Optimization model for production scheduling taking into account preventive maintenance in an uncertainty-based production system.

In the dynamic yet uncertain environment of Industry 4.0, industrial companies are utilizing the benefits of contemporary technologies in manufacturing by striving to implement optimization models in each stage of the decision-making process. Many organizations are focusing particularly on the optimization of two key aspects of the manufacturing process - production schedules and maintenance plans. This article presents a mathematical model with the main advantage of finding a valid production schedule (if such exists) for the distribution of individual production orders on the available production lines over a specified period. The model further considers the scheduled preventive maintenance activities on the production lines, as well as the preferences of the production planners regarding the start of the production orders and non-use of certain machines. When necessary, it also offers the possibility to make timely changes in the production schedule, and thus to handle the uncertainty as precisely as possible. For the verification of the model, two experiments were conducted (quasi-real and real-life), with data from a discrete automotive manufacturer of locking systems. The results from the sensitivity analysis demonstrated that the model further optimizes the execution times of all orders, and specifically the production lines usage - their optimal load and non-use of unnecessary machines (valid plan with 4 out of 12 lines not used). This allows for cost savings and raises the overall efficiency of the production process. Thus, the model adds value for the organization by presenting a production plan with optimal machine usage and product allocation. If incorporated into an ERP system, it could distinctly save time and streamline the production scheduling process.

Diet restriction alone improves glucose tolerance and insulin sensitivity than its coadministration with krill or fish oil in a rabbit model of castration-induced obesity.

This study investigated the effect of 50% diet restriction and its coadministration with krill oil (KO) or fish oil (FO) on glucose tolerance and insulin sensitivity in a rabbit model of obesity. Castrated male rabbits were 50% restricted fed and supplemented with KO or FO (600 mg omega-3 polyunsaturated fatty acids/daily) for 2 months. Simultaneously, two control groups were used: castrated, full-diet-fed and castrated, 50% restricted fed rabbits without additives restricted group (RG). The energy-restricted diet decreased final body weight in castrated male rabbits and improved most insulin sensitivity and ß-cell function indexes. Combining the same diet and KO or FO, further reduced fasting blood glucose levels. However, this feed regime significantly accelerated insulin secretion and reduced gene expression of insulin receptor substrate-1, pyruvate kinase and 3-hydroxy-3-methylglutaryl-CoA synthase 2. This was manifested by reduced dynamic insulin sensitivity, assessment homoeostasis-ß-cell function indices and increased glucose elimination rate to levels comparable to or above the obese animals. Aspartate and alanine aminotransferases enzyme activities were raised more than those in the obese group. Surprisingly, KO and FO administration downregulated acetyl-coenzyme A oxidase and carnitine palmitoyltransferase 2 messenger RNA gene expression compared to the RG. In conclusion, we can assume that a better effect on insulin sensitivity and glucose tolerance was observed in the diet restriction alone than in the coadministration of KO or FO when animals are exposed to highly obesity predisposing factors. These effects could be at least in part ascribed to the modified gene expression levels of some critical enzymes and factors involved in liver glucose metabolism and ß-oxidation.

Sintered Glass-Ceramics, Self-Glazed Materials and Foams from Metallurgical Waste Slag.

The materials used for the synthesis of parent glass are 70% wt. metallurgical slag and 30% wt. industrial quartz sand. The initial batch is melted at and then quenched in water. The resulting glass frit is milled bellow 75 microns and pressed 1400 °C into "green" samples. In a next stage, they are heat treated at different temperatures with various heating rates and holding times. As a result, it is demonstrated the possibility for production variations, allowing the manufacture of three types of new materials by using the same pressed glass powders. We highlight the flexibility of the synthesis obtaining namely well densified glass-ceramics at about 950 °C, self-glazed glass-ceramics at about 1000 °C or glass-ceramic foams at approximately 1100 °C. The first set of materials is characterized by very well sintered structure combined with reasonable crystallinity; the second one-by smooth self-glazed surface with an attractive appearance and good properties and the third one-by 80-90% closed porosity and very good thermal stability above 1000 °C.

Impact of Resolution and Texture of Laser Scanning Generated Three-Dimensional Models on Landmark Identification.

