Miracle-dz/UniFAR-FTUs huggingface dataset:
Iterative Improvement Methods for Knowledge-Based Scheduling

For large industrial applications the constraint-based formulation of scheduling problems fits better than mathematical representations from Operational Research, because the constraint approach is more flexible and can be adapted more easily to organizational changes in the production. However, the search for a good solution for realistic applications can be very expensive and furthermore, in scheduling one is not only interested in a feasible solution but also in an optimized solution.In this paper I present iterative improvement methods that can be used to optimize a schedule that is represented by constraints. These methods start with any schedule and try to optimize it by iterative modifications. The goal of the optimization method may be a minimization of the number of constraint violations or a maximization of a function that aggregates the satisfaction degrees of all involved soft constraints. Additionally, consistency techniques for constraints can be used to check a schedule after each modification. These problem solving methods have several benefits for realistic industrial applications. Since they can start with any preliminary schedule and can be interrupted anytime, they can be applied easily to reactive and cooperative scheduling. Further, they produce often better solutions in less time than other methods as was shown in several experiments.The paper gives an overview on important design decisions for iterative improvement methods, presents some of these methods in more detail and shows some results of our experiments made in applications of the steel-making industry.
Differences in cellular responses to mitogens in arterial smooth muscle cells derived from patients with moyamoya disease.

BACKGROUND AND PURPOSE Moyamoya disease is a progressive cerebrovascular occlusive disease affecting primarily children. The etiology remains unknown. We examined the chemotactic and proliferative activities of inflammatory cell products from arterial smooth muscle cells (SMCs) derived from moyamoya patients and compared them with those from control subjects. METHODS We used 12 SMC strains from moyamoya patients and eight from control subjects. SMC migration was examined in a micro chemotaxis chamber. DNA synthesis was measured by an immunoperoxidase technique. RESULTS Platelet-derived growth factor (PDGF)-BB markedly stimulated cell migration and DNA synthesis in control SMCs. PDGF-AA stimulated only DNA synthesis in control SMCs. In moyamoya SMCs, PDGF-AA and PDGF-BB stimulated cell migration but not DNA synthesis. Basic fibroblast growth factor had little migratory activity but stimulated DNA synthesis in moyamoya SMCs and control SMCs. Conversely, hepatocyte growth factor stimulated cell migration but not DNA synthesis in moyamoya SMCs and control SMCs. In contrast, interleukin-1 beta (IL-1 beta) significantly stimulated the migration and DNA synthesis of control SMCs, while it inhibited moyamoya SMC migration. The levels of IL-1 beta-induced nitric oxide production did not differ between moyamoya SMCs and control SMCs, suggesting that IL-1 beta inhibits the migration of moyamoya SMCs through a nitric oxide-independent pathway. CONCLUSIONS The differences in responses to PDGF and IL-1 in moyamoya SMCs are involved in the mechanism by which intimal thickening develops in moyamoya disease.
The Effectiveness of Foreign Exchange Intervention in Emerging Market Countries: Evidence from the Czech Koruna

We survey the literature on the efficacy of foreign exchange market intervention in emerging market countries, emphasising the differences with the literature on industrial countries. We then use official statistics on central bank intervention by the Czech National Bank in conjunction with options market data, to study the impact of intervention during 2001-02. We find that central bank intervention had some (weakly) statistically significant impact on the spot rate and the risk reversal but that this impact was small. We do not find evidence that intervention had an influence on short-term exchange rate volatility. We also find that, in our sample period, Czech authorities appeared to intervene mainly in response to an acceleration of the speed of koruna appreciation.
Comprehensive tumor profiling identifies numerous biomarkers of drug response in cancers of unknown primary site: Analysis of 1806 cases

Background Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Despite extensive laboratory and imaging efforts, the primary site usually cannot be unequivocally confirmed, and the treatment for the most part remains empirical. Recently, identification of common cancer pathway alterations in diverse cancer lineages has offered an opportunity to provide targeted therapies for patients with CUP, irrespective of the primary site. Patients and Methods 1806 cancers of unknown primary were identified among more than 63,000 cases profiled at Caris Life Sciences. Multiplatform profiling of the tumor samples included immunohistochemistry, gene sequencing and in situ hybridization methods in an effort to identify changes in biomarkers that are predictive of drug responses. Results Biomarkers associated with a potential drug benefit were identified in 96% of cases. Biomarkers identified included those associated with potential benefit in nearly all classes of approved cancer drugs (cytotoxic, hormonal, targeted biological drugs). Additionally, biomarkers associated with a potential lack of benefit were identified in numerous cases, which could further refine the management of patients with CUP. Conclusion Comprehensive biomarker profiling of CUP may provide additional choices in treatment of patients with these difficult to treat malignancies.
ALLUVIAL CHANNEL GEOMETRY : THEORY AND ApPLICATIONS

