bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbene‐Stabilized Phosphenium Oxides and Sulfides
Authors: Maaliki Carine , Lepetit Christine , Duhayon Carine , Canac Yves , Chauvin Remi
Published: October 2012

Carbene→chalcogenophosphenium adducts, which correspond to an intermolecular stabilization mode of the so far elusive, free oxo‐ and thiooxophosphenium species [R2P+=X] (X=O, S) by imidazolylidene (NHC) and diaminocyclopropenylidene (BAC) donors, have been isolated and fully characterized. The dative character of the R2C:→P+(X)Ph2 bond was confirmed experimentally by nucleophilic displacement of the carbene donor with a chloride ion and by an exchange reaction of the NHC ligand of the NHC:→P+(O)Ph2 adduct with an independently prepared BAC ligand, thereby giving the BAC:→P+(O)Ph2 adduct. This dative character was further characterized by the DFT‐calculated preference of carbene→chalcogenophosphenium systems for a heterolytic dissociation mode over a homolytic one.
Dipole Field Guided Orientated Attachment of Nanocrystals to Twin‐Brush ZnO Mesocrystals
Authors: Liu Ming‐Han , Tseng Yao‐Hung , Greer Heather F. , Zhou Wuzong , Mou Chung‐Yuan
Published: October 2012

Mesocrystals of ZnO were synthesized hydrothermally by using gum arabic as a structure‐directing agent. Their hierarchical structure has a unique twin‐brush form consisting of vertically aligned nanorods in a single‐crystal‐like porous form. The formation mechanism of the twin‐brush ZnO was investigated by quenching a series of samples at different times and examining them by TEM, SEM, and XRD. The alignment of ZnO crystal units can be modulated by adding simple salts such as KCl to change the units from nanorods to nanoplates. This can be explained by screening the dipolar force of the polar crystal. Local cathodoluminescence of twin‐brush ZnO was used to follow the local structure changes.
Singlet Oxygen Photo‐Oxygenation in Water/Pluronic F‐127 Hydrogels: Increased Reaction Efficiency Coupled with a Switch in Regioselectivity
Authors: Griesbeck Axel G. , Uhlig Johannes , Sottmann Thomas , Belkoura Lhoussaine , Strey Reinhard
Published: October 2012

Pluronic F‐127 hydrogels are highly efficient microenvironments for photochemical reactions, as demonstrated for singlet oxygen reactions of monoalkenes. Nonpolar substrates are localized in the nanosized polymer compartment, which can be visualized by neutron scattering. The efficiency of 1O2 reactions is strongly increased for tiglate derivatives and the regioselectivity of the ene reaction of trisubstituted alkenes is completely switched in comparison with solution phase and inverted in comparison with intrazeolite photo‐oxygenations.
A Biomimetic Pathway for Vanadium‐Catalyzed Aerobic Oxidation of Alcohols: Evidence for a Base‐Assisted Dehydrogenation Mechanism
Authors: Wigington Bethany N. , Drummond Michael L. , Cundari Thomas R. , Thorn David L. , Hanson Susan K. , Scott Susannah L.
Published: October 2012

The first step in the catalytic oxidation of alcohols by molecular O2, mediated by homogeneous vanadium(V) complexes [LVV(O)(OR)], is ligand exchange. The unusual mechanism of the subsequent intramolecular oxidation of benzyl alcoholate ligands in the 8‐hydroxyquinolinato (HQ) complexes [(HQ)2VV(O)(OCH2C6H4‐p‐X)] involves intermolecular deprotonation. In the presence of triethylamine, complex 3 (X=H) reacts within an hour at room temperature to generate, quantitatively, [(HQ)2VIV(O)], benzaldehyde (0.5 equivalents), and benzyl alcohol (0.5 equivalents). The base plays a key role in the reaction: in its absence, less than 12 % conversion was observed after 72 hours. The reaction is first order in both 3 and NEt3, with activation parameters ΔH≠=(28±4) kJ mol−1 and ΔS≠=(−169±4) J K−1 mol−1. A large kinetic isotope effect, 10.2±0.6, was observed when the benzylic hydrogen atoms were replaced by deuterium atoms. The effect of the para substituent of the benzyl alcoholate ligand on the reaction rate was investigated using a Hammett plot, which was constructed using σp. From the slope of the Hammett plot, ρ=+(1.34±0.18), a significant buildup of negative charge on the benzylic carbon atom in the transition state is inferred. These experimental findings, in combination with computational studies, support an unusual bimolecular pathway for the intramolecular redox reaction, in which the rate‐limiting step is deprotonation at the benzylic position. This mechanism, that is, base‐assisted dehydrogenation (BAD), represents a biomimetic pathway for transition‐metal‐mediated alcohol oxidations, differing from the previously identified hydride‐transfer and radical pathways. It suggests a new way to enhance the activity and selectivity of vanadium catalysts in a wide range of redox reactions, through control of the outer coordination sphere.
ChemInform Abstract: Nd4.67Ru3Mg8.83 — A Magnesium‐Rich Compound with Ru@Mg4Nd4 Square Antiprisms and Mg@Mg8 Cubes as Basic Building Units.
Authors: Linsinger Stefan , Rodewald Ute Ch. , Poettgen Rainer
Published: October 2012