The aim of the study was to determine the impact of the resolution and texture of three-dimensional (3D) models created through laser scanning on the measurement error (ME) of craniometric landmarks. Ten skulls were scanned at five different resolutions, and the generated 3D models were exported with and without texture. The 3D coordinates of 28 landmarks were derived. Each landmark was picked five times by one observer. The ME of a definite landmark was calculated as an average of distances between the repeated placements of the landmark by the observer and the landmark centroid. One-way analysis of variance was applied for detection of significant differences in the MEs between and within landmark types recorded at different resolutions. The MEs of landmark types in textured and nontextured models were compared by a paired test. Twelve linear measurements were calculated as interlandmark distances, and their values obtained on the models of different resolution were compared. The Frankfurt horizontal plane was constructed for each model and its deviation was calculated at different resolutions. Scan resolution impacted MEs of Type 1 and Type 2 landmarks but not the precision level of Type 3 landmarks. Texture most influenced the precise identification of Type 1 landmarks. The interlandmark distances between Type 2 landmarks were most consistent in their values, those between Type 1 landmarks showed deviations in low-resolution models, and distances between Type 3 landmarks demonstrated various patterns of transition of the values throughout the resolutions. Altogether, the use of textured high-resolution models would be preferable in morphometric studies. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1950-1965, 2020. © 2019 American Association for Anatomy.

Sagittal suture maturation: Morphological reorganization, relation to aging, and reliability as an age-at-death indicator.

OBJECTIVES: The sagittal suture (SS) is assumed to be an initial site for the commencement of cranial suture closure as well as the most frequent spot of isolated craniosynostosis. The present study aimed to inspect the reorganization of the SS at the microlevel to assess the relation between its closure and aging and to establish whether it could be used as a reliable indicator in age-at-death prediction. MATERIALS AND METHODS: The SS was investigated in 68 dry contemporary adult male skulls of known age-at-death. An additional series of 20 skulls was used for verification. The skulls were scanned using a micro-computed tomography system. The SS closure degree was assessed along the three bone layers on cross-sectional tomograms by using a scoring scale. RESULTS: In the entirely open SS, the bone edges consist of compact bone and are widely separated. With SS maturation, the bone edges come into contact, and the remodeling process leads to a decrease in the sutural area and bone homogenization across all three layers. SS closure is an irregular process roughly related to aging, beginning in the early 20s, reaching its peak at about 30 years of age and abating in the late 40s. DISCUSSION: Although related to aging, SS closure is not a simple function of it. Rather, the underlying factors inducing and managing this process are multifaceted and complex. Although the etiology of SS maturation remains unclear, it is reasonable to use SS closure cautiously and only as a supportive method for age prediction.

n-3 polyunsaturated fatty acids provoke a specific transcriptional profile in rabbit adipose-derived stem cells in vitro.

Adipose-derived stem cells (ADSCs) possess multipotent properties, and their proper functionality is essential for further development of metabolic disorders. In the current study, we explored the impact of two n-3 LC-PUFAs (long-chain polyunsaturated fatty acids, DHA-docosahexaenoic; C22:6, and EPA-eicosapentaenoic; C20:5) on a specific profile of lipolytic-related gene expressions in the in vitro-differentiated subcutaneous and visceral ADSCs from rabbits. The subcutaneous and visceral ADSCs were obtained from 28-day-old New Zealand rabbits. The primary cells were cultured up to passage 4 and were induced for adipogenic differentiation. Thereafter, the differentiated cells were treated with 100 µg EPA or DHA for 48 hr. The total mRNA was isolated and target genes expression evaluated by real-time RCR. The results demonstrated that treatment of rabbit ADSCs with n-3 PUFAs significantly enhanced mRNA expression of Perilipin A, while the upregulation of leptin and Rab18 genes was seen mainly in ADSCs from visceral adipose tissue. Moreover, the EPA significantly enhanced PEDF (Pigment Derived Epithelium Factor) mRNA expression only in visceral cells. Collectively, the results suggest activation of an additional lipolysis pathway most evident in visceral cells. The data obtained in our study indicate that in vitro EPA up-regulates the mRNA expression of the studied lipolysis-associated genes stronger than DHA mainly in visceral rabbit ADSCs.

