ABSTRACT
In this work we propose a modified Chord Length Sampling (CLS) algorithm, endowed with two layers of "memory effects," aimed at solving particle transport problems in one-dimensional spatially nonhomogeneous Markov media. CLS algorithms are a family of Monte Carlo methods which account for the stochastic nature of the media by sampling on-the-fly the random interfaces between material phases during the particle propagation. The possibility for the particles to remember the last crossed interfaces increases the accuracy of these models with respect to reference solutions obtained by solving the Boltzmann equation on a large number of realizations of the Markov media. In previous investigations, CLS models with memory have been tested exclusively for spatially uniform stochastic media: in this paper we extend this class of Monte Carlo methods to the case of spatially nonhomogeneous configurations. The effectiveness and the robustness of the modified CLS are probed considering several benchmark problems with varying material cross sections and Markov media densities. The obtained results are a stepping stone towards a generalization to three-dimensional models.
ABSTRACT
Modification of 5-aryl-4-trifluoroacetyltriazoles at the NH-moiety was investigated. Screening of the alkylation conditions revealed that using Na2CO3 as a base and DMF as a solvent of 2-substituted triazoles can be preferentially prepared in up to 86% yield. In the best cases, the amount of minor 1-alkyl isomer was less than 6%. SNAr reaction of the 5-aryl-4-trifluoroacetyltriazoles with aryl halides having electron-withdrawing groups led to regiospecific formation of 2-aryltriazoles isolated in good-to-high yields. Chan-Lam reaction of the 5-aryl-4-trifluoroacetyltriazoles with boronic acids afforded 2-aryltriazoles as single isomers in up to 89% yield. The subsequent reaction of the prepared 2-aryltriazoles with primary and secondary amines gave a set of amides of 4-(2,5-diaryltriazolyl)carboxylic acid. The fluorescent properties of the prepared 2-substituted derivatives of triazoles were investigated to demonstrate their utility as new efficient luminophores having more than 60% quantum yields.
ABSTRACT
OBJECTIVES: Transtubular potassium gradient has never been evaluated in the diagnosis of primary hypoadrenocorticism in dogs. The objective of this study is to evaluate the diagnostic utility of transtubular potassium gradient for the diagnosis of primary hypoadrenocorticism in dogs with serum K+ > 5.5 mol/L. MATERIALS AND METHODS: Cross-sectional study including dogs with primary hypoadrenocorticism and dogs with other disease. Differences in signalment and laboratory parameters between groups were assessed by binary logistic regression modelling. Variables significantly associated with primary hypoadrenocorticism were evaluated for their diagnostic accuracy of this condition by receiver operator characteristic curve analysis and by multivariable logistic regression analysis, respectively. RESULTS: Dogs with primary hypoadrenocorticism (n=39) were significantly younger than hyperkalemic dogs without primary hypoadrenocorticism (n=41). Moreover they had higher serum and urinary concentrations of Na+ and Na+ :K+ , but lower transtubular potassium gradient than hyperkalemic dogs without hypoadrenocorticism. Serum Na+ (sNa+ ) had the highest diagnostic accuracy (area under the curve [AUC]: 0.87, 95% confidence interval, 0.78 to 0.96), followed by the transtubular potassium gradient (AUC: 0.81, 0.72 to 0.91), however the accuracy of the two AUCs was not statistically different. The transtubular potassium gradient-sNa+ additive index (i.e. transtubular potassium gradient+sNa+ /10) had a greater accuracy (AUC: 0.88, 0.79 to 0.94) than transtubular potassium gradient or sNa+ , although it was not statistically superior to the latter. The multivariable logistic regression model showed that transtubular potassium gradient (adjusted odds ratio [aOR]: 0.51, 0.3 to 0.84), sNa+ (aOR: 0.86, 0.78 to 0.95) and spayed female (aOR: 24.96, 2.32 to 267.66) were associated with primary hypoadrenocorticism. CLINICAL SIGNIFICANCE: Transtubular potassium gradient-sNa+ additive index can contribute to decision-making on diagnosis of primary hypoadrenocorticism in dogs presenting with hyperkalaemia.
