Heuristic Solutions for a Class of Stochastic Uncapacitated p-Hub Median Problems

2019 ◽  
Vol 53 (4) ◽  
pp. 1126-1149 ◽  
Author(s):  
Juanjo Peiró ◽  
Ángel Corberán ◽  
Rafael Martí ◽  
Francisco Saldanha-da-Gama
Keyword(s):  
Data Sets ◽  
Heuristic Procedure ◽  
Median Problem ◽  
Stochastic Version ◽  
Deterministic Equivalent ◽  
Starting Point ◽  
Compact Formulation ◽  
Finite Set ◽  
Shipping Traffic

In this work, we propose a heuristic procedure for a stochastic version of the uncapacitated r-allocation p-hub median problem with nonstop services. In particular, we assume that the number of hubs to which a terminal can be allocated is bounded from above by r. Additionally, we consider the possibility of shipping traffic directly between terminals (nonstop services). Uncertainty is associated with the traffic to be shipped between nodes and with the transportation costs. If we assume that such uncertainty can be captured by a finite set of scenarios, each of which with a probability known in advance, it is possible to develop a compact formulation for the deterministic equivalent problem. However, even for small instances of the problem, the model becomes too large to be tackled by a general solver. This fact motivates the development of a heuristic procedure, whose starting point is the determination of a feasible solution to every (deterministic) single-scenario problem. These solutions are then embedded into a process based on the path relinking methodology: gradually an initial solution to the overall problem is transformed by the incorporation of attributes from some guiding solutions. In our case, the guiding solutions are those found for the single-scenario problems. We report and discuss the results of the numerical experiments performed using instances randomly generated for the new problem from the well-known CAB and AP data sets.

scholarly journals Structure Elucidation of Urinary Metabolites of Fentanyl and Five Fentanyl Analogs using LC-QTOF-MS, Hepatocyte Incubations and Synthesized Reference Standards

2020 ◽  
Author(s):  
Jakob Wallgren ◽  
Svante Vikingsson ◽  
Tobias Rautio ◽  
Enas Nasr ◽  
Anna Åstrand ◽  
...  
Keyword(s):  
Urinary Metabolites ◽  
Reference Standards ◽  
Urine Samples ◽  
Data Sets ◽  
Hydroxylated Metabolites ◽  
Flight Mass Spectrometry ◽  
Starting Point ◽  
Fentanyl Analogs ◽  
Hydroxylated Metabolite

Abstract Fentanyl analogs constitute a particularly dangerous group of new psychoactive compounds responsible for many deaths around the world. Little is known about their metabolism, and studies utilizing liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analysis of hepatocyte incubations and/or authentic urine samples do not allow for determination of the exact metabolite structures, especially when it comes to hydroxylated metabolites. In this study, seven motifs (2-, 3-, 4- and β-OH as well as 3,4-diOH, 4-OH-3-OMe and 3-OH-4-OMe) of fentanyl and five fentanyl analogs, acetylfentanyl, acrylfentanyl, cyclopropylfentanyl, isobutyrylfentanyl and 4F-isobutyrylfentanyl were synthesized. The reference standards were analyzed by LC-QTOF-MS, which enabled identification of the major metabolites formed in hepatocyte incubations of the studied fentanyls. By comparison with our previous data sets, major urinary metabolites could tentatively be identified. For all analogs, β-OH, 4-OH and 4-OH-3-OMe were identified after hepatocyte incubation. β-OH was the major hydroxylated metabolite for all studied fentanyls, except for acetylfentanyl where 4-OH was more abundant. However, the ratio 4-OH/β-OH was higher in urine samples than in hepatocyte incubations for all studied fentanyls. Also, 3-OH-4-OMe was not detected in any hepatocyte samples, indicating a clear preference for the 4-OH-3-OMe, which was also found to be more abundant in urine compared to hepatocytes. The patterns appear to be consistent across all studied fentanyls and could serve as a starting point in the development of methods and synthesis of reference standards of novel fentanyl analogs where nothing is known about the metabolism.

