novel regulatory circuit that coordinates chromatin remodeling pathways during early differentiation. We show that the K48-linkage-specific deubiquitylation activity of OTUD5 is essential for murine and human development and, if reduced, leads to aberrant cell-fate specification. OTUD5 controls differentiation through preventing the degradation of multiple chromatin regulators including ARID1A/B and HDAC2, mutation of which underlie developmental syndromes that exhibit phenotypic overlap with LINKED patients. Accordingly, loss of OTUD5 during early differentiation leads to less accessible chromatin at neural and neural crest enhancers and thus aberrant rewiring of gene expression networks. Our work identifies a novel mechanistic link between phenotypically related developmental disorders and an essential function for linkage-specific ubiquitin editing of substrate groups (i.e. chromatin remodeling complexes) during early cell-fate decisions; a regulatory concept, we predict to be a general feature of embryonic development.