Subject(s)
Adrenal Insufficiency , Dog Diseases , Hyperkalemia , Dogs , Female , Animals , Hyperkalemia/diagnosis , Hyperkalemia/veterinary , Cross-Sectional Studies , Dog Diseases/diagnosis , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/veterinary , PotassiumABSTRACT
A detailed study of the reaction of CF3-ynones with NaN3 was performed. It was found that the reaction permits the selective synthesis of either 4-trifluoroacetyltriazoles or 5-CF3-isoxazoles. The chemoselectivity of the reaction was switchable via acid catalysis. The reaction of CF3-ynones with NaN3 in EtOH produced high yields of 4-trifluoroacetyltriazoles. In contrast, the formation of 5-CF3-isoxazoles was observed under catalysis by acids. This acid-switchable procedure can be performed at sub-gram scale. The possible reaction mechanism was supported by DFT calculations. The synthetic utility of the prepared 4-trifluoroacetyltriazoles was demonstrated.
Subject(s)
Isoxazoles , Triazoles , Catalysis , AcidsABSTRACT
Halogenation of 2-trifluoromethylindole afforded 3-chloro-, 3-bromo- and 3-iodo derivatives in up to 98% yield. Methyl-, benzyl- and tosyl-groups can be installed at the nitrogen atom of prepared indoles in high yields by base catalyzed reaction with the corresponding alkylating (sulfonylating) reagents. A high synthetic utility of the prepared haloindoles in the reaction with various nucleophilies was shown. The reaction with 4-methylthiophenol and copper cyanide afforded the corresponding sulfides and nitriles in high yield. Palladium catalyzed cross-coupling with phenyl boronic acid and phenylacetylene gave the corresponding 3-phenyl-2-CF3-indoles and acetylenic derivatives in 72-98% yield.
Subject(s)
Cyanides , Indoles , Catalysis , Nitriles , Halogenation , PalladiumABSTRACT
The catalytic olefination reaction of 2-nitrobenzaldehydes with CF3CCl3 afforded stereoselectively trifluoromethylated ortho-nitrostyrenes in up to 88% yield. The reaction of these alkenes with pyrrolidine permits preparation of α-CF3-ß-(2-nitroaryl) enamines. Subsequent one pot reduction of nitro-group by Fe-AcOH-H2O system initiated intramolecular cyclization to afford 2-CF3-indoles. Target products can be prepared in up to 85% yields. Broad synthetic scope of the reaction was shown as well as some followed up transformations of 2- CF3-indole.
ABSTRACT
The reaction of α-CF3-ß-(2-nitroaryl) enamines with benzaldehydes afforded effectively α,ß-diaryl-CF3-enones having nitro group. Subsequent reduction of nitro group by NH4HCO2-Pd/C system initiated intramolecular cyclization to give 2-CF3-3-benzylindoles. Target products can be prepared in up to quantitative yields. Broad synthetic scope of the reaction was shown. Probable mechanism of indole formation is proposed.
ABSTRACT
The reaction of α-CF3-ß-(2-nitroaryl)enamines with benzaldehydes led to nitro-substituted α,ß-diaryl-CF3-enones in high yield. Subsequent reduction of the nitro-group to the amino moiety by the Pd/C-NH4HCO2 system resulted in intramolecular cyclization to form a 5-membered hemiaminal which is stabilized by the presence of a CF3-group. The reaction of this hemiaminal with various nucleophiles afforded functionalized 2-CF3-indoles isolated in up to quantitative yields. High efficiency and broad synthetic scope of all steps of the sequence were demonstrated. A possible mechanism of the reaction is discussed.
