bluuebunny/crossref_metadata_2025 huggingface dataset:
Reaction of 1,4-dibromohexafluoro-2-butene with O- and N-nucleophiles
Authors: Hemer Ivan , Moravcová Věra , Dědek Václav
Published: June 2010

Reaction of 1,4-dibromohexafluoro-2-butene (I) with sodium methoxide, ethoxide or isopropoxide in the corresponding alcohols proceeds with allylic rearrangement under formation of 3-alkoxy-4-bromohexafluoro-1-butenes II-IV. A kinetic study has proven the SN2’ mechanism for reaction of I with potassium phenoxide leading to 4-bromo-3-phenoxyhexafluoro-1-butene (V). Also the reaction of I with ammonia, affording 3-amino-4-bromo-2,4,4-trifluoro-2-butenenitrile (IX), is compatible with the allylic rearrangement by SN2’ mechanism. On the contrary, reaction of I with diethylamine gave no rearrangement product and, after hydrolysis, afforded N,N-diethyl-4-bromo-2,3,3,4,4-pentafluorobutanamide (XVI) and N,N-diethyl-4-bromo-2,3,4,4-tetrafluoro-2-butenamide (XVII) in the ratio 85:15.
Preparation of 1’- and 2-substituted ferrocenylalanine derivatives
Authors: Kaluz Štefan , Toma Štefan
Published: June 2010

Synthesis of N-formyl derivatives of racemic 1,1’-ferrocenedialanine, 1,2-ferrocenedialanine, and 1’-carboxyferrocenylalanine is described. The synthesis started from 1,1’-, 1,2-bis(hydroxymethyl)ferrocene, and methyl 1’-(hydroxymethyl)ferrocenecarboxylate, respectively.
Synthesis of 6-aryl-6H-naphtho[2’,1’:5,6]pyrano[4,3-b]-[1,8]naphthyridines
Authors: Reddy Kamreddy Rajendar , Mogilaiah Kaleru , Sreenivasulu Bathula
Published: June 2010

A series of new 6-aryl-6H-naphtho[2’,1’:5,6]pyrano[4,3-b][1,8]naphthyridines III have been synthesized by condensing 2-aminonicotinaldehyde (I) with a number of 1-hydroxy-2-naphthyl styryl ketones II in the presence of glacial acetic acid containing a catalytic amount of conc. sulphuric acid. The products have been characterized on the basis of elemental analyses and spectral data. Antibacterial activity of these compounds is negligible.
Hydraulic model of a water cooling system in a chemical plant
Authors: Hošťálek Miloslav , Výborný Jiří , Madron František
Published: June 2010

Steady state hydraulic calculation has been described of an extensive pipeline network based on a new graph algorithm for setting up and decomposition of balance equations of the model. The parameters of the model are characteristics of individual sections of the network (pumps, pipes, and heat exchangers with armatures). In case of sections with controlled flow rate (variable characteristic), or sections with measured flow rate, the flow rates are direct inputs. The interactions of the network with the surroundings are accounted for by appropriate sources and sinks of individual nodes. The result of the calculation is the knowledge of all flow rates and pressure losses in the network. Automatic generation of the model equations utilizes an efficient (vector) fixing of the network topology and predominantly logical, not numerical operations based on the graph theory. The calculation proper utilizes a modification of the model by the method of linearization of characteristics, while the properties of the modified set of equations permit further decrease of the requirements on the computer. The described approach is suitable for the solution of practical problems even on lower category personal computers. The calculations are illustrated on an example of a simple network with uncontrolled and controlled flow rates of cooling water while one of the sections of the network is also a gravitational return flow of the cooling water.
A study of nucleophilicity in selected systems
Authors: Zima Vítězslav , Pytela Oldřich , Večeřa Miroslav
Published: June 2010

Kinetic studies have been carried out of the reactions of 15 nucleophiles with 2,4-dinitrophenyl acetate and 14 nucleophiles with 2,4-dinitrofluorobenzene in 52% (w/w) methanol at 25 °C. The rate constant values obtained and literature data have been treated by the factor analysis. It has been found that the description of nucleophilicity at least needs two factors. The nucleophiles studied are divided into two groups (ionic and nitrogen-containing ones). In each group, the nucleophilic properties are affected by linear combination of both factors.
The process of coalescence of dense liquid dispersions
Authors: Míšek Tomáš , Rod Vladimír
Published: June 2010

Physical and mathematical models have been derived and experimentally confirmed for the formation of the hold-up profile in a dense liquid-liquid dispersion and for the rate of coalescence at the interface. Both processes may be characterized by three parameters which can be verified or determined experimentally and further used for design of an industrial unit.
The comparison of two preparations of a Ni-Co-Mo/Al2O3-SiO2 hydrotreating catalysts
Authors: Grzechowiak Jolanta , Sedláček Jiří , Zdražil Miroslav
Published: June 2010