Direct phase determination in electron crystallography: small organic molecules

1992 ◽  
Vol 50 (2) ◽  
pp. 1166-1167
Author(s):  
Douglas L. Dorset
Keyword(s):  
Organic Molecules ◽  
Data Sets ◽  
Temperature Structure ◽  
3D Analysis ◽  
Intensity Data ◽  
Electron Crystallography ◽  
Phase Determination ◽  
Measured Intensity ◽  
3D Data

The quantitative use of electron diffraction intensity data for the determination of crystal structures represents the pioneering achievement in the electron crystallography of organic molecules, an effort largely begun by B. K. Vainshtein and his co-workers. However, despite numerous representative structure analyses yielding results consistent with X-ray determination, this entire effort was viewed with considerable mistrust by many crystallographers. This was no doubt due to the rather high crystallographic R-factors reported for some structures and, more importantly, the failure to convince many skeptics that the measured intensity data were adequate for ab initio structure determinations.We have recently demonstrated the utility of these data sets for structure analyses by direct phase determination based on the probabilistic estimate of three- and four-phase structure invariant sums. Examples include the structure of diketopiperazine using Vainshtein's 3D data, a similar 3D analysis of the room temperature structure of thiourea, and a zonal determination of the urea structure, the latter also based on data collected by the Moscow group.

Identification of N-Substituted Triazolo-azetidines as Novel Antibacterials using pDualrep2 HTS Platform

2019 ◽  
Vol 22 (5) ◽  
pp. 346-354
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Large Scale ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
Reporter System ◽  
E Coli ◽  
Starting Point ◽  
High Concentrations ◽  
Mic Value

Aim and Objective: Antibiotic resistance is a serious constraint to the development of new effective antibacterials. Therefore, the discovery of the new antibacterials remains one of the main challenges in modern medicinal chemistry. This study was undertaken to identify novel molecules with antibacterial activity. Materials and Methods: Using our unique double-reporter system, in-house large-scale HTS campaign was conducted for the identification of antibacterial potency of small-molecule compounds. The construction allows us to visually assess the underlying mechanism of action. After the initial HTS and rescreen procedure, luciferase assay, C14-test, determination of MIC value and PrestoBlue test were carried out. Results: HTS rounds and rescreen campaign have revealed the antibacterial activity of a series of Nsubstituted triazolo-azetidines and their isosteric derivatives that has not been reported previously. Primary hit-molecule demonstrated a MIC value of 12.5 µg/mL against E. coli Δ tolC with signs of translation blockage and no SOS-response. Translation inhibition (26%, luciferase assay) was achieved at high concentrations up to 160 µg/mL, while no activity was found using C14-test. The compound did not demonstrate cytotoxicity in the PrestoBlue assay against a panel of eukaryotic cells. Within a series of direct structural analogues bearing the same or bioisosteric scaffold, compound 2 was found to have an improved antibacterial potency (MIC=6.25 µg/mL) close to Erythromycin (MIC=2.5-5 µg/mL) against the same strain. In contrast to the parent hit, this compound was more active and selective, and provided a robust IP position. Conclusion: N-substituted triazolo-azetidine scaffold may be used as a versatile starting point for the development of novel active and selective antibacterial compounds.

scholarly journals Constraints on neutrino non-standard interactions from LHC data with large missing transverse momentum

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
DianYu Liu ◽  
ChuanLe Sun ◽  
Jun Gao
Keyword(s):  
Transverse Momentum ◽  
Neutral Current ◽  
Data Sets ◽  
Leading Order ◽  
Missing Transverse Momentum ◽  
Upper Limit ◽  
Theoretical Predictions ◽  
Parton Showering ◽  
Single Jet

Abstract The possible non-standard interactions (NSIs) of neutrinos with matter plays important role in the global determination of neutrino properties. In our study we select various data sets from LHC measurements at 13 TeV with integrated luminosities of 35 ∼ 139 fb−1, including production of a single jet, photon, W/Z boson, or charged lepton accompanied with large missing transverse momentum. We derive constraints on neutral-current NSIs with quarks imposed by different data sets in a framework of either effective operators or simplified Z′ models. We use theoretical predictions of productions induced by NSIs at next-to-leading order in QCD matched with parton showering which stabilize the theory predictions and result in more robust constraints. In a simplified Z′ model we obtain a 95% CLs upper limit on the conventional NSI strength ϵ of 0.042 and 0.0028 for a Z′ mass of 0.2 and 2 TeV respectively. We also discuss possible improvements from future runs of LHC with higher luminosities.