ABSTRACT
α-CF3-enamines can be prepared by the reaction of pyrrolidine with the corresponding haloalkenes. The prepared enamines react with 2-nitrobenzaldehydes to give ortho-nitro-substituted α,ß-diaryl-CF3-enones highly stereoselectively in up to 88% yield. Subsequent reduction of the nitro-group by an Fe-AcOH system promotes intramolecular cyclization to afford 2-CF3-3-arylquinolines in up to 99% isolated yield. High synthetic utility of all synthetic steps of the sequence was shown. A one-pot procedure was developed to give the target trifluoromethylated quinolines directly from enamines or haloalkenes.
ABSTRACT
An efficient pathway toward a novel class of trifluoromethyl building blocks was elaborated. The reaction of α-CF3-enamines with arylaldehydes resulted in direct synthesis of α,ß-diaryl-CF3-enones isolated in up to 93% yield as E-isomers. The possible reaction mechanism was proposed using the Zimmerman-Traxler model. The reaction of α,ß-diaryl-CF3-enones with hydrazines opens a novel pathway to trifluoromethylated pyrazolines. Oxidation of pyrazolines with DDQ opened access to totally regioselective preparation of 3-CF3-pyrazoles isolated in high yield. Using this strategy, 4-arylated derivatives of known drugs Celebrex, Mavacoxib, and SC-560 can be synthesized.
Subject(s)
Hydrazines , Pyrazoles , Oxidation-ReductionABSTRACT
The reaction of pyridines with trifluoroacetylated acetylenes was investigated. It was found that the reaction of various pyridines with two molecules of CF3CO-acetylenes proceeds under mild metal-free conditions. As a result, efficient stereoselective synthesis of 3-arylethynyl-3-trifluoromethyl-1,3-oxazinopyridines was elaborated. Target heterocycles can be prepared in up to quantitative yields.
Subject(s)
Alkynes/chemistry , Heterocyclic Compounds/chemical synthesis , Pyridines/chemistry , Halogenation , Heterocyclic Compounds/chemistry , Molecular StructureABSTRACT
Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.
Subject(s)
Dog Diseases/diagnosis , Gallbladder Diseases/veterinary , Hyperbilirubinemia/veterinary , Mucocele/veterinary , Adrenocortical Hyperfunction/veterinary , Animals , Bilirubin/blood , Biomarkers , Dog Diseases/mortality , Dog Diseases/surgery , Dogs , Gallbladder Diseases/diagnosis , Gallbladder Diseases/mortality , Gallbladder Diseases/surgery , Genetic Predisposition to Disease , Hyperlipidemias/veterinary , Mucocele/diagnosis , Mucocele/mortality , Mucocele/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
In most cases, the underlying causes of feline pancreatitis and feline immune-mediated haemolytic anaemia (IMHA) remain unknown. Following the observation that some cats present with both diseases concurrently, the aim of this cross-sectional study was to investigate if the two disorders were associated statistically in this species. A residency case log of all cases seen at the Small Animal Hospital, University of Glasgow, Glasgow, UK, between July 2004 and December 2007, was used as the database for this study and an association between these two disorders was assessed by Fisher's exact test. Of the 155 sick cats included in the study, nine were diagnosed at the time of presentation with pancreatitis (prevalence of 5.8%) and 11 with IMHA (prevalence of 7.1%). In three of these cats both conditions were present concurrently at the time of presentation (prevalence of 1.9%). A significant association between these two disease was found (Odds Risk 8.63, exact 95% confidence interval 1.15-49.31, P = 0.0178). Two possible biological explanations for the statistical association found between these two diseases are that one of these conditions may represent the cause for the onset of the other or that an underlying disorder of the immune system may concurrently target feline red blood cells and the exocrine pancreas.