Two preparations of Ni-Co-Mo/Al2O3-SiO2 hydrorefining catalysts differing in the method of SiO2 addition were investigated by the combination of several chemical and physical methods. As the result of the modification in preparation procedure, the following changes occurred simultaneously: the increase of relative surface concentrations of active metals detected by XPS, the increase of surface acidity measured by ammonia thermodesorption, the increase in porosity, the formation of larger pores, enlargement of the particles forming the texture of surface shown by SEM and the increase of the rate of hydrodesulphurization of tetrahydrothiophene. The response of other characteristics was small: surface polarity measured by reversible adsorption of benzene and heptane, the rate of hydrodesulphurization of thiophene and the rate of decomposition of tetrahydrothiophene in nitrogen. The difference in the performance of both catalysts is explained by the combination of several factors. The necessity of combination of several characterization techniques in the study of the relation between preparation procedure and performance of the catalyst is stressed.
Radiation polymerization of 2-hydroxyethyl methacrylate-vinyl pyrrolidone-water system
Authors: Kumakura Minoru , Kaetsu Isao
Published: June 2010

Radiation polymerization of 2-hydroxyethyl methacrylate-vinyl pyrrolidone-water system at low temperature was studied. The polymerization rate-irradiation temperature curve had a maximum peak at near glass transition temperaure, and it was shifted to the site of high temperature with increasing monomer concentration. The polymerization rate in vinyl pyrrolidone at low temperatures was accelerated by the addition of water. The polymers obtained by radiation polymerization of 2-hydroxyethyl methacrylate-vinyl pyrrolidone-water system at low temperatures were a high hydrophilicity and had porous structure.
Polarography of the oxytocin and vasopressin synthetic analogs
Authors: Mader Pavel , Veselá Věra , Heyrovský Michael , Lebl Michal , Braunsteinová Milena
Published: June 2010

Small changes in the molecules of the oxytocin and vasopressin synthetic analogs bring about considerable changes in their polarographic behaviour within the entire potential interval available (+0·5 to -2·0 V VS SCE). In the study of the polarographic activity of ten peptides we used classical, differential pulse and alternating current polarography and cyclic voltammetry. Liquid chromatographic separation studies of the peptides on the reverse phase complemented the electrochemical investigation. Hydrophobicity showed to be the parameter which decisively influences the polarographic behaviour of the studied peptides. Strong interaction of the SS and S-carba analogs with the electrode material (mercury) has been observed and surface activity of the SH-forms of the peptides at negative potentials has been confirmed. The importance of various functional groups in the peptide molecule for the catalytic activity in hydrogen evolution at negative potentials is discussed.
On the accuracy of conventional calculations of potential energy surfaces
Authors: Landscheid Ulf , Kutzelnigg Werner
Published: June 2010

It is demonstrated for the example of H2+ that with the conventional basis expansion method (in terms of Gaussians) with fixed non-linear parameters the error of a computed potential curve varies strongly with the geometry. If the non-linear parameters are optimized for the equilibrium geometry, much larger errors arise for other geometries. This is very pronounced if only one polarization function of a given l is added to the basis, and qualitatively the same problem arises for any new l. The dependence of the error on the distance may also be oscillatory. For the example of Li2 in the SCF or an MC-SCF approximation essentially the same effects are observed. Here in addition substantial errors for large R may arise in the SCF curve if the basis is not able to describe the spurious ionic contributions.
Electron density analysis of substituent effects in substituted benzenes
Authors: Streitwieser Andrew , Vorpagel Erich R.
Published: June 2010

Electron projection functions and the corresponding difference functions relative to benzene are computed for π and σ electronic systems of several substituted benzenes, fluorobenzene, toluene and anilinium cation, and idealized model substituents, benzene with an external point positive charge and benzene with an external dipole. The results are plotted and integrated difference populations are compared with Mulliken populations. The later give good agreement, especially for π-systems, but obscure the underlying polarization especially evident in σ systems.
Electronegativities of diatomic molecules calculated by the Xα method with a self-consistent parameter α using the principle of electronegativity equalization
Authors: Gáspár Rezsö , Nagy Ágnes
Published: June 2010

The Xα method with a self-consistent parameter α has been used to calculate the electronegativity of several diatomic molecules. The electronegativities have been determined on the principle of electronegativity equalization using the results of atomic calculations.
Vibrational properties of surface hydroxyls: Nonempirical model calculations including anharmonicities
Authors: Mix Hartmut , Sauer Joachim , Schröder Klaus-Peter , Merkel Angela
Published: June 2010

Complete sets of harmonic, semidiagonal cubic as well as diagonal cubic and quartic force constants are reported for the internal coordinates of terminal, ≣SiOH, and bridging, ≣SiOH·Al≣, surface hydroxyls on silica and zeolites. They are obtained by numerical differentiation of analytically calculated gradients of the energy (SCF approximation, 6-31 G* basis set). A GF vibrational analysis is performed and after making a nonlinear transformation of the force constants into normal coordinates the anharmonicity constants are evaluated by perturbation theory. Comparison is made with the D2OH+ ion and the DOH molecule. The calculated anharmonicities of the OH bonds in the systems studied are remarkably constant and vary between -76 and -84 cm-1, only in agreement with the values observed for DOH (-83 cm-1) and surface silanols, ≣SiOH (-90 ± 15 cm-1).
On the nature of the bonding in X-Be-O molecules (X = He, Ne, Ar)
Authors: Hobza Pavel , Schleyer Paul von Ragué
Published: June 2010