Archiving of Food Samples from Restaurants and Caterers—Quantitative Profiling of Outbreaks of Foodborne Salmonellosis in Japan

2004 ◽  
Vol 67 (9) ◽  
pp. 2024-2032 ◽  
Author(s):  
FUMIKO KASUGA ◽  
MASAMITSU HIROTA ◽  
MASAMICHI WADA ◽  
TOSHIHIKO YUNOKAWA ◽  
HAJIME TOYOFUKU ◽  
...  
Keyword(s):  
Dose Response ◽  
Storage System ◽  
Epidemiological Data ◽  
Food Samples ◽  
Food Storage ◽  
Disease Rate ◽  
Data Sets ◽  
Response Data ◽  
Quantitative Profiling

The Ministry of Health, Labor and Welfare (former MHW) of Japan issued a Directive in 1997 advising restaurants and caterers to freeze portions of both raw food and cooked dishes for at least 2 weeks. This system has been useful for determining vehicle foods at outbreaks. Enumeration of bacteria in samples of stored food provide data about pathogen concentrations in the implicated food. Data on Salmonella concentrations in vehicle foods associated with salmonellosis outbreaks were collected in Japan between 1989 and 1998. The 39 outbreaks that occurred during this period were categorized by the settings where the outbreaks took place, and epidemiological data from each outbreak were summarized. Characteristics of outbreak groups were analyzed and compared. The effect of new food-storage system on determination of bacterial concentration was evaluated. Freezing and nonfreezing conditions prior to microbial examination were compared in the dose-response relationship. Data from outbreaks in which implicated foods had been kept frozen suggested apparent correlation between the Salmonella dose ingested and the disease rate. Combined with results of epidemiological investigation, quantitative data from the ingested pathogen could provide complete dose-response data sets.

A Reliability-Based Approach to Assess Fatigue Behaviour Based on Small Incomplete Data Sets

2008 ◽  
Vol 44-46 ◽  
pp. 871-878 ◽  
Author(s):  
Chu Yang Luo ◽  
Jun Jiang Xiong ◽  
R.A. Shenoi
Keyword(s):  
Incomplete Data ◽  
Standard Procedure ◽  
Fatigue Behaviour ◽  
Fatigue Tests ◽  
Small Sample ◽  
Data Sets ◽  
Safe Life ◽  
A New Technique ◽  
And Performance

This paper outlines a new technique to address the paucity of data in determining fatigue life and performance based on reliability concepts. Two new randomized models are presented for estimating the safe life and pS-N curve, by using the standard procedure for statistical analysis and dealing with small sample numbers of incomplete data. The confidence level formulations for the safe and p-S-N curve are also given. The concepts are then applied for the determination of the safe life and p-S-N curve. Two sets of fatigue tests for the safe life and p-S-N curve are conducted to validate the presented method, demonstrating the practical use of the proposed technique.

scholarly journals LOWER BOUNDS OF CHARACTERISTIC SCALE OF TOPOLOGICAL MODIFICATION OF THE NEWTONIAN GRAVITATION

2012 ◽  
Vol 21 (05) ◽  
pp. 1250048
Author(s):  
L. IORIO
Keyword(s):  
Semimajor Axis ◽  
Data Sets ◽  
Orbital Elements ◽  
Dynamical Models ◽  
Spatial Direction ◽  
Newtonian Gravitation ◽  
Complementary Approach ◽  
Local Modification

We analytically work out the long-term orbital perturbations induced by the leading order of perturbing potential arising from the local modification of the Newton's inverse square law due to a topology ℝ2 × 𝕊1 with a compactified dimension of radius R recently proposed by Floratos and Leontaris. We neither restrict to any specific spatial direction [Formula: see text] for the asymmetry axis nor to particular orbital configurations of the test particle. Thus, our results are quite general. Nonvanishing long-term variations occur for all the usual osculating Keplerian orbital elements, apart from the semimajor axis which is left unaffected. By using recent improvements in the determination of the orbital motion of Saturn from Cassini data, we preliminarily inferred R ≳ 4-6 kau . As a complementary approach, the putative topological effects should be explicitly modeled and solved-for with a modified version of the ephemerides dynamical models with which the same data sets should be reprocessed.