The discusser would like to congratulate the authors for their interesting approach to the generalized regime formulas. The purpose of this discussion is (1) to generalize the authors' findings; and (2) to give an explicit approach for the flow depth h. Eqs. (28)-(31) are used as the basis of this discussion. The common denominator of all exponents is 'Y = 5 + 6m, and one may show that It is necessary to add here that in the authors' example, the numbers for the width and the average velocity are wrong. The correct equations should read W = 1.33Q(2+4m)/(H6m)d;4m/(H6m)S-(I+2m)l(H6m) (29)
Geographic distribution of autism in California: A retrospective birth cohort analysis

Prenatal environmental exposures are among the risk factors being explored for associations with autism. We applied a new procedure combining multiple scan cluster detection tests to identify geographically defined areas of increased autism incidence. This procedure can serve as a first hypothesis‐generating step aimed at localized environmental exposures, but would not be useful for assessing widely distributed exposures, such as household products, nor for exposures from nonpoint sources, such as traffic.
Representativeness of the dabigatran, apixaban and rivaroxaban clinical trial populations to real-world atrial fibrillation patients in the United Kingdom: a cross-sectional analysis using the General Practice Research Database

Objective Three oral anticoagulants have reported study results for stroke prevention in patients with atrial fibrillation (AF) (dabigatran etexilate, rivaroxaban and apixaban); all demonstrated superiority or non-inferiority compared with warfarin (RE-LY, ARISTOTLE and ROCKET-AF). This study aimed to assess the representativeness for the real-world AF population, particularly the population eligible for anticoagulants. Design A cross-sectional database analysis. Setting Dataset derived from the General Practice Research Database (GPRD). Primary and secondary outcomes measure The proportion of real-world patients with AF who met the inclusion/exclusion criteria for RE-LY, ARISTOTLE and ROCKET-AF were compared. The results were then stratified by risk of stroke using CHADS2 and CHA2DS2-VASc. Results 83 898 patients with AF were identified in the GPRD. For the population at intermediate or high risk of stroke and eligible for anticoagulant treatment (CHA2DS2-VASc ≥1; n=78 783 (94%)), the proportion eligible for inclusion into RE-LY (dabigatran etexilate) was 68% (95% CI 67.7% to 68.3%; n=53 640), compared with 65% (95% CI 64.7% to 65.3%; n=51 163) eligible for ARISTOTLE (apixaban) and 51% (95% CI 50.7% to 51.4%; n=39 892) eligible for ROCKET-AF (rivaroxaban). Using the CHADS2 method of risk stratification, for the population at intermediate or high risk of stroke and eligible for anticoagulation treatment (CHADS2 ≥1; n=71 493 (85%)), the proportion eligible for inclusion into RE-LY was 74% (95% CI 73.7% to 74.3%; n=52 783), compared with 72% (95% CI 71.7% to 72.3%; n=51 415) for ARISTOTLE and 56% (95% CI 55.6% to 56.4%; n=39 892) for ROCKET-AF. Conclusions Patients enrolled within RE-LY and ARISTOTLE were more reflective of the ‘real-world’ AF population in the UK, in contrast with patients enrolled within ROCKET-AF who were a more narrowly defined group of patients at higher risk of stroke. Differences between trials should be taken into account when considering the applicability of findings from randomised clinical trials. However, assessing representativeness is not a substitute for assessing generalisibility, that is, how well clinical trial results would translate into effectiveness and safety in everyday routine care.
Primary human breast adenocarcinoma: imaging and histologic correlates of intrinsic susceptibility-weighted MR imaging before and during chemotherapy.