The noble gas complexes, HeBeO, NeBeO, and ArBeO, discovered calculationally by Koch and Frenking, were reexamined at various theoretical levels. The results depended strongly on the size of the basis set but were insensitive to electron correlation corrections. The MP2 association energies of BeO with the noble gases, obtained with extended basis sets, were 4·80, 4·76, and 10·12 kcal/mol, respectively. The surprising stability of HeBeO (compared to NeBeO) is due to greater charge-transfer from He to BeO (donation) as well as to charge-transfer in the reverse direction (back donation). This compensates for the larger induction energy due to the greater polarizability of neon. The basis set superposition error is very large with split-valence basis sets; improvement of s and p function descriptions strongly reduces but does not completely eliminate this error.
Heat of interaction of oxygen with dysprosium and yttrium
Authors: Černý Slavoj , Kovář Milan
Published: June 2010

Heat of interaction of oxygen dosed to vacuum-evaporated films of dysprosium and yttrium were measured in a calorimeter at room temperature. The high and rapidly produced heat, and the attained oxygen-to-metal ratio indicate high reactivity of these rare earth metals towards oxygen molecules which obviously undergo dissociative sorption. The energy of bonding of the formed oxygen species to the metal was estimated to 723 kJ/mol (173 kcal/mol) and 780 kJ/mol (186 kcal/mol) for Dy and Y, respectively. A markedly higher sorption capacity of Y film compared to Dy film was observed. The heat produced by the first admitted doses of oxygen may suggest formation of a solid solution of oxygen species in Dy and Y at very low oxygen-to-metal ratios.
Information content of the determinations of the amount of an analyte
Authors: Eckschlager Karel , Fusek Jiří
Published: June 2010

It is shown how the information content expressed in terms of the extended divergence measure I(r; p, p0) depends on the amount of the component to be determined when homoscedastic and heteroscedastic dependences of the analytical signal on the amount of the analyte are distinguished. The importance of the accuracy is pointed out, with which the amount of the analyte is known in a reference material employed for testing a particular analytical method. Rules are set, the maintaining of which is aimed at avoiding the origin of null information content of analytical results.
Determination of 134Cs and 137Cs in milk by sorption on freshly prepared precipitate of Cu(II) hexacyanoferrate in combination with gamma spectrometry
Authors: Hölgye Zoltán , Drábová Dana
Published: June 2010

A simple and rapid method for the determination of 134Cs and 137Cs in cow's milk has been worked out. The method is based on the separation of radiocaesium from milk by sorption on a freshly prepared precipitate of Cu(II) hexacyanoferrate, on the separation of the precipitate by centrifugation, and on the gamma-spectrometric measurement of the precipitate activity.
Determination of the structure of p-methylbenzamidinium formate monohydrate
Authors: Kratochvíl Bohumil , Ondráček Jan , Hašek Jindřich , Csordás László
Published: June 2010

The molecular and crystal structure of p-methylbenzamidinium formate monohydrate, C9H14N2O3, was solved by direct methods. The positions of all the atoms were localized and the structure was refined anisotropically. The final value of the R factor equalled 0·043 for 1 150 observed reflections (I > 1·96σ(I)). The substance crystallizes in the P21/c monoclinic space group with lattice parameters a = 1 038·9(4), b = 1 146·1(5), c = 912·4(3) pm, β = 94·77(3)0, Z = 4. The molecule contains an amidinium-carboxylate bond, formed by two intramolecular hydrogen bridges of the N-H···O type. Intermolecular hydrogen bonds are formed by the side hydrogen atoms of the amidine and the hydrogen atoms of the water molecule and are of the N-H···O and O-H···O types; they form a three-dimensional network in the crystal structure. In this, the structure of p-methylbenzamidinium formate monohydrate differs from the related structures of benzamidinium pyruvate and benzamidinium bromoacetate, characterized by infinite intermolecular chains formed through hydrogen bonding.
The use of a potassium ion selective electrode for measuring kinetic parameters of enzymatic hydrolysis of butyrylcholine
Authors: Kellner Josef
Published: June 2010

The suitability of a Crytur 19-15 potassium ion selective electrode for indication of the course of enzymatic hydrolysis of butyrylcholine is demonstrated. The electrode can be also used at high initial concentrations of substrate. Procedures for experimental data handling are suggested.
Malnutrition and nutrition support in patients with liver disease
Authors: Saunders John , Brian Anna , Wright Mark , Stroud Mike
Published: June 2010

Liver disease, especially alcohol related, is increasingly common and is often accompanied by malnutrition as a result of reduced intake, absorption, processing and storage of nutrients. An increase or alteration in metabolic demands also occurs and some patients have high nutrient losses. Malnutrition in all forms of liver disease is associated with higher rates of mortality and morbidity but it is often under recognised and under treated despite the fact that appropriate treatment can improve outcomes. In this review, the causes, consequences and assessment of nutritional status in patients with liver disease are examined, and an approach to best treatment is proposed.
Thrills, spills and pills: Bond, Benzedrine and the pharmacology of peace
Authors: Goodman Sam
Published: June 2010