The Mg‐rich title compound is prepared from the elements (Ta ampule, 1473 K, 8 h followed by annealing at 673 K for 96 h) and characterized by powder and single crystal XRD.
ChemInform Abstract: Sulfides with Strong Nonlinear Optical Activity and Thermochromism: ACd4Ga5S12 (A: K, Rb, Cs).
Authors: Lin Hua , Zhou Liu‐Jiang , Chen Ling
Published: October 2012

The title compounds are prepared in high yields by reaction of Cd, Ga, and S in a molar ratio of 4:5:12 and a slight excess of MCl (M: K, Rb, Cs) as reactive flux (1273 K, 7 d).
ChemInform Abstract: Origin of the Room‐Temperature Ferromagnetism in Sr3YCo4O10+δ (0.5 < δ < 1.0): Formation of Ferromagnetic Spin Bags in the Oxygen‐Rich Perovskite Layers.
Authors: Bettis Jerry L. Jr. , Xiang Hongjun , Whangbo Myung‐Hwan
Published: October 2012

The title compound is characterized by DFT electronic structure calculations.
ChemInform Abstract: New Iron‐Based Mixed‐Polyanion Cathodes for Lithium and Sodium Rechargeable Batteries: Combined First Principles Calculations and Experimental Study.
Authors: Kang Kisuk , et al. et al.
Published: October 2012

Compounds (III) and (VI) crystallize in the orthorhombic space group Pn21a (powder XRD and neutron diffraction) and contain three‐dimensional Na/Li paths supported by P2O7 pillars in the crystal.
ChemInform Abstract: (C8H22N4Zn) 2Ge7O14(OH)F3: A One‐Dimensional Zinc Germanate Containing Hollow Columns with an 18‐Membered Window.
Authors: Nguyen Quang Bac , Li Kwang‐Hwa
Published: October 2012

Title compound (III) is characterized by single crystal XRD, solid state 19F NMR, and IR spectroscopy.
ChemInform Abstract: Nitrate‐Bridged “Pseudo‐Double‐Propeller”‐Type Lanthanide(III)—Copper(II) Heterometallic Clusters: Syntheses, Structures, and Magnetic Properties.
Authors: Chaudhari Abhijeet K. , Joarder Biplab , Riviere Eric , Rogez Guillaume , Ghosh Sujit K.
Published: October 2012

Compounds (III) are characterized by single crystal XRD and magnetic measurements.
ChemInform Abstract: Asymmetric Catalytic Alkynylation of Acetaldehyde: Application to the Synthesis of (+)‐Tetrahydropyrenophorol.
Authors: Trost Barry M. , Quintard Adrien
Published: October 2012

The simple title process is applied to the rapid and efficient synthesis of the natural title compound (X).
ChemInform Abstract: A Convenient Conversion of Substituted Cyclohexenones into Aryl Methyl Ketones.
Authors: Gehring Andre P. , Bracher Franz
Published: October 2012

With a view to preparing biologically active alkaloid systems of type (III)/(IV), a suitable method for the introduction of a methyl ketone segment to the cyclohexenone part is required.
ChemInform Abstract: Rapid Preparation of Cycloheptane Ring from 1,2‐Diketone and Bis(iodozincio)methane via Oxy‐Cope Rearrangement Using Microflow System.
Authors: Haraguchi Ryosuke , Takada Yoshiaki , Matsubara Seijiro
Published: October 2012