PURPOSE To investigate the histopathologic and dynamic magnetic resonance (MR) imaging correlates of intrinsic susceptibility-weighted (ISW) MR imaging in patients with primary human breast adenocarcinoma and to assess the relationship between baseline transverse relaxation rate (R2*) and T2* relaxivity change (ΔR2*) and the response to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS Institutional ethics approval and informed consent were obtained. Between September 2001 and January 2008, 83 women (median age, 46 years; age range, 26-72 years) with breast cancer were recruited to undergo dynamic contrast medium-enhanced (DCE), dynamic susceptibility contrast-enhanced (DSC), and ISW MR imaging before and after two cycles of NAC. After excluding necrotic, infiltrating, and invasive lobular carcinomas, 31 patients were available for baseline assessment and 27 were available for response assessment. Transfer constant, leakage space, rate constant, initial area under the gadolinium concentration-time curve at 60 seconds, relative blood volume (rBV), relative blood flow (rBF), and R2* were calculated. Relationships between baseline R2* and histopathologic variables (tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor 2 status), tumor size, and dynamic MR imaging parameters were sought. Baseline adenocarcinoma R2* (n = 31) and ΔR2* (n = 27) were correlated with final pathologic response. RESULTS Inverse correlations between baseline R2* and rBV (ρ = -0.48, P = .013) and rBF (ρ = -0.44, P = .024) were found, but not after NAC. No relationships were observed between baseline R2* and other kinetic imaging parameters, histopathologic characteristics, or tumor size (P > .05). Baseline R2* values were lower in tumors than in normal breast tissue (31.8 sec(-1) vs 36.2 sec(-1), P = . 017) but not after NAC. Increases in R2* were observed after treatment (31.1 sec(-1) vs 34.8 sec(-1), P = . 006), with larger increases correlating with pathologic response. ΔR2* was not as effective as DCE or DSC MR imaging parameters in the prediction of response. CONCLUSION R2* is influenced by blood volume in untreated breast adenocarcinomas. Increases in R2* after two cycles of NAC correlate with pathologic response. Therapy-induced uncoupling of the relationship between R2* and rBV and rBF is consistent with responding tumors becoming hypoxic early during treatment. SUPPLEMENTAL MATERIAL http://radiology.rsna. org/lookup/suppl/doi:10.1148/radiol.10100421/-/DC1.
Routing and Staffing in Large-Scale Service Systems: The Case of Homogeneous Impatient Customers and Heterogeneous Servers

Motivated by call centers, we study large-scale service systems with homogeneous impatient customers and heterogeneous servers; the servers differ with respect to their speed of service. For this model, we propose staffing and routing rules that are jointly asymptotically optimal in the heavy-traffic many-server QED, ED, and ED + QED regimes, respectively. For the QED regime, our proposed routing rule is FSF, that assigns customers to the fastest server available first. In the ED and ED + QED regimes, all work-conserving policies perform (asymptotically) equally well. In all these regimes, the form of the asymptotically optimal staffing is consistent with the asymptotically optimal staffing in the same regimes in the single-pool case, respectively. In particular, the total service capacity is (asymptotically) equal to a term that is proportional to the arrival rate plus, possibly, a term that is proportional to the square-root of the arrival rate, with both terms being regime dependent. Our specific proposed approximation for the optimal staffing vector is obtained via a straightforward solution to a deterministic optimization problem subject to a linear feasible region.
Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients

S-CKD602 is a PEGylated liposomal formulation of CKD-602, a potent topoisomerase I inhibitor. The objective of this study was to characterize the bidirectional pharmacokinetic–pharmacodynamic (PK–PD) interaction between S-CKD602 and monocytes. Plasma concentrations of encapsulated CKD-602 and monocytes counts from 45 patients with solid tumors were collected following intravenous administration of S-CKD602 in the phase I study. The PK–PD models were developed and fit simultaneously to the PK–PD data, using NONMEM®. The monocytopenia after administration of S-CKD602 was described by direct toxicity to monocytes in a mechanism-based model, and by direct toxicity to progenitor cells in bone marrow in a myelosuppression-based model. The nonlinear PK disposition of S-CKD602 was described by linear degradation and irreversible binding to monocytes in the mechanism-based model, and Michaelis–Menten kinetics in the myelosuppression-based model. The mechanism-based PK–PD model characterized the nonlinear PK disposition, and the bidirectional PK–PD interaction between S-CKD602 and monocytes.
Induced Pluripotent Stem Cells in Cardiovascular Drug Discovery

The unexpected discovery that somatic cells can be reprogrammed to a pluripotent state yielding induced pluripotent stem cells has made it possible to produce cardiovascular cells exhibiting inherited traits and disorders. Use of these cells in high throughput analyses should broaden our insight into fundamental disease mechanisms and provide many benefits for patients, including new therapeutics and individually tailored therapies. Here we review recent progress in generating induced pluripotent stem cell-based models of cardiovascular disease and their multiple applications in drug development.
Program transformation by templates based on term rewriting

Huet and Lang (1978) presented a framework of automated program transformation based on lambda calculus in which programs are transformed according to a given program transformation template. They introduced a second-order matching algorithm of simply-typed lambda calculus to verify whether the input program matches the template. They also showed how to validate the correctness of the program transformation using the denotational semantics.We propose in this paper a framework of program transformation by templates based on term rewriting. In our new framework, programs are given by term rewriting systems. To automate our program transformation, we introduce a term pattern matching problem and present a sound and complete algorithm that solves this problem.We also discuss how to validate the correctness of program transformation in our framework. We introduce a notion of developed templates and a simple method to construct such templates without explicit use of induction. We then show that in any program transformation by developed templates the correctness of the transformation can be verified automatically. In our framework the correctness of the program transformation is discussed based on the operational semantics. This is a sharp contrast to Huet and Lang's framework.
Algorithms for Inverse Pyramid Image Decomposition