This paper examines the conjunction of pharmacological science and espionage fiction of the post-war era. This paper argues that, during the 1950s, the relatively new science of pharmacology propounded the possibility that illness and human deficiency could be treated in a way that better reflected the post-war zeitgeist. The use of pharmacological medicine, perceived as cleaner and quicker than more ‘bodily’ forms of treatment, represented progress in contemporary medical science. It is argued that this philosophy extended to more overt means of pharmacological application, directly related to the geopolitical concerns of the ‘Cold War’. A growing form of popular literature in this period was the espionage novel. This paper argues that the benefits proffered by pharmacology were incorporated into the fabric of espionage fiction, specifically the James Bond novels of Ian Fleming. Here, it is demonstrated how Fleming used pharmacological knowledge of Benzedrine throughout his novels. His works illustrate a belief that the augmentation of the spy's natural ability with pharmacological science would award decisive advantage in the Cold War conflict played out in spy fiction. However, the relationship between public use of Benzedrine and awareness of its side effects changed during the period of Fleming's publications, moving from a position of casual availability to one of controlled prescription. It is argued that the recognition of the dangers associated with the drug were over-ruled in favour of the benefits its use presented to the state. The continued use of the drug by Bond illustrates how the concerns of the nation are given priority over the health, and life, of the individual.
後金融海嘯失業問題研究 — 從外國經驗給予香港建立失業保障制度的啟示
Authors: 歐陽 達初 , 黃 碩紅 , 陳 嘉祺
Published: June 2010

未提供摘要。
A Linguistically Inspired Statistical Model for Chinese Punctuation Generation
Authors: Guo Yuqing , Wang Haifeng , van Genabith Josef
Published: June 2010

This article investigates a relatively underdeveloped subject in natural language processing---the generation of punctuation marks. From a theoretical perspective, we study 16 Chinese punctuation marks as defined in the Chinese national standard of punctuation usage, and categorize these punctuation marks into three different types according to their syntactic properties. We implement a three-tier maximum entropy model incorporating linguistically-motivated features for generating the commonly used Chinese punctuation marks in unpunctuated sentences output by a surface realizer. Furthermore, we present a method to automatically extract cue words indicating sentence-final punctuation marks as a specialized feature to construct a more precise model. Evaluating on the Penn Chinese Treebank data, the MaxEnt model achieves an
f
-score of 79.83% for punctuation insertion and 74.61% for punctuation restoration using gold data input, 79.50% for insertion and 73.32% for restoration using parser-based imperfect input. The experiments show that the MaxEnt model significantly outperforms a baseline 5-gram language model that scores 54.99% for punctuation insertion and 52.01% for restoration. We show that our results are not far from human performance on the same task with human insertion
f
-scores in the range of 81-87% and human restoration in the range of 71-82%. Finally, a manual error analysis of the generation output shows that close to 40% of the mismatched punctuation marks do in fact result in acceptable choices, a fact obscured in the automatic string-matching based evaluation scores.
The spoken web
Authors: Agarwal Sheetal K. , Jain Anupam , Kumar Arun , Nanavati Amit A. , Rajput Nitendra
Published: June 2010

Spoken Web proposes to build an alternate web for the underprivileged population that is yet untouched by the enormous benefits of Internet and World Wide Web. Just over 22% of World's population today has access to Internet [Stats 2008]. The remaining 78% either cannot afford computers or high end mobiles, or are textually illiterate or simply reside in areas where basic infrastructure (such as electricity) is not available.
"Tools, Metrics, Context-Awareness and Applications for Web Accessibility Assessment" by Markel Vigo with Jessica Rubart as Coordinator
Authors: Vigo Markel
Published: June 2010

The PhD thesis entitled "Automatic Assessment of Contextual Web Accessibility from an Evaluation, Measurement and Adaptation Perspective" was completed while at the University of the Basque Country (Spain) in November 2009 under the supervision of Professor Julio Abascal.
Estimation-based metaheuristics for stochastic combinatorial optimization
Authors: Balaprakash Prasanna
Published: June 2010

In stochastic combinatorial optimization, problem parameters are affected by uncertainty; however, probability distributions describing the uncertainty are known or can be estimated. Stochastic routing problems, a prominent class of stochastic combinatorial optimization problems, involve finding an efficient way to distribute or collect goods across a logistic network. In order to tackle these problems, I considered a typical setting in which the cost of each solution is a random variable, and the goal is to find the solution with the minimum expected cost. It has been shown that, for some problems and for known probability distributions, the expectation can be computed analytically. Unfortunately, this typically involves complex analytical developments and computationally expensive procedures. Moreover, computing the expectation through the analytical computation approach is a highly problem-specific issue and it requires a deep understanding of the underlying probabilistic model. An alternative approach is empirical estimation, which estimates the expectation through Monte Carlo simulation. The main advantage of the empirical estimation approach over the analytical computation one is generality: a sample estimate of the expected cost of a given solution can be obtained by simply averaging sample cost estimates over a number of realizations of the random variable.
Structural Complexities in the Active Layers of Organic Electronics
Authors: Lee Stephanie S. , Loo Yueh-Lin
Published: June 2010

The field of organic electronics has progressed rapidly in recent years. However, understanding the direct structure-function relationships between the morphology in electrically active layers and the performance of devices composed of these materials has proven difficult. The morphology of active layers in organic electronics is inherently complex, with heterogeneities existing across multiple length scales, from subnanometer to micron and millimeter range. A major challenge still facing the organic electronics community is understanding how the morphology across all of the length scales in active layers collectively determines the device performance of organic electronics. In this review we highlight experiments that have contributed to the elucidation of structure-function relationships in organic electronics and also point to areas in which knowledge of such relationships is still lacking. Such knowledge will lead to the ability to select active materials on the basis of their inherent properties for the fabrication of devices with prespecified characteristics.
Nanocomposites: Structure, Phase Behavior, and Properties
Authors: Kumar Sanat K. , Krishnamoorti Ramanan
Published: June 2010