Oxygen Perfusion (Persufflation) of Human Pancreata Enhances Insulin Secretion and Attenuates Islet Proinflammatory Signaling.

BACKGROUND: All human islets used in research and for the clinical treatment of diabetes are subject to ischemic damage during pancreas procurement, preservation, and islet isolation. A major factor influencing islet function is exposure of pancreata to cold ischemia during unavoidable windows of preservation by static cold storage (SCS). Improved preservation methods may prevent this functional deterioration. In the present study, we investigated whether pancreas preservation by gaseous oxygen perfusion (persufflation) better preserved islet function versus SCS. METHODS: Human pancreata were preserved by SCS or by persufflation in combination with SCS. Islets were subsequently isolated, and preparations in each group matched for SCS or total preservation time were compared using dynamic glucose-stimulated insulin secretion as a measure of ß-cell function and RNA sequencing to elucidate transcriptomic changes. RESULTS: Persufflated pancreata had reduced SCS time, which resulted in islets with higher glucose-stimulated insulin secretion compared to islets from SCS only pancreata. RNA sequencing of islets from persufflated pancreata identified reduced inflammatory and greater metabolic gene expression, consistent with expectations of reducing cold ischemic exposure. Portions of these transcriptional responses were not associated with time spent in SCS and were attributable to pancreatic reoxygenation. Furthermore, persufflation extended the total preservation time by 50% without any detectable decline in islet function or viability. CONCLUSIONS: These data demonstrate that pancreas preservation by persufflation rather than SCS before islet isolation reduces inflammatory responses and promotes metabolic pathways in human islets, which results in improved ß cell function.

Sex estimation by size and shape of foramen magnum based on CT imaging.

Foramen magnum (FM) has a well-protected position, which makes it of particular interest in forensic research. The aim of the study is to assess the sex differences in size and shape of FM, develop discriminant functions and logistic regression models based on the FM measurements, compare the accuracy results of the measurements obtained through different measuring approaches, and establish the most reliable variables for sex estimation in Bulgarian adults. Head CT scans of 140 Bulgarian adults were used in the study. The segmentation of the skulls was performed in the software InVesalius. The length, breadth, circumference, and area were measured based on the 3D coordinates of definite landmarks and semi-landmarks. The circumference and area were calculated regarding the foramen as a 2D and 3D structure. Two additional variables (λ2 and λ3) corresponding to the least square errors along the length and breadth directions at the fitting of the 3D coordinates to a plane were examined for their sex discriminating ability. The FM shape was classified based on the values of the FM index. The significance of the sex differences was assessed. Discriminate function analysis and binary logistic regression were conducted. Significant sex differences were established in the FM size and shape. The eigenvalue λ3 is the best discriminating parameter applying discriminant function analysis. The acceptance of FM as a 2D or 3D structure does not provide substantial information for its sex discrimination. The measurements of FM do not offer sufficiently high predicting rates for sex estimation in the Bulgarian population.

Digital radiomorphometric analysis of the frontal sinus and assessment of the relation between persistent metopic suture and frontal sinus development.

OBJECTIVES: This study aimed to establish the frequency of the frontal sinus (FS) aplasia, to compare metopic and nonmetopic series and thus to assess the relationship between the preservation of metopic suture and FS development. MATERIALS AND METHODS: FSs were investigated in 230 dry skulls of adult males distributed into control (137) and metopic (93) series. They were visualized through industrial digital radiography. RESULTS: In the control series, the FS aplasia was observed in 12.41% of the skulls, and it was mostly unilateral (8.76%) than bilateral (3.65%). The left-sided aplasia (5.11%) slightly prevailed over the right-sided one (3.65%). In the metopic series, the aplasia was observed with a frequency of 19.35%, and the bilateral aplasia (7.53%) was rarer that the unilateral one (11.83%), while the right-sided aplasia was clearly predominant (9.68%) compared to the left-sided one (2.15%). DISCUSSION: The significant differences between both series showed a tendency for the persistence of metopic suture to be frequently related with FS underdevelopment in the vertical plate of the frontal bone, but in cases of pneumatization, it was preferentially on the left side. Taking into account that the cranial hypertension leads to suture diastasis and hinders development of the FS, it could be suggested that persistence of the metopic suture along with underdevelopment of the FS in nonsyndromic adults could be an expression of an elevated intracranial pressure during early development as an after-effect of certain condition.