Theoretical determination of the structures of CaSiO3 perovskites

2006 ◽  
Vol 62 (6) ◽  
pp. 1025-1030 ◽  
Author(s):  
Razvan Caracas ◽  
Renata M. Wentzcovitch
Keyword(s):  
Crystal Structure ◽  
Experimental Data ◽  
Density Functional Theory ◽  
Density Functional ◽  
Theoretical Determination ◽  
Functional Theory ◽  
Starting Point ◽  
Atomic Coordinates ◽  
The Ideal

Density functional theory is used to determine the possible crystal structure of the CaSiO3 perovskites and their evolution under pressure. The ideal cubic perovskite is considered as a starting point for studying several possible lower-symmetry distorted structures. The theoretical lattice parameters and the atomic coordinates for all the structures are determined, and the results are discussed with respect to experimental data.

scholarly journals The seven sisters DANCe

2018 ◽  
Vol 612 ◽  
pp. A70 ◽  
Author(s):  
J. Olivares ◽  
E. Moraux ◽  
L. M. Sarro ◽  
H. Bouy ◽  
A. Berihuete ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Model Comparison ◽  
Precise Determination ◽  
Model Parameters ◽  
Data Sets ◽  
Adequate Model ◽  
Comparison Results ◽  
Bayesian Evidence ◽  
Mass Segregation

Context. Membership analyses of the DANCe and Tycho + DANCe data sets provide the largest and least contaminated sample of Pleiades candidate members to date. Aims. We aim at reassessing the different proposals for the number surface density of the Pleiades in the light of the new and most complete list of candidate members, and inferring the parameters of the most adequate model. Methods. We compute the Bayesian evidence and Bayes Factors for variations of the classical radial models. These include elliptical symmetry, and luminosity segregation. As a by-product of the model comparison, we obtain posterior distributions for each set of model parameters. Results. We find that the model comparison results depend on the spatial extent of the region used for the analysis. For a circle of 11.5 parsecs around the cluster centre (the most homogeneous and complete region), we find no compelling reason to abandon King’s model, although the Generalised King model introduced here has slightly better fitting properties. Furthermore, we find strong evidence against radially symmetric models when compared to the elliptic extensions. Finally, we find that including mass segregation in the form of luminosity segregation in the J band is strongly supported in all our models. Conclusions. We have put the question of the projected spatial distribution of the Pleiades cluster on a solid probabilistic framework, and inferred its properties using the most exhaustive and least contaminated list of Pleiades candidate members available to date. Our results suggest however that this sample may still lack about 20% of the expected number of cluster members. Therefore, this study should be revised when the completeness and homogeneity of the data can be extended beyond the 11.5 parsecs limit. Such a study will allow for more precise determination of the Pleiades spatial distribution, its tidal radius, ellipticity, number of objects and total mass.

scholarly journals Structure of human dual-specificity phosphatase 7, a potential cancer drug target

2015 ◽  
Vol 71 (6) ◽  
pp. 650-656 ◽  
Author(s):  
George T. Lountos ◽  
Brian P. Austin ◽  
Joseph E. Tropea ◽  
David S. Waugh
Keyword(s):  
Catalytic Domain ◽  
Three Dimensional ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Drug ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Starting Point ◽  
Mitogen Activated Protein ◽  
Dual Specificity Phosphatases

Human dual-specificity phosphatase 7 (DUSP7/Pyst2) is a 320-residue protein that belongs to the mitogen-activated protein kinase phosphatase (MKP) subfamily of dual-specificity phosphatases. Although its precise biological function is still not fully understood, previous reports have demonstrated that DUSP7 is overexpressed in myeloid leukemia and other malignancies. Therefore, there is interest in developing DUSP7 inhibitors as potential therapeutic agents, especially for cancer. Here, the purification, crystallization and structure determination of the catalytic domain of DUSP7 (Ser141–Ser289/C232S) at 1.67 Å resolution are reported. The structure described here provides a starting point for structure-assisted inhibitor-design efforts and adds to the growing knowledge base of three-dimensional structures of the dual-specificity phosphatase family.

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