It is well recognized that nanocomposites formed by adding nanoparticles to polymers can have significantly enhanced properties relative to the native polymer. This review focuses on three aspects that are central to the outstanding problem of realizing these promised property improvements. First, we ask if there exist general strategies to control nanoparticle spatial distribution. This is an important question because it is commonly accepted that the nanoparticle dispersion state crucially affects property improvements. Because ideas on macroscale composites suggest that optimizing different properties requires different dispersion states, we next ask if we can predict a priori the particle dispersion and organization state that can optimize one (or more) properties of the resulting nanocomposite. Finally, we examine the role that particle shape plays in affecting dispersion and hence property control. This review focuses on recent advances concerning these underpinning points and how they affect measurable properties relevant to engineering applications.
Design Rules for Biomolecular Adhesion: Lessons from Force Measurements
Authors: Leckband Deborah
Published: June 2010

Cell adhesion to matrix, other cells, or pathogens plays a pivotal role in many processes in biomolecular engineering. Early macroscopic methods of quantifying adhesion led to the development of quantitative models of cell adhesion and migration. The more recent use of sensitive probes to quantify the forces that alter or manipulate adhesion proteins has revealed much greater functional diversity than was apparent from population average measurements of cell adhesion. This review highlights theoretical and experimental methods that identified force-dependent molecular properties that are central to the biological activity of adhesion proteins. Experimental and theoretical methods emphasized in this review include the surface force apparatus, atomic force microscopy, and vesicle-based probes. Specific examples given illustrate how these tools have revealed unique properties of adhesion proteins and their structural origins.
Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice
Authors: Ceppa Eugene , Cattaruzza Fiore , Lyo Victoria , Amadesi Silvia , Pelayo Juan-Carlos , Poole Daniel P. , Vaksman Natalya , Liedtke Wolfgang , Cohen David M. , Grady Eileen F. , Bunnett Nigel W. , Kirkwood Kimberly S.
Published: June 2010

The mechanisms of pancreatic pain, a cardinal symptom of pancreatitis, are unknown. Proinflammatory agents that activate transient receptor potential (TRP) channels in nociceptive neurons can cause neurogenic inflammation and pain. We report a major role for TRPV4, which detects osmotic pressure and arachidonic acid metabolites, and TRPA1, which responds to 4-hydroxynonenal and cyclopentenone prostaglandins, in pancreatic inflammation and pain in mice. Immunoreactive TRPV4 and TRPA1 were detected in pancreatic nerve fibers and in dorsal root ganglia neurons innervating the pancreas, which were identified by retrograde tracing. Agonists of TRPV4 and TRPA1 increased intracellular Ca2+ concentration ([Ca2+]i) in these neurons in culture, and neurons also responded to the TRPV1 agonist capsaicin and are thus nociceptors. Intraductal injection of TRPV4 and TRPA1 agonists increased c-Fos expression in spinal neurons, indicative of nociceptor activation, and intraductal TRPA1 agonists also caused pancreatic inflammation. The effects of TRPV4 and TRPA1 agonists on [Ca2+]i, pain and inflammation were markedly diminished or abolished in trpv4 and trpa1 knockout mice. The secretagogue cerulein induced pancreatitis, c-Fos expression in spinal neurons, and pain behavior in wild-type mice. Deletion of trpv4 or trpa1 suppressed c-Fos expression and pain behavior, and deletion of trpa1 attenuated pancreatitis. Thus TRPV4 and TRPA1 contribute to pancreatic pain, and TRPA1 also mediates pancreatic inflammation. Our results provide new information about the contributions of TRPV4 and TRPA1 to inflammatory pain and suggest that channel antagonists are an effective therapy for pancreatitis, when multiple proinflammatory agents are generated that can activate and sensitize these channels.
The importance of endothelin axis in initiation, progression, and therapy of ovarian cancer
Authors: Rosanò Laura , Spinella Francesca , Bagnato Anna
Published: June 2010

The endothelin-1 (ET-1)/ET A receptor (ETAR) axis is involved in the pathobiology of different tumors, including ovarian carcinoma. Acting selectively on ETAR, ET-1 regulates, through multiple signaling pathways, mitogenesis, cell survival, angiogenesis, lymphangiogenesis, invasion, and metastatic dissemination. Moreover, ET-1/ETAR axis appears to be critical in epithelial-to-mesenchymal transition (EMT), providing a mechanism of escape to a new, less adverse niche, in which resistance to apoptosis ensures cell survival in conditions of stress in the primary tumor, and acquisition of “stemness” ensures generation of the critical mass required for tumor progression. Emerging experimental and preclinical data demonstrate that interfering with ETAR pathways provides an opportunity for the development of new mechanism-based antitumor strategies by using ETAR antagonists alone and in combination with cytotoxic drugs or molecular inhibitors. A specific ETAR antagonist in combination with standard chemotherapy is currently evaluated in clinical and translational studies to provide us with new options to treat ovarian cancer and to predict response to therapy. Deeper understanding of molecular mechanism activated by ETAR in ovarian cancer will be of paramount importance in the study of ETAR-targeted therapy that, regulating EMT and other tumor-associated processes, represents an attractive but challenging approach to improve clinical management of ovarian cancer.
Calculating alveolar capillary conductance and pulmonary capillary blood volume: comparing the multiple- and single-inspired oxygen tension methods
Authors: Ceridon Maile L. , Beck Kenneth C. , Olson Thomas P. , Bilezikian Jordan A. , Johnson Bruce D.
Published: June 2010

