This paper addresses the general and challenging Sports Timetabling Problem proposed during the International Timetabling Competition of 2021 (ITC2021). The problem is expressed in a flexible format ...which enables modeling a number of real-world constraints that often occur in Sports Timetabling. An integer programming (IP) formulation and a fix-and-optimize heuristic are proposed to address the problem. The fix-and-optimize approach uses the IP formulation to heuristically decompose the problem into sub-problems and efficiently search on very large neighborhoods. The diverse ITC2021 benchmark instances were used to evaluate the proposed methods. The formulation resulted in proven optimal solutions for two instances. However, it failed to produce feasible solutions for most instances. The proposed fix-and-optimize, which uses an automatic sub-problem size calibration strategy, resulted in feasible solutions for 37 out of the 45 ITC2021 instances. Among these solutions, four are the best known in the literature. The proposed approach participated in the ITC2021 and was one of the finalists.
Monolithic tin oxide aerogels synthesized using the epoxide technique were characterized with X-ray diffraction, diffusive reflectance spectroscopy, infrared spectroscopy, particle induced X-ray ...emission and photoluminescence. Our results indicate that the resulting aerogel is an electrical semi-insulator. This happens due to an incomplete chemical reaction that leaves chloride and hydroxide ions unreacted. These ions form complexes with oxygen vacancy sites producing electron trapping. Furthermore, ions of Cu, Zn and Fe were identified as naturally occurring impurities in the gel matrix, substituting Sn+4 ions.
•High surface area tin oxide aerogel was grown using the epoxide technique.•We study the electronic structure of the material using spectroscopy and photoluminescence.•The absence of electrical conductivity is a consequence of high electron trapping.•Ions of Cu, Fe and Zn were identified by PIXE as naturally occurring impurities.
Abstract
This study employed the Economic Theory (ET) to calculate the production costs and the Emergy Methodology (EM) to identify the contributions of nature and economy of lambs produced in an ...intensive system located in Cravinhos city, State of São Paulo. In addition, was employed Emergy Methodology (EM) to identify the contributions of nature and economy in the system. The adopted scheme of cost allocation followed the classification according to ET, under Variable Cost (VC), Operational Fixed Cost (FC), Opportunity Costs of land and capital (OC), and Total Cost (TC). The EM manages to quantify all the resources used in the system in Contributions from Nature (I) and Feedback from the economy (F). The I originate from the Sum of Renewable (R) and Non-renewable (N) local resources, while that F is composed of the Materials (M) and Services (S) from the economic system. We found that to produce 935 lambs per year the TC was US$ 96,021.08. VC represented 19.08% of TC, while 76.6% were represented by FC, and 4.3% by the IF. The cost produced per animal and kg of live weight was US$ 72.73 and US$ 1.82, respectively. On the other hand, the total energy flow (Y) required by the system was 3.05E+16 seJ/yr (Solar Joules per year) for produce (Ep) 1.68E+06J/yr (Joules per year). Y was represented in a 53.92% by I (7.98% for R, from the sun, rain, and wind; and 45.94% for N, from the soil loss and groundwater), and 46,08% by F (27.8% for M, from the feed, minerals, steel, fueled, etc. and 10.7% for S, from manpower, other services external, taxes, etc.). These results show that the studied system has a %Renewability (%R = R / Y) of 7.98%. Thus, we can conclude that the system depends on 92.02% of resources from non-renewable sources.
Aims/hypothesis
Diabetic nephropathy is a major diabetic complication, and diabetes is the leading cause of end-stage renal disease (ESRD). Family studies suggest a hereditary component for diabetic ...nephropathy. However, only a few genes have been associated with diabetic nephropathy or ESRD in diabetic patients. Our aim was to detect novel genetic variants associated with diabetic nephropathy and ESRD.
Methods
We exploited a novel algorithm, ‘Bag of Naive Bayes’, whose marker selection strategy is complementary to that of conventional genome-wide association models based on univariate association tests. The analysis was performed on a genome-wide association study of 3,464 patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study and subsequently replicated with 4,263 type 1 diabetes patients from the Steno Diabetes Centre, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK collection (UK–Republic of Ireland) and the Genetics of Kidneys in Diabetes US Study (GoKinD US).