A new class of algorithms for image decomposition, named Inverse P y amid Decomposition (IPD), is explored in this work. The algorithms of this class, developed and anal yzed in the present work, are based on image approximation in the pyramid levels with a set of models. The algorithm for pyramid decomposition, known as Reduced Difference P yramid (RDP) [2], which is the closest of the same class, is used as a base for comparison. The obtained results by the help of modeling reveal that the algorithm of the new class which uses a combination of oriented surfaces and plains achieves a much better efficiency than the RDP. Key-Words: Inverse Pyramid Decomposition, mean squared error approximation, oriented surface, oriented plain IMACS/IEEE CSCC'99 Proceedings, Pages:1961-1965
Lipid peroxidation status as an index to evaluate the influence of dietary fats on vitamin E requirements of young pigs

The aims of the present study were to establish a suitable criterion for estimating the vitamin E requirement for young pigs, and to investigate the influence of dietary fats on the requirement of this nutrient. In Expt 1 weaned pigs were given a semi-purified diet supplemented with 0,20, or 100 mg DL- α-tocopheryl acetate/kg. Pigs in Expt 2 were fed on diets containing 10 g sunflower oil (SO) stripped of vitamin E/kg in diets 1 and 2, 100 g SO/kg in diets 3 and 4, and 100 g tallow/kg in diet 5. Diets 2, 4 and 5 were supplemented with DL-α-tocopheryl acetate at 20 mg/kg for 0·28 d and 50 mg/kg for 29–56 d of the experiment respectively. Results showed that vitamin E concentrations in plasma and tissues reflected dietary levels of vitamin E. No apparent clinical signs of vitamin 'E deficiency were observed, but pigs fed on diets without vitamin E supplementation showed a higher (P < 0·05) lipid peroxidation status as indicated by thiobarbituric acid-reactive substances in erythrocytes, and ethane and pentane levels in exhaled gases than those fed on supplemental diets. This indicated that the former was deficient in vitamin E. Data in Expt 1 suggested that supplementation with 20 mg DL-α-tocopheryl acetate/kg is adequate for young pigs when the diet contains 30 g lard/kg. However, results in Expt 2 showed that this level was inadequate when the diet contains 100 g SO/kg or its equivalent to 70 mg polyunsaturated fatty acids (PUFA)/g. Vitamin E and lipid peroxidation status of pigs were affected by both dietary vitamin E and dietary PUFA. This demonstrates that the requirement for vitamin E in young pigs increases as PUFA levels in the diet increase. The present study shows that lipid peroxidation response of pigs is a suitable index to evaluate vitamin E requirements.
In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis.

PURPOSE The interaction between leukocytes and vascular endothelial cells plays an important role in various inflammatory disorders. This study evaluated leukocyte behavior in the retina during endotoxin-induced uveitis (EIU) in vivo. METHODS EIU was induced in female Lewis rats by footpad injection of lipopolysaccharide (LPS). The time-course changes of retinal leukocyte behavior were followed at 1.5, 3, 4.5, 6, 12, 24, 48, 72, and 120 hours after LPS treatment using acridine orange digital fluorography, consisting of high-resolution images from a scanning laser ophthalmoscope and a fluorescent nuclear dye of acridine orange. RESULTS Major retinal vessels were significantly dilated (P < 0.05) at 4.5 hours after LPS injection. The vasodilation, marked in veins, became maximum at 24 hours and subsided at 72 hours. Leukocytes were observed rolling along the walls of major veins at 4.5 hours. The number of rolling leukocytes gradually increased and reached a peak level of 33.8 +/- 3.4 cells/minute per major vein at 12 hours. Leukocyte rolling was still observed at 72 hours. No rolling of leukocytes was observed along the arterial walls throughout any experiments. The velocities of rolling leukocytes were determined at 6, 12, 24, and 48 hours. The leukocyte rolling velocity at 6 hours was significantly slower (33.3 +/- 2.8 microns/second, P < 0.05) than at the other three times (average, 46.6 microns/second). Cellular infiltration into the vitreous cavity was detected at 24 hours and reached its maximum at 48 hours. CONCLUSIONS This study demonstrates that it is possible to evaluate EIU by investigating retinal leukocyte behavior and that vasodilation of major retinal vessels and leukocyte-endothelial interactions precede inflammatory cell emigration into the vitreous. This method may be useful to quantify the severity of inflammation in EIU.