Key elements for determining alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) from the lung diffusing capacity (Dl) for carbon monoxide (DlCO) or for nitric oxide (DlNO) are the reaction rate of carbon monoxide with hemoglobin (θCO) and the DmCO/DlNOrelationship (α-ratio). Although a range of values have been reported, currently there is no consensus regarding these parameters. The study purpose was to define optimal parameters (θCO, α-ratio) that would experimentally substantiate calculations of Dm and Vc from the single-inspired O2tension [inspired fraction of O2(FiO2)] method relative to the multiple-FiO2method. Eight healthy men were studied at rest and during moderate exercise (80-W cycle). Dm and Vc were determined by the multiple-FiO2and single-FiO2methods (rebreathe technique) and were tabulated by applying previously reported θCOequations (both methods) and by varying the α-ratio (single-FiO2method) from 1.90 to 2.50. Values were then compared between methods throughout the examined α-ratios. Dm and Vc were critically dependent on the applied θCOequation. For the multiple-FiO2method, Dm was highly variable between θCOequations (rest and exercise); the range of Vc was less widespread. For the single-FiO2method, the θCOequation by Reeves and Park (1992) combined with an α-ratio between 2.08 and 2.26 gave values for Dm and Vc that most closely matched those from the multiple-FiO2method and were also physiologically plausible compared with predicted values. We conclude that the parameters used to calculate Dm and Vc values from the single-FiO2method (using DlCOand DlNO) can significantly influence results and should be evaluated within individual laboratories to obtain optimal values.
Predicting Any Arm Movement Feedback to Induce Three-Dimensional Illusory Movements in Humans
Authors: Thyrion Chloé , Roll Jean-Pierre
Published: June 2010

Our sense of body posture and movement is mainly mediated by densely packed populations of tiny mechanoreceptors present in the muscles. Signals triggered in muscle spindles by our own actions contribute crucially to our consciousness of positions and movements by continuously feeding and updating dynamic sensorimotor maps. Deciphering the coding rules whereby the nervous system integrates this proprioceptive information perceptually could help to elucidate the mechanisms underlying kinesthesia. The aim of the present study was to test the validity of a “propriomimetic method” of predicting the proprioceptive streams emitted by each of the muscles involved in two- (2D) and three-dimensional (3D) arm movements. This method was based on the functional properties of muscle spindle populations previously recorded microneurographically in behaving humans. Ia afferent patterns mimicking those evoked when the “arm–forearm” ensemble is drawing straight lines, graphic symbols, and complex 3D figures were calculated. These simulated patterns were then delivered to the main elbow and shoulder muscle tendons of motionless volunteers via a set of vibrators. Results show that the simulated proprioceptive patterns applied induced, in passive subjects, illusory 2D and 3D arm movements, the trajectories of which were very similar to the expected ones. These simulated patterns can therefore be said to be a substitute for the Ia proprioceptive feedback evoked by any human arm movement and this method can certainly be extended to other musculoskeletal ensembles. The illusory movements induced when these proprioceptive patterns are applied to muscle groups via sets of vibrators may provide useful tools for sensorimotor rehabilitation purposes.
Delayed Visual Feedback Affects Both Manual Tracking and Grip Force Control When Transporting a Handheld Object
Authors: Sarlegna Fabrice R. , Baud-Bovy Gabriel , Danion Frédéric
Published: June 2010

When we manipulate an object, grip force is adjusted in anticipation of the mechanical consequences of hand motion (i.e., load force) to prevent the object from slipping. This predictive behavior is assumed to rely on an internal representation of the object dynamic properties, which would be elaborated via visual information before the object is grasped and via somatosensory feedback once the object is grasped. Here we examined this view by investigating the effect of delayed visual feedback during dextrous object manipulation. Adult participants manually tracked a sinusoidal target by oscillating a handheld object whose current position was displayed as a cursor on a screen along with the visual target. A delay was introduced between actual object displacement and cursor motion. This delay was linearly increased (from 0 to 300 ms) and decreased within 2-min trials. As previously reported, delayed visual feedback altered performance in manual tracking. Importantly, although the physical properties of the object remained unchanged, delayed visual feedback altered the timing of grip force relative to load force by about 50 ms. Additional experiments showed that this effect was not due to task complexity nor to manual tracking. A model inspired by the behavior of mass-spring systems suggests that delayed visual feedback may have biased the representation of object dynamics. Overall, our findings support the idea that visual feedback of object motion can influence the predictive control of grip force even when the object is grasped.
In Vivo Dynamic Clamp Study of Ih in the Mouse Inferior Colliculus
Authors: Nagtegaal A. P. , Borst J.G.G.
Published: June 2010