Subject(s)
Anemia, Hemolytic, Autoimmune/veterinary , Cat Diseases/epidemiology , Pancreatitis/veterinary , Animals , Cats , Cross-Sectional Studies , Female , Male , Pets , PrevalenceABSTRACT
BACKGROUND: Ascitic fluids of horses and humans have fibrinolytic activity, independent of the underlying mechanism of fluid formation. OBJECTIVE: To determine whether coagulation and fibrinogenolytic/fibrinolytic activity (ie, low fibrinogen and increased fibrin-fibrinogen degradation products [FDPs], D-dimer, or both) occur in all types of ascitic fluid in dogs. ANIMALS: A total of 70 client-owned dogs with ascites. METHODS: In this cross-sectional study, dogs were categorized based on the pathophysiology of fluid formation into 4 groups: transudates due to decreased osmotic pressure, transudates due to increased hydrostatic pressure, exudates, and hemorrhagic ascites. Fibrinogen, FDPs, and D-dimer concentrations were measured and then compared in both ascitic fluid and plasma. RESULTS: Ten dogs had transudates due to decreased colloid osmotic pressure, 18 had transudates due to increased hydrostatic pressure, 13 had exudates, and 29 had hemorrhagic ascites. Ascitic fibrinogen concentrations (n = 70) were significantly lower (median = 59 mg/dL; range: 59-122 mg/dL) than those in the plasma (median = 168 mg/dL, range: 59-879 mg/dL; P < .0001). Ascitic FDPs concentrations (n = 70) were significantly higher (<5 µg/mL: 3/70 dogs, ≥5 to <20 µg/mL: 11/70 dogs, ≥20 µg/mL: 56/70 dogs) than those in the plasma (<5 µg/mL: 17/70 dogs, ≥5 to <20 µg/mL: 28/70 dogs, ≥20 µg/mL: 25/70 dogs; P < .0001). Ascitic D-dimer concentrations (n = 70) were significantly higher (median = 3.98 µg/mL, range: 0.02-9.19) than those in the plasma (median = 0.11 µg/mL, range: 0.01-4.08; P < .0001). Analysis of the data for each of the 4 different types of ascites showed similar results to those of all the data analyzed together. CONCLUSIONS AND CLINICAL IMPORTANCE: Ascitic fluid of dogs has evidence of coagulation activation and fibrinogenolytic/fibrinolytic activity and that this phenomenon occurs independent of the underlying mechanism that leads to the formation of ascites.
Subject(s)
Ascites/veterinary , Ascitic Fluid/metabolism , Blood Coagulation Disorders/veterinary , Dog Diseases/metabolism , Animals , Ascites/metabolism , Blood Coagulation Disorders/metabolism , Cross-Sectional Studies , Dogs , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Male , Partial Thromboplastin TimeABSTRACT
Random tessellations of the space represent a class of prototype models of heterogeneous media, which are central in several applications in physics, engineering, and life sciences. In this work, we investigate the statistical properties of d-dimensional isotropic Poisson geometries by resorting to Monte Carlo simulation, with special emphasis on the case d=3. We first analyze the behavior of the key features of these stochastic geometries as a function of the dimension d and the linear size L of the domain. Then, we consider the case of Poisson binary mixtures, where the polyhedra are assigned two labels with complementary probabilities. For this latter class of random geometries, we numerically characterize the percolation threshold, the strength of the percolating cluster, and the average cluster size.
ABSTRACT
The neutron population in a nuclear reactor is subject to fluctuations in time and in space due to the competition of diffusion by scattering, births by fission events, and deaths by absorptions. As such, fission chains provide a prototype model for the study of spatial clustering phenomena. In order for the reactor to be operated in stationary conditions at the critical point, the population of prompt neutrons instantaneously emitted at fission must be in equilibrium with the much smaller population of delayed neutrons, emitted after a Poissonian time by nuclear decay of the fissioned nuclei. In this work, we will show that the delayed neutrons, although representing a tiny fraction of the total number of neutrons in the reactor, actually have a key impact on the fluctuations, and their contribution is very effective in quenching the spatial clustering.