The title reaction is studied as both classical one‐pot reaction and in a microflow system.
ChemInform Abstract: Nucleophilic Pentafluorophenylation of Nitroalkenes.
Authors: Kondratyev Nikolay S. , Zemtsov Artem A. , Levin Vitalij V. , Dilman Alexander D. , Struchkova Marina I.
Published: October 2012

Optimized conditions A) have to be changed in the case of aliphatic nitro compounds.
ChemInform Abstract: Copper‐Catalyzed Cross‐Coupling of O‐Alkyl Hydroxamates with Aryl Iodides.
Authors: Kukosha Tatyana , Trufilkina Nadezhda , Belyakov Sergey , Katkevics Martins
Published: October 2012

No reaction is observed with aryl bromides or chlorides.
ChemInform Abstract: Nano‐TiO2: An Efficient and Reusable Heterogeneous Catalyst for Ring Opening of Epoxides under Solvent‐Free Conditions.
Authors: Chen Xi'an , Wu Huayue , Wang Shun , Huang Shaoming
Published: October 2012

The reaction is remarkably stereo‐ and regioselective and the catalytic activity of titanium dioxide strongly depends on particle size and surface area.
ChemInform Abstract: Biomimetic Flavin‐Catalyzed Aldehyde Oxidation.
Authors: Murray Alexander T. , Matton Pascal , Fairhurst Nathan W. G. , John Matthew P. , Carbery David R.
Published: October 2012

The presence of a strong electron‐donating group in the ortho‐ or para‐position [cf.(IIb) and (IId)] leads to formation of phenol by‐products, consistent with a competitive Dakin oxidation.
ChemInform Abstract: Palladium‐Catalyzed N‐Monoarylation of Amidines and a One‐Pot Synthesis of Quinazoline Derivatives.
Authors: McGowan Meredeth A. , McAvoy Camille Z. , Buchwald Stephen L.
Published: October 2012

The particle size of Cs2CO3 is crucial: whereas the commercial product causes no reaction or very low yields, the finely grounded substance proves to be successful.
ChemInform Abstract: Free Porphyrin Catalyzed Direct C—H Arylation of Benzene with Aryl Halides.
Authors: Ng Yeuk Sze , Chan Chung Sum , Chan Kin Shing
Published: October 2012

The process can be carried under nitrogen or air without any difference.
ChemInform Abstract: Synthesis and Properties of Novel i‐ and g‐Line Sensitive Photoacid Generators Based on 9‐Fluorenone Derivatives with Aryl—Ethynyl Units.
Authors: Kodama Shintaro , Okamura Haruyuki , Shirai Masamitsu
Published: October 2012

This is the first example of a photoacid generator (PAG) synthesis via the introduction of arylethynyl units into the chromophore.
ChemInform Abstract: Efficient AgOTf or Ph3PAuCl—AgSbF6 Catalyzed Cyclization of 1‐Hydroxy‐2‐alkynylallylphosphonates/2‐alkynylallyl Alcohols to 2‐Furylphosphonates/2,3,5‐Trisubstituted Furans.
Authors: Kotikalapudi Ramesh , Swamy K. C. Kumara
Published: October 2012

Optimized reaction conditions are developed for the cyclization of 2‐alkynylallyl alcohols to give highly substituted furanone derivatives.
ChemInform Abstract: A Convenient Access to γ‐Lactones from O‐Allyl‐α‐Bromoesters Using a One‐Pot Ionic—Radical—Ionic Sequence.
Authors: Beneteau Romain , Lebreton Jacques , Denes Fabrice
Published: October 2012

In continuation of recently published studies on the cyclization of in situ generated α‐bromo aluminum acetals, an efficient protocol for preparation of γ‐lactones is presented.
ChemInform Abstract: A Novel Convergent Method for the Synthesis of α‐Acyl‐γ‐hydroxylactams and Its Application in the Total Synthesis of PI‐090 and 091.
Authors: Uchiro Hiromi , Shionozaki Nobuhiro , Kobayakawa Yu , Nakagawa Hiroko , Makino Kimiko
Published: October 2012

The aldol reaction of N‐Boc‐protected γ‐hydroxylactams (I) provides access towards title α‐acyl‐γ‐hydroxylactams (III).
ChemInform Abstract: Synthesis, Cytotoxic Properties and Tubulin Polymerization Inhibitory Activity of Novel 2‐Pyrazoline Derivatives.
Authors: Abdel‐Aziz Mohamed , Aly Omar M. , Khan Sabine S. , Mukherjee Kamalika , Bane Susan
Published: October 2012