Approximately half of the cells in the mouse inferior colliculus have the hyperpolarization-activated mixed cation current Ih, yet little is known about its functional relevance in vivo. We therefore studied its contribution to the processing of sound information in single cells by making in vivo whole cell recordings from the inferior colliculus (IC) of young-adult anesthetized C57Bl/6 mice. Following pharmacological block of the endogenous channels, a dynamic clamp approach allowed us to study the responses to current injections or auditory stimuli in the presence and absence of Ih within the same neuron, thus avoiding network or developmental effects. The presence of Ih changed basic cellular properties, including depolarizing the resting membrane potential and decreasing resting membrane resistance. Sound-evoked excitatory postsynaptic potentials were smaller but at the same time reached a more positive membrane potential when Ih was present. With Ih, a subset of cells showed rebound spiking following hyperpolarizing current injection. Its presence also changed more complex cellular properties. It decreased temporal summation in response to both hyperpolarizing and depolarizing repetitive current stimuli, and resulted in small changes in the cycle-averaged membrane potential during sinusoidal amplitude modulated (SAM) tones. Furthermore, Ih minimally decreased the response to a tone following a depolarization, an effect that may make a small contribution to forward masking. Our results thus suggest that previously observed differences in IC cells are a mixture of direct effects of Ih and indirect effects due to the change in membrane potential or effects due to the co-expression with other channels.
Adrenergic Receptor-Mediated Disinhibition of Mitral Cells Triggers Long-Term Enhancement of Synchronized Oscillations in the Olfactory Bulb
Authors: Pandipati Sruthi , Gire David H. , Schoppa Nathan E.
Published: June 2010

Norepinephrine (NE) is widely implicated in various forms of associative olfactory learning in rodents, including early learning preference in neonates. Here we used patch-clamp recordings in rat olfactory bulb slices to assess cellular actions of NE, examining both acute, short-term effects of NE as well as the relationship between these acute effects and long-term cellular changes that could underlie learning. Our focus for long-term effects was on synchronized gamma frequency (30–70 Hz) oscillations, shown in prior studies to be enhanced for up to an hour after brief exposure of a bulb slice to NE and neuronal stimulation. In terms of acute effects, we found that a dominant action of NE was to reduce inhibitory GABAergic transmission from granule cells (GCs) to output mitral cells (MCs). This disinhibition was also induced by clonidine, an agonist specific for α2adrenergic receptors (ARs). Acute NE-induced disinhibition of MCs appeared to be linked to long-term enhancement of gamma oscillations, based, first, on the fact that clonidine, but not agonists specific for other AR subtypes, mimicked NE's long-term actions. In addition, the α2AR-specific antagonist yohimbine blocked the long-term enhancement of the oscillations due to NE. Last, brief exposure of the slice to the GABAAreceptor antagonist gabazine, to block inhibitory synapses directly, also induced the long-term changes. Acute disinhibition is a plausible permissive effect of NE leading to olfactory learning, because, when combined with exposure to a specific odor, it should lead to neuron-specific increases in intracellular calcium of the type generally associated with long-term synaptic modifications.
The Effect of Attention on Neuronal Responses to High and Low Contrast Stimuli
Authors: Lee Joonyeol , Maunsell John H. R.
Published: June 2010

It remains unclear how attention affects the tuning of individual neurons in visual cerebral cortex. Some observations suggest that attention preferentially enhances responses to low contrast stimuli, whereas others suggest that attention proportionally affects responses to all stimuli. Resolving how attention affects responses to different stimuli is essential for understanding the mechanism by which it acts. To explore the effects of attention on stimuli of different contrasts, we recorded from individual neurons in the middle temporal visual area (MT) of rhesus monkeys while shifting their attention between preferred and nonpreferred stimuli within their receptive fields. This configuration results in robust attentional modulation that makes it possible to readily distinguish whether attention acts preferentially on low contrast stimuli. We found no evidence for greater enhancement of low contrast stimuli. Instead, the strong attentional modulations were well explained by a model in which attention proportionally enhances responses to stimuli of all contrasts. These data, together with observations on the effects of attention on responses to other stimulus dimensions, suggest that the primary effect of attention in visual cortex may be to simply increase the strength of responses to all stimuli by the same proportion.
Pulmonary Surfactant Pathophysiology: Current Models and Open Questions
Authors: Perez-Gil Jesús , Weaver Timothy E.
Published: June 2010

Pulmonary surfactant is an essential lipid-protein complex that stabilizes the respiratory units (alveoli) involved in gas exchange. Quantitative or qualitative derangements in surfactant are associated with severe respiratory pathologies. The integrated regulation of surfactant synthesis, secretion, and metabolism is critical for air breathing and, ultimately, survival. The goal of this review is to summarize our current understanding and highlight important knowledge gaps in surfactant homeostatic mechanisms.
A Mathematical Analysis of the Card Game of Betweenies through Kelly′s Criterion
Authors: Drakakis Konstantinos
Published: June 2010

In the game of Betweenies, the player is dealt two cards out of a deck and bets on the probability that the third card to be dealt will have a numerical value in between the values of the first two cards. In this work, we
present the exact rules of the two main versions of the game, and we study the optimal betting strategies. After
discussing the shortcomings of the direct approach, we introduce an information‐theoretic technique, Kelly′s
criterion, which basically maximizes the expected log‐return of the bet: we offer an overview, discuss feasibility
issues, and analyze the strategies it suggests. We also provide some gameplay simulations.
The Combination of a Histone Deacetylase Inhibitor with the Bcl-2 Homology Domain-3 Mimetic GX15-070 Has Synergistic Antileukemia Activity by Activating Both Apoptosis and Autophagy
Authors: Wei Yue , Kadia Tapan , Tong Weigang , Zhang Ming , Jia Yu , Yang Hui , Hu Yumin , Tambaro Francesco Paolo , Viallet Jean , O'Brien Susan , Garcia-Manero Guillermo
Published: June 2010

Purpose: Single-agent histone deacetylase inhibitors (HDACi) have limited clinical activity in human leukemia. Although the way HDACi exert their antileukemia effect is not fully understood, it is accepted that induction of apoptosis is important. We hypothesized, therefore, that combination of an HDACi with a proapoptotic agent, such as the Bcl-2 homology domain-3 mimetic GX15-070, could result in enhanced antileukemia activity.