ExCAPE-DB: an integrated large scale dataset facilitating Big Data analysis in chemogenomics.

Chemogenomics data generally refers to the activity data of chemical compounds on an array of protein targets and represents an important source of information for building in silico target prediction models. The increasing volume of chemogenomics data offers exciting opportunities to build models based on Big Data. Preparing a high quality data set is a vital step in realizing this goal and this work aims to compile such a comprehensive chemogenomics dataset. This dataset comprises over 70 million SAR data points from publicly available databases (PubChem and ChEMBL) including structure, target information and activity annotations. Our aspiration is to create a useful chemogenomics resource reflecting industry-scale data not only for building predictive models of in silico polypharmacology and off-target effects but also for the validation of cheminformatics approaches in general.

Effect of fish and krill oil supplementation on glucose tolerance in rabbits with experimentally induced obesity.

PURPOSE: This study was conducted to investigate the effect of fish oil (FO) and krill oil (KO) supplementation on glucose tolerance in obese New Zealand white rabbits. METHODS: The experiments were carried out with 24 male rabbits randomly divided into four groups: KO-castrated, treated with KO; FO-castrated, treated with FO; C-castrated, non-treated; NC-non-castrated, non-treated. At the end of treatment period (2 months), an intravenous glucose tolerance test (IVGTT) was performed in all rabbits. RESULTS: Fasting blood glucose concentrations in FO and KO animals were significantly lower than in group C. The blood glucose concentrations in FO- and KO-treated animals returned to initial values after 30 and 60 min of IVGTT, respectively. In liver, carnitine palmitoyltransferase 2 (Cpt2) and 3-hydroxy-3-methyl-glutaryl-CoA synthase 2 (Hmgcs2) genes were significantly increased in FO-fed rabbits compared with the C group. Acetyl-CoA carboxylase alpha (Acaca) expression was significantly reduced in both KO- and FO-fed rabbits. In skeletal muscle, Hmgcs2 and Cd36 were significantly higher in KO-fed rabbits compared with the C group. Acaca expression was significantly lower in KO- and FO-fed rabbits compared with the C group. CONCLUSION: The present results indicate that FO and KO supplementation decreases fasting blood glucose and improves glucose tolerance in obese New Zealand white rabbits. This could be ascribed to the ameliorated insulin sensitivity and insulin secretion and modified gene expressions of some key enzymes involved in ß-oxidation and lipogenesis in liver and skeletal muscle.

Effects of castration-induced visceral obesity and antioxidant treatment on lipid profile and insulin sensitivity in New Zealand white rabbits.

Molecular mechanisms, responsible for the impaired insulin-sensitivity state due to the obesity are not fully understood in both humans and animals. The purpose of this study was to investigate the effects of castration-induced visceral obesity and the influence of two antioxidants on constituents of blood lipid profile and insulin sensitivity in New Zealand white rabbits. Twenty-six clinically healthy male New Zealand white rabbits were used in the experiment and were divided into 3 groups: first group (CI, n=7) - castrated-obese and treated with antioxidants "Immunoprotect" for 2months; second group (CO, n=7) - castrated-obese; third group (NC, n=12) - control group (non-castrated, non-obese). At the end of the follow-up period of 2months after castration an intravenous glucose tolerance test (IVGTT) was performed after a 12-h fasting period as the blood samples for determination of glucose and insulin and their kinetic parameters were obtained at 5 and 0min before and at 5, 10, 30, 60 and 120min after the infusion of the glucose. The constituents of lipid profile, triglycerides (TG), total cholesterol (TC) and HDL-cholesterol (HDL-C) were also assessed in the overnight fasting blood samples. The body weight (BW), body mass index (BMI), amount of the visceral fat (VF) and VF/BW ratio were both measured and calculated before the IVGTT and at the end of the experimental period. All measured markers of obesity (BW, BMI, VF, VF/BW) were significantly higher in both groups of castrated rabbits than in the control group. Apart HDL-C, the plasma concentrations of all constituents of lipid profile (TG, TC, HDL-C) were the highest in CO group. There were generally no differences between CI and NC groups for the same traits. After glucose injection blood glucose concentrations and glucose and insulin kinetic parameters were considerably higher (except of glucose elimination rate) in CO rabbits than in NC ones. Castrated rabbits treated with "Immunoprotect" showed lower fasting plasma insulin and improved glucose kinetics dynamics than CO rabbits, but commensurable values of glucose and insulin kinetics parameters than NC group. The results of the current study clearly indicated that castration-induced visceral obesity affected negatively the lipid profile and insulin sensitivity and/or responsiveness. Treatment with antioxidant supplementation, consisted of d-limonene and vitamin E, improved blood lipid profile, fatty liver, glucose homeostasis and insulin sensitivity in obese rabbits. In addition, based on our results we may suggest that castrated male New Zealand white rabbits might be considered as an appropriate animal model to study various metabolic abnormalities related to visceral obesity, such as dyslipidemia and impaired insulin sensitivity.