A series of novel 3,5‐diarylpyrazoline derivatives (III) are synthesized and screened for their anticancer activity in a tubulin polymerization inhibitory assay.
ChemInform Abstract: Regioselective Synthesis and Antimicrobial Studies of Ester Linked 1,4‐Disubstituted 1,2,3‐Bistriazoles.
Authors: Lal Kashmiri , Kumar Ashwani , Pavan M. S. , Kaushik C. P.
Published: October 2012

The title compounds (III) are synthesized via click chemistry by Cu‐catalyzed cycloaddition of various bisalkynes with azides.
ChemInform Abstract: Hypervalent Iodine(V) Mediated Mild and Convenient Synthesis of Substituted 2‐Amino‐1,3,4‐oxadiazoles.
Authors: Prabhu Girish , Sureshbabu V. V.
Published: October 2012

A convenient one‐pot two‐step sequence allows the synthesis of the title compounds (III) by reaction of acylhydrazides with isothiocyanates and subsequent IBX‐mediated cyclodesulfurization of the resulting intermediate acylthiosemicarbazides.
ChemInform Abstract: An Improved Microwave Assisted One‐Pot Synthesis, and Biological Investigations of Some Novel Aryldiazenyl Chromeno Fused Pyrrolidines.
Authors: Parmar Narsidas J. , Pansuriya Bhavesh R. , Barad Hitesh A. , Kant Rajni , Gupta Vivek K.
Published: October 2012

An improved method for the synthesis of aryl diazenylchromenopyrrolidines is presented by means of intramolecular 1,3‐dipolar cycloaddition of azamethine ylide from the new aldehyde substrate (I).
ChemInform Abstract: Rh(II)‐Cp*—TsDPEN Catalyzed Aqueous Asymmetric Transfer Hydrogenation of Chromenones into Saturated Alcohol: C=C and C=O Reduction in One Step.
Authors: Tang Lei , Lin Zechao , Wang Qiwei , Wang Xiaobei , Cun Linfeng , Yuan Weicheng , Zhu Jin , Deng Jingen
Published: October 2012

The title rhodium TsDPEN complex efficiently catalyzes the asymmetric transfer hydrogenation of chromenones to produce alcohols (II) with excellent enantioselectivities.
ChemInform Abstract: Selective Trifluoromethylation and Alkynylation of Tetrahydroisoquinolines Using Visible Light Irradiation by Rose Bengal.
Authors: Fu Weijun , Guo Wenbo , Zou Guanglong , Xu Chen
Published: October 2012

A convenient method for oxidative coupling of tetrahydroisoquinoline derivatives (I) with trimethyl(trifluoromethyl)silane (II) and terminal alkynes (IV) via selective C—H activation is described.
ChemInform Abstract: Triphenyl Verdazyl Radicals′ Reactivity with Alkyne Carboxylates as a Synthetic Route to 1‐(Phenyldiazenyl)isoquinoline‐3,4‐dicarboxylates.
Authors: Bancerz Matthew , Prack Ernest , Georges Michael K.
Published: October 2012

Only one isoquinoline product is formed if the starting radical bears either a C‐phenyl or an aryl with ortho‐ or para‐substituent.
ChemInform Abstract: Multi‐Component Solvent‐Free versus Stepwise Solvent Mediated Reactions: Regiospecific Formation of 6‐Trifluoromethyl and 4‐Trifluoromethyl‐1H‐pyrazolo[3,4‐b]pyridines.
Authors: Aggarwal Ranjana , Kumar Virender , Bansal Anshul , Sanz Dionisia , Claramunt Rosa M.
Published: October 2012

The regiospecific synthesis of 6‐fluoromethyl‐pyrazolopyridines (IV) is achieved in high yields via a three‐component reaction under solvent‐free conditions.
ChemInform Abstract: Steroids from Commiphora mukul Display Antiproliferative Effect Against Human Prostate Cancer PC3 Cells via Induction of Apoptosis.
Authors: Shen Tao , Zhang Li , Wang Yan‐Yan , Fan Pei‐Hong , Wang Xiao‐Ning , Lin Zhao‐Min , Lou Hong‐Xiang
Published: October 2012

isolation, structure elucidation and anticancer activity of two new stigmastane‐type steroids (Ia) and (Ib)
ChemInform Abstract: Synthesis of Novel α‐Amino Acid Functionalized 6‐Fluoro Quinolones, Their Antibacterial Activity and Molecular Docking Studies.
Authors: Rao P. Shanthan , et al. et al.
Published: October 2012

