An instrumental variable model of multiple discrete choice

This paper studies identification of latent utility functions in multiple discrete choice models in which there may be endogenous explanatory variables, that is explanatory variables that are not restricted to be distributed independently of the unobserved determinants of latent utilities. The model does not employ large support, special regressor or control function restrictions, indeed it is silent about the process delivering values of endogenous explanatory variables and in this respect it is incomplete. Instead the model employs instrumental variable restrictions requiring the existence of instrumental variables which are excluded from latent utilities and distributed independently of the unobserved components of utilities. We show that the model delivers set identification of the latent utility functions and we characterize sharp bounds on those functions. We develop easy-to-compute outer regions which in parametric models require little more calculation than what is involved in a conventional maximum likelihood analysis. The results are illustrated using a model which is essentially the parametric conditional logit model of McFadden (1974) but with potentially endogenous explanatory variables and instrumental variable restrictions. The method employed has wide applicability and for the first time brings instrumental variable methods to bear on structural models in which there are multiple unobservables in a structural equation.

An instrumental variable model of multiple discrete choice

This paper studies identification of latent utility functions in multiple discrete choice models in which there may be endogenous explanatory variables, that is explanatory variables that are not restricted to be distributed independently of the unobserved determinants of latent utilities. The model does not employ large support, special regressor or control function restrictions, indeed it is silent about the process delivering values of endogenous explanatory variables and in this respect it is incomplete. Instead the model employs instrumental variable restrictions requiring the existence of instrumental variables which are excluded from latent utilities and distributed independently of the unobserved components of utilities. We show that the model delivers set, not point, identification of the latent utility functions and we characterize sharp bounds on those functions. We develop easy-to-compute outer regions which in parametric models require little more calculation than what is involved in a conventional maximum likelihood analysis. The results are illustrated using a model which is essentially the parametric conditional logit model of McFadden (1974) but with potentially endogenous explanatory variables and instrumental variable restrictions. The method employed has wide applicability and for the first time brings instrumental variable methods to bear on structural models in which there are multiple unobservables in a structural equation.

Cascading effects of temperature alterations on trophic ecology of European grayling (Thymallus thymallus)

The aims of this project were to study: diet composition, food selectivity and the phenology of different prey items in grayling’s (Thymallus thymallus) diet. It was hypothesized, that alterations in mayfly emergence, caused by reservoir-induced thermal changes, have consequences for trophic ecology of drift-feeding fish. Sampling of fish and macroinvertebrates were conducted in two closely located rivers, one human-modified and the other an undisturbed river. Grayling preyed mainly on aquatic insects, but only mayflies were preferred. Seasonal changes of the fish diet were observed, and air temperature is considered a predictor of prey occurrence with different time lags, depending on the biology of the organisms. Significant differences in the abundances and probability of mayfly occurrence between two studied rivers were shown. The observed phenological shift suggests that distorted environmental cues were experienced by the Ephemeroptera in the modified river. The “lost generation” of insects which failed to complete development became a new food for fish. The results presented indicate that reservoir-induced thermal alterations in the rivers, similarly to climate change, can lead to a chain of consequences in the ecosystems. Taking into consideration the projected climate scenarios, further monitoring and forecasting of these effects are considered an important step for future mitigating actions and adaptive management of water resources.publishedVersio

Modeling of liquid chromatography separation of ziprasidone compounds using multivariate methods of principal component and hierarchical clustering analysis