Stereospecific and quantitative photodimerisation of terminal olefins in the solid state.

Reaction of 4-vinylpyridine with AgClO(3) yields a crystalline solid that supports a stereospecific and quantitative [2+2] photodimerisation of two terminal olefins. Structural dynamics of the -CH[double bond, length as m-dash]CH(2) group, nature of the counterion, and extended packing influence the photoreactivity.

High-fat feeding and Staphylococcus intermedius infection impair beta cell function and insulin sensitivity in mongrel dogs.

As obesity is a state of low-grade inflammation, we aimed to investigate the combined effect of high-fat diet and bacterial infection on beta-cell function and insulin sensitivity in dogs. We used 20 healthy, male, mongrel dogs randomly divided into four groups: control group-healthy, non-obese dogs; infected group-non-obese dogs with experimentally induced infection (Staphylococcus intermedius); obese group-obese dogs (after 90 day high-fat diet) and obese-infected group-obese dogs with experimentally induced infection (Staphylococcus intermedius). To evaluate insulin sensitivity and beta-cell function an intravenous glucose tolerance test (IVGTT) was performed. Plasma insulin increased in all group after glucose infusion. The lowest values were found in obese-infected group. Blood glucose also increased on 3 min after glucose infusion and then gradually decreased. In obese-infected group glucose concentration on 30 min was still significantly higher than initial levels, while in other groups glucose concentration returned to the initial values. The lowest rate of glucose elimination was found in infected group. In dogs of obese group and obese-infected group AUC(ins 0-60 min) was lower compared to controls. AUC(glucose 0-60 min) values were lowest in infected group, while in obese-infected group values were the highest. Levels of I/G in dogs of obese-infected group were significantly lower compared to controls and infected group. In conclusion, these results reveal that infection in obese dogs leads to impaired glucose tolerance, which is result of impairment in both insulin secretion and insulin sensitivity.

Design and activity of a murine and humanized anti-CEACAM6 single-chain variable fragment in the treatment of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease, with surgery being the only curative modality for localized disease, and gemcitabine with or without erlotinib remains the standard of therapy for unresectable or metastatic disease. CEACAM6 is overexpressed in human PDA independent of stage or grade and causes anoikis resistance when dysregulated. Because murine monoclonal antibody 13-1 possesses target-specific cytotoxicity in human PDA cell lines, we designed a humanized anti-CEACAM6 single-chain variable fragment (scFv) based on monoclonal antibody 13-1. PEGylation of the glycine-serine linker was used to enhance plasma half-life. These scFvs bound CEACAM6 with high affinity, exhibited cytotoxic activity, and induced dose-dependent poly(ADP-ribose) polymerase cleavage. Murine PDA xenograft models treated with humanized scFv alone elicited tumor growth inhibition, which was enhanced in combination with gemcitabine. Immunohistochemistry showed significant apoptosis, with inhibition of angiogenesis and proliferation, and preservation of the target. Collectively, our results have important implications for the development of novel antibody-based therapies against CEACAM6 in PDA.