Among the novel α‐amino acid functionalized fluoroquinolones, derivative (Ie) is found to be the most active compound.
ChemInform Abstract: Binary and Ternary Atomic Layers Built from Carbon, Boron, and Nitrogen
Authors: Ajayan Pulickel M. , et al. et al.
Published: October 2012

Review: 182 refs.
ChemInform Abstract: Recent Trends in the Synthesis of Carbazoles: An Update
Authors: Roy Joyeeta , Jana Amit Kumar , Mal Dipakranjan
Published: October 2012

Review: 82 refs.
ChemInform Abstract: Aryne Intermediates in the Synthesis of Polynuclear Heterocyclic Systems
Authors: Kovalev I. S. , Kopchuk D. S. , Zyryanov G. V. , Slepukhin P. A. , Rusinov V. L. , Chupakhin O. N.
Published: October 2012

Review: 57 refs.
ChemInform Abstract: Hybrid Nanostructures for Energy Storage Applications
Authors: Reddy Arava Leela Mohana , Gowda Sanketh R. , Shaijumon Manikoth M. , Ajayan Pulickel M.
Published: October 2012

Review: 208 refs.
ChemInform Abstract: Reforming of Biogas Using Electrochemical Cell
Authors: Hirata Yoshihiro , Matsunaga Naoki , Saneshima Soichiro
Published: October 2012

Review: 34 refs.
Robust location estimation with missing data
Authors: Sued Mariela , Yohai Victor J.
Published: October 2012

In a missing data setting, we have a sample in which a vector of explanatory variables ${\bf x}_i$ is observed for every subject i, while scalar responses $y_i$ are missing by happenstance on some individuals. In this work we propose robust estimators of the distribution of the responses assuming missing at random (MAR) data, under a semiparametric regression model. Our approach allows the consistent estimation of any weakly continuous functional of the response's distribution. In particular, strongly consistent estimators of any continuous location functional, such as the median, L‐functionals and M‐functionals, are proposed. A robust fit for the regression model combined with the robust properties of the location functional gives rise to a robust recipe for estimating the location parameter. Robustness is quantified through the breakdown point of the proposed procedure. The asymptotic distribution of the location estimators is also derived. The proofs of the theorems are presented in Supplementary Material available online. The Canadian Journal of Statistics 41: 111–132; 2013 © 2012 Statistical Society of Canada
The Interpersonal Circle and the Interpersonal Octagon: A Confluence of Ideas
Authors: Birtchnell John
Published: October 2012

This paper compares and contrasts the underlying principles of two conceptual systems—the interpersonal circle and the interpersonal octagon—for classifying and measuring a person's interpersonal tendencies. Both systems have been represented by two intersecting axes: a horizontal one extending from close/warm involvement to distant/cold separation and a vertical one extending from upper/control to lower/submission. In both systems, intermediate axes have been inserted between these two main ones. Where the circle would appear to be concerned with traits, the octagon is concerned with what have been termed states of relatedness. The two systems differ in their explanation and definition of adaptive and maladaptive relating behaviour. Whereas the circle has been closely aligned with the establishment of a bipolar relationship between the poles of the axes and with the mathematical model that is called the circumplex, the octagon has not. The most widely used circle‐based measure is the circumplex version of the Inventory of Interpersonal Problems. It generates high positive correlations between scales and a large, first general factor, but these imperfections have been corrected by the statistical procedure called ipsatization. The principal octagon‐based measure is the Person's Relating to Others Questionnaire. A number of high positive correlations have been demonstrated between the scales of the Inventory of Interpersonal Problems and the corresponding scales of the Person's Relating to Others Questionnaire. Therefore, despite there being differences in the underlying theories, the two questionnaires would appear to be measuring similar constructs. Copyright © 2012 John Wiley & Sons, Ltd.

Key Practitioner Message:

The interpersonal circle and the interpersonal octagon are two separate theoretical systems for representing a person's relating tendencies.