Ziprasidon je novi atipični antipsihotik druge generacije, koji deluje kao antagonista na serotoninskim i dopaminskim receptorima, i inhibira preuzimanje norepinefrina. Glavni cilj hemometrijske studije je ispitivanje selektivnosti 20 reverznofaznih (RP) stacionarnih faza u odnosu na ziprazidon i šest nečistoća ((I‐V) i nepoznata). Velika strukturna sličnost ziprasidona i nečistoće II bila je ključni problem i razdvajanje kritičnog para je bilo odlučujuće za odabir RP stacionarne faze. Za analizu glavnih komponenti (PCA) korišćen je matematički program Soft Independent Modeling of Class Analogy SIMCA P+ 12.0, a za analizu hijerarhijskog grupisanja (HCA) korišćen je program MATLAB ver. 6.5. Ispitivanje selektivnosti 20 RP stacionarnih faza je vršeno pri dobijenim optimalnim eksperimentalnim uslovima (25 ºC; pH: 2,5; cTEA: 1% i cKH2PO4: 50mM) u odnosu na ispitivana jedinjenja. Eksperimentalno dobijeni hromatografski parametri (broj teoretskih platoa‐N, faktor simetrije pika ‐SF, rezolucija ‐Rs i faktor selektivnosti ‐ α između jedinjenja koja se blizu eluiraju) na 20 RP stacionarnih faza analizirani su primenom PCA i HCA analiza. Grafikoni rezultata i PCA koeficijenata variabli za PC1(osnovna komponeta 1) i PC2 (osnovna komponeta 2) pokazuju glavne razlike između svih 20 RP‐kolona i glavne sličnosti između hromatografskih parametara. Rs i α su odabrani kao najznačajniji parametri za izbor stacionarne faze. Dobijeni dendogrami pokazali su tri glavne grupe za stacionarne faze i četiri grupe za hromatografske parametre. Dendogrami RP kolona i hromatografskih parametara su prikazani i obojenom mapom što je jednostavnija metoda vizuelizacije. Određene su RP stacionarne faze posebno selektivne za efikasno razdvajanje ziprasidona i strukturno sličnih jedinjenja primenom PCA i HCA (grupa 1 PCA i grupa C AHC):Waters Spherisorb® ODS1, Waters Spherisorb® ODS2 i Nucleosil® 100‐5 C18. Dobijeni podaci su u skladu sa eksperimentalnim rezultatima. Odabrana je Waters Spherisorb® ODS 1 kolona za HPLC metodu u odnosu na najbolju SF i faktor retencije (k’).Ziprasidone is a novel „atypical” or „second generation” antipsychotic drug which acts primarily through serotonergic and dopaminergic receptor antagonism, and as an inhibitor of the norepinephrine reuptake. The main aims of the presented chemometric study was to test selectivity of the set of 20 Reversed‐phase (RP) ‐ columns towards ziprasidone and its six impurities ((I‐V) and one unknown). Separation of structurally similar pair of ziprasidone/impurity II caused analytical problems and was decisive for the selection of the suitable RP‐column. The Principal Component Analysis (PCA) for column classification was done with use of SIMCA P+ 12.0 program and Hierarchical Clustering Analysis (HCA) with use of MATLAB ver. 6.5. with additional algorithms. The obtained optimal chromatographic conditions (25C, pH 2,5, cTEA 1% and cKH2PO4 50 mM) were used to test a set of 20 RP‐columns. Plate numbers (N), symmetry factors (SF), resolution (Rs) and selectivity (α) of investigated compounds were subjected to PCA and HCA analysis. Score plot and loading plots PC1 (principal component 1) vs PC2 (principal component 2) visualize the main differences between all 20 RP‐columns and main similarities between hromatographic parameters, respectively. The Rs and α were selected as the most significant for the column selection. The obtained dendrograms reveal three distinct clusters of RP‐columns and four clusters of chromatographic parameters. The color map of data was used as a simpler presentation of the dendrograms of RP‐columns and chromatographic parameters. The RP‐columns selective for the efficient separation of ziprasidone and its structurally related compounds were defined by PCA and HCA (group 1 in PCA study and same cluster C in HCA study) : Waters Spherisorb® ODS1, Waters Spherisorb® ODS2 and Nucleosil® 100‐5 C18. The results were in accordance with experimentally obtained results. Finally, the column Waters Spherisorb® ODS 1 was selected for the HPLC method due to best SF and retention factor (k’).VII Kongres farmaceuta Srbije sa međunarodnim učešćem, Beograd, Zajedno stvaramo budućnost farmacije, 10-14. oktobar 2018

Partial Least Square and Hierarchical Clustering in ADMET Modeling: Prediction of Blood - Brain Barrier Permeation of alpha-Adrenergic and Imidazoline Receptor Ligands

PURPOSE. Rate of brain penetration (logPS), brain/plasma equilibration rate (logPS-brain), and extent of blood-brain barrier permeation (logBB) of 29 alpha-adrenergic and imidazoline-receptors ligands were examined in Quantitative-Structure-Property Relationship (QSPR) study. METHODS. Experimentally determined chromatographic retention data (logKw at pH 4.4, slope (S) at pH 4.4, logKw at pH 7.4, slope (S) at pH 7.4, logKw at pH 9.1, and slope (S) at pH 9.1) and capillary electrophoresis migration parameters (mu(eff) at pH 4.4, mu(eff) at pH 7.4, and mu(eff) at pH 9.1), together with calculated molecular descriptors, were used as independent variables in the QSPR study by use of partial least square (PLS) methodology. RESULTS. Predictive potential of the formed QSPR models, QSPR(logPS), QSPR(logPS-brain), QSPR(logBB), was confirmed by cross- and external validation. Hydrophilicity (Hy) and H-indices (H7m) were selected as significant parameters negatively correlated with both logPS and logPS-brain, while topological polar surface area (TPSA(NO)) was chosen as molecular descriptor negatively correlated with both logPS and logBB. The principal component analysis (PCA) and hierarchical clustering analysis (HCA) were applied to cluster examined drugs based on their chromatographic, electrophoretic and molecular properties. Significant positive correlations were obtained between the slope (S) at pH 7.4 and logBB in A/B cluster and between the logKw at pH 9.1 and logPS in C/D cluster. CONCLUSIONS. Results of the QSPR, clustering and correlation studies could be used as novel tool for evaluation of blood-brain barrier permeation of related alpha-adrenergic/imidazoline receptor ligands