Results
Five genetic loci (
WNT4/ZBTB40-
rs12137135,
RGMA/MCTP2-
rs17709344,
MAPRE1P2-
rs1670754,
SEMA6D/SLC24A5-
rs12917114 and
SIK1-
rs2838302) were associated with ESRD in the FinnDiane study. An association between ESRD and rs17709344, tagging the previously identified rs12437854 and located between the
RGMA
and
MCTP2
genes, was replicated in independent case–control cohorts. rs12917114 near
SEMA6D
was associated with ESRD in the replication cohorts under the genotypic model (
p
< 0.05), and rs12137135 upstream of
WNT4
was associated with ESRD in Steno.
Conclusions/interpretation
This study supports the previously identified findings on the
RGMA
/
MCTP2
region and suggests novel susceptibility loci for ESRD. This highlights the importance of applying complementary statistical methods to detect novel genetic variants in diabetic nephropathy and, in general, in complex diseases.
Measuring insulin sensitivity in the presence of physiological changes in glucose and insulin concentrations, e.g., during a meal or OGTT, is important to better understand insulin resistance in a ...variety of metabolic conditions. Recently, two oral minimal models have been proposed to measure overall insulin sensitivity (S(I)) and its selective effect on glucose disposal (S(I)*) from oral tests. S(I) and S(I)* have been successfully validated against multiple tracer meal estimates, but validation against euglycemic hyperinsulinemic clamp estimates is lacking. Here, we do so in 21 subjects who underwent both a multiple-tracer OGTT and a labeled euglycemic hyperinsulinemic clamp. Correlation between minimal-model S(I), S(I) and corresponding clamp estimates S(I)(*clamp), S(I)(*clamp) was satisfactory, respectively r = 0.81, P < 0.001, and r = 0.71, P < 0.001. S(I) was significantly lower than S(I)(clamp) (8.08 +/- 0.89 vs. 13.66 +/- 1.69 10(-4) dl.kg(-1).min(-1) per microU/ml, P = 0.0002), whereas S(I) and S(I)(*clamp) were very similar (8.17 +/- 1.59 vs. 8.84 +/- 1.39 10(-4) dl.kg(-1).min(-1) per microU/ml, P = 0.52). These results add credibility to the oral minimal-model method as a simple and reliable physiological tool to estimate S(I) and S(I)*, also in large-scale clinical trials.
Background
Epidemiological data suggest that chronic hepatitis C virus (HCV) infection may contribute to the development of diabetes mellitus. Therapy of HCV infection with recombinant interferon‐α ...(r‐IFN‐α) can also impair of glucose metabolism.
Methods
To investigate the impact of HCV infection and the therapy with r‐IFN‐α on glucose metabolism we measured insulin sensitivity, glucose effectiveness, and first and second phase insulin secretion, using the minimal modelling analysis of frequently sampled intravenous glucose tolerance tests in 13 nondiabetic patients with HCV‐induced liver disease before and after therapy with r‐INF‐α (6 × 106 U, subcutaneously, three times a week over 4 months). Liver biopsy was performed to evaluate and score liver fibrosis as a marker of HCV‐induced cell injury.
Results
Insulin sensitivity (r = − 0.59, P < 0.05) and first phase insulin secretion (r = − 0.66, P < 0.03) were negatively related to the fibrosis score. Insulin sensitivity rose from 1.96 (SEM 0.37, n = 8) to 5.69 (SEM 0.99, n = 8) 10−4 min−1 per μU mL−1 (P < 0.01) in responders and from 2.51 (SEM 0.61, n = 5) to 6.95 (SEM 1.99, n = 5) in nonresponders after 4 months r‐INF‐α therapy. Fasting free fatty acids decreased significantly to about 50% (P < 0.01) in patients with and without therapy response after 4 months, whereas first phase insulin secretion did not change.
Conclusions
HCV‐induced liver injury is related to the deterioration of insulin sensitivity and first phase insulin response, thus impairing glucose homeostasis in these HCV‐infected patients. The administration of r‐INF‐α three times a week over 4 months is not associated with an impairment of glucose homeostasis.