Both systems are constructed around a horizontal, close‐distant axis and a vertical, upper‐lower axis.

Both systems acknowledge that relating can be either adaptive or maladaptive, but where the circle incorporates both adaptive and maladaptive forms of relating within the same theoretical structure, there is a separate, adaptive (positive) octagon and and a separate, maladaptive (negative) octagon.

Both systems have a questionnaire for the measurement of a person's general relating tendencies, but the octagon-based questionnaire is designed specifically to measure maladaptive (negative) relating.

Interrelating concerns the relating that occurs between two specified individuals. Questionnaires have been developed by which each individual can record how, within the framework of the octagon, s/he relates (negatively) to the other and how s/he considers that the other relates (negatively) to her/him. There is no interrelating measure that is based upon the circle.
Application of Steroid Hormone Metabolomics in Search of Biomarkers in Clinical Research
Authors: Kotłowska Alicja
Published: October 2012

Preclinical Research

Metabolomics is a discipline that concentrates on the global assessment of endogenous metabolites present in a biological system. Metabolic profiling has been applied to cells, tissues, and/or biofluids in order to evaluate disease progress, broaden the understanding of the disorder, and to select potential biomarkers. Steroid hormones play an important role in the regulation of routine functions in the human body, and their measurement in biological samples is essential for the diagnosis of various endocrine disorders. The present overview describes various strategies and analytical techniques applied in metabolomic studies, particularly with reference to the steroid metabolic profiling useful for the search of novel biomarkers.
Integrating the NCI‐60 Data with “Omics” for Drug Discovery
Authors: Burkard Mark E.
Published: October 2012

Preclinical Research

The National Cancer Institute (NCI)‐60 screening panel represents one of the largest chemical cell line screening endeavors ever undertaken. This screen, starting in the early 1990s, has evaluated the effect of ∼400,000 compounds on the growth of a panel of over 60 human cancer cell lines. The screen and the extensive characterization of the cell lines provide a wealth of data on determinants of drug sensitivity, much of it publicly available. Here, an overview of the data is provided including basic characteristics of cell lines, the variance of 50% growth inhibitory concentration of over 40,000 chemicals, and expression of 17,775 genes across these cell lines. This analysis revealed that only a fraction of compounds have differential sensitivities across lines. For the majority of compounds, the genomic underpinnings of drug sensitivity cannot possibly be discerned from the data as there is no significant variance between cell lines. This limitation applies, surprisingly, to platinum agents and even to tamoxifen, demonstrating the limitation of this screening methodology to capture all differences that predict drug sensitivity in the context of human cancer. In contrast, methotrexate has remarkably disparate effects across cell lines, suggesting that the origin of its sensitivity can be discerned. Correlations of drug sensitivity and gene expression reveal some remarkably robust correlations across the NCI‐60 cell lines, suggesting their value as predictive biomarkers, or perhaps even drug targets. These results demonstrate both the power and limitations of NCI‐60 type screens to identify the determinants of drug sensitivity.
Interrogating Novel Areas of Chemical Space for Drug Discovery using Chemoinformatics
Authors: Medina‐Franco José L.
Published: October 2012

Preclinical Research

Chemoinformatic approaches have an essential role in the systematic description and visualization of the chemical space for drug discovery projects. These methods enable the quantitative comparison of general screening collections and the systematic classification of approved drugs and databases annotated with biological activity to define biologically and medicinally relevant chemical spaces. Profiling of chemical diversity, molecular complexity, and physicochemical properties of compound libraries using chemoinformatic approaches provide a solid basis to generate hypothesis of how to interrogate novel areas of chemical space for enhanced drug discovery. This commentary is focused on the application of chemoinformatic approaches to mine, and to navigate the chemical space of compound collections. The discussion is centered on the concept of chemical space, types of compound libraries used in drug discovery programs, applications of chemical space mining and visualization using chemoinformatic methods, and strategies to expand the pharmaceutical relevant chemical space with emphasis on the notion of molecular complexity.
Challenges for the Application and Development of Omics Health Technologies in Developing Countries
Authors: Huzair Farah , Borda‐Rodriguez Alexander
Published: October 2012