Mine Field Preparation and Coal Mining in Western Donbas: Energy Security of Ukraine—A Case Study

Recent world trends have shown that a country’s political security depends on its fuel and energy supply. In Ukraine, these issues are managed by the United Energy System of Ukraine (USE). The USE consists of a set of power plants as well as electric and thermal networks operating in the general mode of production, transmission and distribution of electric and thermal energy. Nuclear power plants (NPPs), thermal power plants (TPPs), hydroelectric power plants (HPPs), thermal power plants (CHPs), as well as power plants run on alternative (renewable) sources of electricity (solar, wind, bio- and others). They are operating in one system. All of them are connected by the main electric networks. Thermal power plants (TPPs) produce nearly 27% of all electrical energy in Ukraine [1]. Recently, the amount of commercial coal required by Ukraine’s energy sector has increased from 19 to 21 million tons. In 2021, coal production had decreased by approximately 7.7% compared to 2020. Accordingly, this requires the import of coal [1]. Therefore, increasing the efficiency of coal mining is an urgent scientific and practical task.Ukrainian electricity production sector is in a critical situation. It is necessary to increase the coal production to ensure the continuity of electricity production. In this paper, an analysis of coal mining in western Donbas, Ukraine, was presented. The crucial thing is to increase coal production in this region. The new calculation schemes were proposed to increase coal extraction in Donbas mines. The coal pillar parameters, which are necessary for the effective control of the rock pressure caused by the stooping, were substantiated. The obtained parameters for the coal pillars will allow extracting more coal, safely and quickly dismantling the mechanized complex and effectively protecting the ongoing mine work. The case study helps determine the coal losses because of pillar leaving and to improve the stability of the main haulage roads located in the zone of the stooping effect as well as to achieve additional coal production in the mine. Such a technological solution allows to extract the coal more fully at the final parts of the extractive columns and to obtain an additional economic effect. The increase in coal production in coal mines of western Donbas will increase the energy security of all Ukraine

Towards Arginase Inhibition: Hybrid SAR Protocol for Property Mapping of Chlorinated N-arylcinnamamides

peer reviewedA series of seventeen 4-chlorocinnamanilides and seventeen 3,4-dichlorocinnamanilides were characterized for their antiplasmodial activity. In vitro screening on a chloroquine-sensitive strain of Plasmodium falciparum 3D7/MRA-102 highlighted that 23 compounds possessed IC50 < 30 µM. Typically, 3,4-dichlorocinnamanilides showed a broader range of activity compared to 4-chlorocinnamanilides. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-en-amide with IC50 = 1.6 µM was the most effective agent, while the other eight most active derivatives showed IC50 in the range from 1.8 to 4.6 µM. A good correlation between the experimental logk and the estimated clogP was recorded for the whole ensemble of the lipophilicity generators. Moreover, the SAR-mediated similarity assessment of the novel (di)chlorinated N-arylcinnamamides was conducted using the collaborative (hybrid) ligand-based and structure-related protocols. In consequence, an ‘averaged’ selection-driven interaction pattern was produced based in namely ‘pseudo–consensus’ 3D pharmacophore mapping. The molecular docking approach was engaged for the most potent antiplasmodial agents in order to gain an insight into the arginase-inhibitor binding mode. The docking study revealed that (di)chlorinated aromatic (C-phenyl) rings are oriented towards the binuclear manganese cluster in the energetically favorable poses of the chloroquine and the most potent arginase inhibitors. Additionally, the water-mediated hydrogen bonds were formed via carbonyl function present in the new N-arylcinnamamides and the fluorine substituent (alone or in trifluoromethyl group) of N-phenyl ring seems to play a key role in forming the halogen bonds

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version