The use of isotopic tracer studies to quantitate parameters characterizing apolipoprotein metabolism is enjoying a resurgence. This is due in large part to the availability of a number of stable ...isotopes and methods to measure them accurately in small quantities. Most experimental protocols in which stable isotopes are used call for endogenous labeling of the apolipoprotein of interest by an infusion of a labeled amino acid. Unlike the radioactively labeled amino acid counterpart in which turnover studies have traditionally been carried out for 72 hours to 14 days, the duration of the stable isotope experiment is normally less than 24 hours. This has contributed to some problems related to estimating the kinetic parameters because simplistic formulas whose underlying assumptions are not applicable to the lipoprotein system under study are often invoked. This is particularly true for the fractional synthetic rate (FSR). The purpose of this review is to address some of these problems. We derive the formula commonly used to estimate the FSR. In so doing, the underlying assumptions are carefully delineated. We then discuss several ways in which the formula is applied. Finally, we discuss the implications of these assumptions when the formula is applied to specific lipoprotein systems.
To investigate the link between hepatitis C infection and glucose intolerance, we measured insulin sensitivity, glucose effectiveness and beta-cell secretion in noncirrhotic HCV-infected patients ...with normal glucose tolerance according to WHO criteria as assessed by oral glucose tolerance tests.
Glucose, insulin and C-peptide data from frequently sampled intravenous glucose tolerance tests were analyzed using the minimal modeling technique for glucose and C-peptide to determine insulin sensitivity, glucose effectiveness, first and second phase insulin secretion in noncirrhotic HCV-infected patients (n = 10) and in healthy control subjects (n = 10). Histological activity index (HAI) as well as the extent of fibrosis were evaluated by scoring liver biopsies.
Insulin sensitivity (2.72 +/- 1.63 vs. 6.84 +/- 1. 20 10(-4) min(-1) per microU/ml, p < 0.01) and glucose effectiveness (2.29 +/- 0.45 vs. 2.89 +/- 0.39 10(-2) min(-1), p < 0.05) ere significantly lower in patients with HCV-induced liver disease. Insulin sensitivity was negatively related to serum alanine aminotransferase (r = -0.47, p < 0.05) and aspartate aminotransferase concentrations (r = -0.65, p < 0.05). Multiple linear regression analysis revealed a strong relation of insulin sensitivity with fibrosis score and HAI (r = -0.82, p < 0.02 for both). Second phase insulin secretion was significantly enhanced in HCV-infected patients (14.30 +/- 2.04 vs. 8.29 +/- 1.65 min(-1), p < 0.05).
HCV-infected patients with normal glucose tolerance are insulin and glucose resistant. The impairment of glucose tolerance appears to be closely related with the severity of HCV-induced liver damage.
We investigated the factors regulating glucose homeostasis in 10 healthy (control) subjects, as well as in stable, long-term, liver-grafted patients receiving monotherapy in the form of either ...cyclosporin A (n=10) or tacrolimus (n=10).
We measured insulin sensitivity, first- and second-phase insulin secretion, with a minimal modeling technique based on the analysis of glucose, insulin, and C-peptide profiles during frequently sampled intravenous glucose tolerance tests (FSIGTT). Proinsulin levels, as a marker of beta-cell dysfunction, were measured in the fasting state and during FSIGTT.
Glucose and insulin concentrations before and after glucose loading did not differ in liver transplant patients and in control subjects. Fasting C-peptide levels in both liver-grafted groups were higher than in healthy subjects and remained elevated during FSIGTT (P<0.05). Intravenous glucose tolerance (K(G)), i.e. the slope of the regression of logarithm of the blood glucose concentrations vs. time, insulin sensitivity, and first-phase insulin secretion did not differ in liver-grafted groups and healthy subjects. Second-phase insulin secretion was about 56% higher in liver-grafted patients than in controls (P<0.05). Body mass index was the overall determinant of insulin sensitivity in all groups.
Long-term monotherapy with cyclosporin A or tacrolimus has no deleterious effects on insulin sensitivity, first-phase insulin secretion, and insulin synthesis in liver transplant patients. Normal insulin sensitivity (posthepatic insulin effect) and enhanced second-phase insulin secretion (prehepatic insulin) point to an accelerated hepatic insulin clearance rate in liver transplant patients. Increased hepatic insulin clearance is compensated by enhanced insulin secretion, indicating that insulin clearance is the major determinant of pancreatic function in liver-grafted patients.
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