ABSTRACT
We study the evolution of a collection of individuals subject to Brownian diffusion, reproduction, and disappearance. In particular, we focus on the case where the individuals are initially prepared at equilibrium within a confined geometry. Such systems are widespread in physics and biology and apply for instance to the study of neutron populations in nuclear reactors and the dynamics of bacterial colonies, only to name a few. The fluctuations affecting the number of individuals in space and time may lead to a strong patchiness, with particles clustered together. We show that the analysis of this peculiar behavior can be rather easily carried out by resorting to a backward formalism based on the Green's function, which allows the key physical observables, namely, the particle concentration and the pair correlation function, to be explicitly derived.
Subject(s)
Models, Theoretical , Motion , Computer Simulation , Diffusion , Monte Carlo MethodABSTRACT
OBJECTIVE: To investigate the iron status, its relationship with C-reactive protein and the prognostic value of both in canine leishmaniasis. METHOD: Eighty-six dogs with leishmaniasis and two control groups (healthy dogs and dogs with diseases other than leishmaniasis) were selected. Iron status indicators and C-reactive protein were compared between the three groups. Correlations between C-reactive protein and iron, ferritin and total iron-binding capacity were evaluated in dogs with leishmaniasis. Iron, total iron-binding capacity and ferritin were compared between dogs stratified according to similar C-reactive protein concentrations. The mortality rate at 30 days post-diagnosis was compared between groups. Iron status indicators and C-reactive protein were compared between survivors and non-survivors. RESULTS: Dogs with leishmaniasis had lower iron and total iron-binding capacity and higher ferritin and C-reactive protein. There was a significant but low correlation of C-reactive protein with iron, ferritin and total iron-binding capacity. Dogs with leishmaniasis had decreased iron and total iron-binding capacity and increased ferritin compared to other ill patients with similar C-reactive protein concentrations. Mortality was not significantly different between groups but non-survivor dogs with leishmaniasis had higher C-reactive protein and lower total iron-binding capacity. CLINICAL SIGNIFICANCE: Inflammation contributes to the iron status alterations found in canine leishmaniasis but other mechanisms are likely involved. Low total iron-binding capacity and increased C-reactive protein are risk factors for outcome in canine leishmaniasis.
Subject(s)
C-Reactive Protein/analysis , Dog Diseases/parasitology , Iron/blood , Leishmaniasis/veterinary , Animals , Biomarkers/blood , Case-Control Studies , Dog Diseases/blood , Dog Diseases/diagnosis , Dog Diseases/mortality , Dogs , Female , Ferritins/blood , Leishmaniasis/blood , Leishmaniasis/diagnosis , Leishmaniasis/mortality , Male , PrognosisABSTRACT
By building upon a Feynman-Kac formalism, we assess the distribution of the number of collisions in a given region for a broad class of discrete-time random walks in absorbing and nonabsorbing media. We derive the evolution equation for the generating function of the number of collisions, and we complete our analysis by examining the moments of the distribution and their relation to the walker equilibrium density. Some significant applications are discussed in detail: in particular, we revisit the gambler's ruin problem and generalize to random walks with absorption the arcsine law for the number of collisions on the half-line.
Subject(s)
Colloids/chemistry , Models, Chemical , Models, Molecular , Models, Statistical , Absorption , Computer SimulationABSTRACT
Many random transport phenomena, such as radiation propagation, chemical-biological species migration, or electron motion, can be described in terms of particles performing exponential flights. For such processes, we sketch a general approach (based on the Feynman-Kac formalism) that is amenable to explicit expressions for the moments of the number of collisions and the residence time that the walker spends in a given volume as a function of the particle equilibrium distribution. We then illustrate the proposed method in the case of the so-called rod problem (a one-dimensional system), and discuss the relevance of the obtained results in the context of Monte Carlo estimators.