Preclinical Research

Omics technologies and particular applications for diagnostics and pharmacogenomics, can potentially identify disease risk, reduce disease burden, and provide better and more cost‐effective health care. International institutions have recognized that global justice necessitates equity of access to medical technologies for developing and well as developed countries. The promise of the omics technologies may remain unfulfilled for developing countries unless capacities for exploitation and integration are created. These capacities are those that enable contribution efforts to upstream data collection and innovation, and downstream governance and regulation.
Residual beta cell function at diagnosis of type 1 diabetes in children and adolescents varies with gender and season
Authors: Samuelsson U. , Lindblad B. , Carlsson A. , Forsander G. , Ivarsson S. , Kockum I. , Lernmark Å. , Marcus C. , Ludvigsson J. ,   Better Diabetes Diagnosis (BDD) study group
Published: October 2012

Background

There are seasonal variations and gender differences in incidence of type 1 diabetes (T1D), metabolic control and responses to immune interventions at onset of the disease.

We hypothesized that there are seasonal and gender differences in residual insulin secretion already at diagnosis of T1D.

Methods

In 2005, a national study, the Better Diabetes Diagnosis, was started to classify all newly diagnosed children and adolescents with diabetes. About 95% (3824/4017) of the patients were classified as T1D, and our analyses are based on the patients with T1D.

Results

C‐peptide was lower in younger children, 0–10 years of age (0.23 ± 0.20 nmol/L) than in older children, 11–18 years of age (0.34 ± 0.28 nmol/L) (p < 0.000 ). There was a seasonal variation in non‐fasting serum C‐peptide, significantly correlated to the seasonal variation of diagnosis (p < 0.01). Most children were diagnosed in January, February and March as well as in October when C‐peptide was highest, whereas fewer patients were diagnosed in April and May when serum C‐peptide was significantly lower (p < 0.01). The seasonal variation of C‐peptide was more pronounced in boys than in girls (p < 0.000 and p < 0.01, respectively). Girls had higher C‐peptide than boys (p < 0.05), especially in early puberty.

Conclusions

Both seasonal and gender differences in residual beta cell function exist already at diagnosis of T1D. These observations have consequences for treatment and for randomizing patients in immune intervention clinical trials. Copyright © 2012 John Wiley & Sons, Ltd.
Biofeedback can reduce foot pressure to a safe level and without causing new at‐risk zones in patients with diabetes and peripheral neuropathy
Authors: De León Rodriguez D. , Allet L. , Golay A. , Philippe J. , Assal J.‐Ph. , Hauert C.‐A. , Pataky Z.
Published: October 2012

Background

Plantar pressure reduction is mandatory for diabetic foot ulcer healing. Our aim was to evaluate the impact of a new walking strategy learned by biofeedback on plantar pressure distribution under both feet in patients with diabetic peripheral neuropathy.

Methods

Terminally augmented biofeedback has been used for foot off‐loading training in 21 patients with diabetic peripheral sensory neuropathy. The biofeedback technique was based on a subjective estimation of performance and objective visual feedback following walking sequences. The patient was considered to have learned a new walking strategy as soon as the peak plantar pressure (PPP) under the previously defined at‐risk zone was within a range of 40–80% of baseline PPP in 70% of the totality of steps and during three consecutive walking sequences. The PPP was measured by a portable in‐shoe foot pressure measurement system (PEDAR®) at baseline (T0), directly after learning (T1) and at 10‐day retention test (T2).

Results

The PPP under at‐risk zones decreased significantly at T1 (165 ± 9 kPa, p < 0.0001) and T2 (167 ± 11, p = 0.001), as compared with T0 (242 ± 12 kPa) without any increase of the PPP elsewhere.

At the contralateral foot (not concerned by off‐loading), the PPP was slightly higher under the lateral midfoot at T1 (68 ± 8 kPa, p = 0.01) and T2 (65 ± 8 kPa, p = 0.01), as compared with T0 (58 ± 6 kPa).