Supramolecular control of reactivity in the solid state: from templates to ladderanes to metal-organic frameworks.

We describe how reactivity can be controlled in the solid state using molecules and self-assembled metal-organic complexes as templates. Being able to control reactivity in the solid state bears relevance to synthetic chemistry and materials science. The former offers a promise to synthesize molecules that may be impossible to realize from the liquid phase while also taking advantage of the benefits of conducting highly stereocontrolled reactions in a solvent-free environment (i.e., green chemistry). The latter provides an opportunity to modify bulk physical properties of solids (e.g., optical properties) through changes to molecular structure that result from a solid-state reaction. Reactions in the solid state have been difficult to control owing to frustrating effects of molecular close packing. The high degree of order provided by the solid state also means that the templates can be developed to determine how principles of supramolecular chemistry can be generally employed to form covalent bonds. The paradigm of synthetic chemistry employed by Nature is based on integrating noncovalent and covalent bonds. The templates assemble olefins via either hydrogen bond or coordination-driven self-assembly for intermolecular [2 + 2] photodimerizations. The olefins are assembled within discrete, or finite, self-assembled complexes, which effectively decouples chemical reactivity from effects of crystal packing. The control of the solid-state assembly process affords the supramolecular construction of targets in the form of cyclophanes and ladderanes. The targets form stereospecifically, in quantitative yield, and in gram amounts. Both [3]- and [5]-ladderanes have been synthesized. The ladderanes are comparable to natural ladderane lipids, which are a new and exciting class of natural products recently discovered in anaerobic marine bacteria. The organic templates function as either hydrogen bond donors or hydrogen bond acceptors. The donors and acceptors generate cyclobutanes lined with pyridyl and carboxylic acid groups, respectively. The metal-organic templates are based on Zn(II) and Ag(I) ions. The reactivity involving Zn(II) ions is shown to affect optical properties in the form of solid-state fluorescence. The solids based on both the organic and metal-organic templates undergo rare single-crystal-to-single-crystal reactions. We also demonstrate how the cyclobutanes obtained from this method can be applied as novel polytopic ligands of metallosupramolecular assemblies (e.g., self-assembled capsules) and materials (e.g., metal-organic frameworks). Sonochemistry is also used to generate nanostructured single crystals of the multicomponent solids or cocrystals based on the organic templates. Collectively, our observations suggest that the organic solid state can be integrated into more mainstream settings of synthetic organic chemistry and be developed to construct functional crystalline solids.

Metal-mediated reactivity in the organic solid state: from self-assembled complexes to metal-organic frameworks.

The purpose of this tutorial review is to address the use of metal ions to mediate reactions in the organic solid state. We describe metal complexes and coordination networks that facilitate dimerizations, oligomerizations and polymerizations of olefins and acetylenes via irradiation (e.g. ultraviolet (UV) and (60)Co gamma-rays) and thermal annealing. We show how metal ions can be utilized to direct the formation of polymers and molecules. We also describe how supramolecular chemistry has recently influenced dimerization processes in self-assembled metal-organic solids.

MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment.

The cytokine macrophage migration inhibitory factor (MIF) plays a critical role in inflammatory diseases and atherogenesis. We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF. MIF triggered G(alphai)- and integrin-dependent arrest and chemotaxis of monocytes and T cells, rapid integrin activation and calcium influx through CXCR2 or CXCR4. MIF competed with cognate ligands for CXCR4 and CXCR2 binding, and directly bound to CXCR2. CXCR2 and CD74 formed a receptor complex, and monocyte arrest elicited by MIF in inflamed or atherosclerotic arteries involved both CXCR2 and CD74. In vivo, Mif deficiency impaired monocyte adhesion to the arterial wall in atherosclerosis-prone mice, and MIF-induced leukocyte recruitment required Il8rb (which encodes Cxcr2). Blockade of Mif but not of canonical ligands of Cxcr2 or Cxcr4 in mice with advanced atherosclerosis led to plaque regression and reduced monocyte and T-cell content in plaques. By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis. Targeting MIF in individuals with manifest atherosclerosis can potentially be used to treat this condition.