Experimental Design: We analyzed the cellular and molecular effects of two different HDACi (MGCD0103 and vorinostat) in combination with GX15-070 in leukemia cell lines and primary acute myelogenous leukemia cells.

Results: We showed that the combination had synergistic antileukemia effect both in leukemia cell lines and in primary acute myelogenous leukemia cells. Using molecular markers and electron microscopy, we observed that in addition to apoptosis, autophagy accounts for the nonapoptotic decrease in cell viability, an effect that could be inhibited by chloroquine, an inhibitor of autophagy. Finally, we established a role for calpain activity in the induction of both autophagy and apoptosis by this combination.

Conclusions: The combination of an HDACi and GX15-070 has synergistic antileukemia activity, and the effect is mediated by induction of apoptosis and autophagy. The combination should be studied in clinical trials of leukemia and the role of autophagy in leukemia therapy needs to be better understood. Clin Cancer Res; 16(15); 3923–32. ©2010 AACR.
PIKing the Right Patient
Authors: Turke Alexa B. , Engelman Jeffrey A.
Published: June 2010

HER2 amplification and PIK3CA mutation were validated as biomarkers for sensitivity to the single-agent phosphoinositide 3-kinase (PI3K) inhibitor, GDC-0941, in breast cancer models. A novel expression profile was developed to identify other breast cancers sensitive to PI3K inhibitors. These expression studies highlighted feedback networks connecting TORC1, PI3K, and mitogen-activated protein kinase (MAPK) pathways, and underscored the potential for combination therapies. Clin Cancer Res; 16(14); 3523–5. ©2010 AACR.
Coupling Vascular and Myocardial Inflammatory Injury into a Common Phenotype of Cardiovascular Dysfunction: Systemic Inflammation and Aging – A Mini-Review
Authors: Puntmann Valentina O. , Taylor Peter C. , Mayr Manuel
Published: June 2010

The rising epidemic of cardiovascular (CV) disease is fuelled by obesity, hypertension and diabetes and, independently and cumulatively, by an aging population. Extensive research identified immunoinflammatory mechanisms as key drivers in the initiation and progression of the disease, from early asymptomatic stages of vascular and myocardial injury leading to the clinically manifest dysfunction and remodeling in advanced stages. Underlying processes include endothelial dysfunction and extracellular matrix restructuration leading to increased vascular stiffness, as well as myocardial remodeling with dilatation and wall thinning. In this, overproduction of tumor necrosis factor-α, amongst others, contributes to generalized CV injury and dysfunction. Moreover, recent insights into the involvement of innate and adaptive immunity in atherosclerosis have shed light on many interesting parallels with chronic systemic inflammatory conditions, such as rheumatoid arthritis, with aggravated inflammation-induced vascular and myocardial injury. Besides, chronologic age has been identified as a potent, independent risk for reduced CV capacity and a plethora of heart diseases, with other modifiable risk factors acting as accelerators. We discuss the available evidence and propose that characterization of inflammatory CV responses might reveal a distinctive CV inflammatory phenotype. A comprehensive noninvasive bio-signature, comprising immunomic biomarkers and integrated noninvasive imaging, may serve as a potential tool in the early diagnosis and prognostication of CV risk.
Human Vascular Smooth Muscle Cells Lack Essential Costimulatory Molecules to Activate Allogeneic Memory T Cells
Authors: Zhang Pei , Manes Thomas D. , Pober Jordan S. , Tellides George
Published: June 2010

Objective—

The arterial media, populated by vascular smooth muscle cells (VSMC), is an immunoprivileged compartment and, in contrast to the intima or adventitia containing endothelial cells, is generally spared by inflammatory processes, such as arteriosclerosis. To determine mechanisms of medial immunoprivilege, we investigated the ability of human VSMC versus endothelial cells to activate allogeneic T cells in vitro.

Methods and Results—

Unlike cultured endothelial cells, cultured VSMC do not activate allogeneic memory CD4 or CD8 T cells and fail to effectively support T-cell proliferation to the polyclonal activator, phytohemagglutinin, consistent with a defect in costimulation function. Although many costimulators are comparably expressed on both cell types, endothelial cells but not VSMC basally express OX40 ligand and upregulate inducible costimulator ligand in response to proinflammatory cytokines. OX40 ligand-transduced, but not control- or inducible costimulator ligand-transduced, VSMC acquire the capacity to stimulate allogeneic memory CD4 T cells to produce cytokines and to proliferate in the presence of supplemental
l
-tryptophan. OX40 ligand overexpression, although not essential, also enhances allogeneic memory CD8 T-cell responses to VSMC after
l
-tryptophan supplementation.

Conclusion—

The inability of cultured VSMC to activate memory T cells results from a lack of essential costimulators, particularly OX40 ligand, in addition to indoleamine 2,3-dioxygenase-mediated tryptophan depletion.