Conclusions

The foot off‐loading by biofeedback leads to a safe and regular plantar pressure distribution without inducing any new ‘at‐risk’ area under both feet. Copyright © 2012 John Wiley & Sons, Ltd.
HVC lesions modify immediate early gene expression in auditory forebrain regions of femalesongbirds
Authors: Lynch Kathleen S. , Kleitz‐Nelson Hayley K. , Ball Gregory F.
Published: October 2012

It is well established that auditory forebrain regions of oscine birds are essential for the encoding of species‐typical songs and are, therefore, vital for recognition of song during sociosexual interactions. Regions such as the caudal medial nidopallium (NCM) and the caudal medial mesopallium (CMM) are involved in perceptual processing of song and the formation of auditory memories. There is an additional telencephalic nucleus, however, that has also been implicated in species recognition. This nucleus is HVC, a prominent nucleus that sits at the apex of the song system, and is well known for its critical role in song learning and song production in male songbirds. Here, we explore the functional relationship between auditory forebrain regions (i.e., NCM and CMM) and HVC in female canaries (Serinus canaria). We lesion HVC and examine immediate early gene responses to conspecific song presentation within CMM and NCM to explore whether HVC can modulate auditory responses within these forebrain regions. Our results reveal robust deficits in ZENK‐ir in CMM and NCM of HVC‐lesioned females when compared with control‐ and sham‐lesioned females, indicating that functional connections exists between HVC and NCM/CMM. Although these connected regions have been implicated in song learning and production in males, they likely serve distinct functions in female songbirds that face the task of song recognition rather than song production. Identifying functional connections between HVC and auditory regions involved in song perception is an essential step toward developing a comprehensive understanding of the neural basis of song recognition. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013
Implementing a dynamic riparian vegetation model in three European river systems
Authors: García‐Arias A. , Francés F. , Ferreira T. , Egger G. , Martínez‐Capel F. , Garófano‐Gómez V. , Andrés‐Doménech I. , Politti E. , Rivaes R. , Rodríguez‐González P. M.
Published: October 2012

Riparian ecosystems are required to be preserved to achieve a good ecological status. The Water Framework Directive (2000/60/EC) specifically supports the assessment of new management tools that allow the European Member States to achieve good ecological status of river‐related ecosystems. Within several approaches, a dynamic riparian vegetation distributed model (CASiMiR‐vegetation), with a time step of 1 year, has been selected as a useful first‐step tool to achieve the Water Framework Directive requirements. The model has been implemented into three river reaches with different climatic and hydrologic settings, located in three European countries. Common bases were established in the model setup. The model was calibrated independently in the Kleblach reach (Drau River, Austria), the Ribeira reach (Odelouca River, Portugal), and the Terde reach (Mijares River, Spain) with simulation periods of 8, 11 and 41 years, respectively. The parameter values and the results were comparable between the different countries. The calibration performance achieved high correctly classified instances (60%). Additionally, weighted kappa values ranged from 0·52 to 0·66 in distinguishing riparian succession phases. The model behaved similarly in the validation, even offering better results in most cases. This work demonstrates the applicability of this model in the simulation of the riparian vegetation dynamic distribution over a wide range of environments. As it performs in a robust manner and with good results in reaches with different hydrological characteristics, the model could be also applied to analyse different hydrological scenarios or to predict changes after restoration measures within a reach. Copyright © 2012 John Wiley & Sons, Ltd.
Simvastatin inhibits secretion of Th17‐polarizing cytokines and antigen presentation by DCs in patients with relapsing remitting multiple sclerosis
Authors: Zhang Xin , Tao Yazhong , Wang Jinzhao , Garcia‐Mata Rafael , Markovic‐Plese Silva
Published: October 2012

Statins, widely used cholesterol‐lowering agents, have also been demonstrated to have antiinflammatory effects. Here, we characterize the capacity of simvastatin to target DCs and modulate T‐cell priming and Th17‐cell differentiation, in a cohort of patients with relapsing remitting multiple sclerosis (RRMS). We report that simvastatin inhibits IL‐1β, IL‐23, TGF‐β, IL‐21, IL‐12p70, and induces IL‐27 secretion from DCs in RRMS patients, providing an inhibitory cytokine milieu for Th17 and Th1‐cell differentiation. The effect on DCs is mediated via induction of SOCS1, SOCS3, and SOCS7 gene expression, which are associated with the inhibition of STAT1, STAT3, and ERK1/2 phosphorylation. A geranylgeranyl transferase inhibitor replicated simvastatin's effects on DC cytokine secretion, implicating that simvastatin‐induced depletion of isoprenoids mediates this effect. Simvastatin inhibited antigen presentation by DCs via suppression of the MHC class I expression, costimulatory molecules CD80 and CD40, and by inducing a dramatic loss of dendritic processes. The changes in DC morphology were also mediated via inhibition of geranylgeranylation. The therapeutic use of geranylgeranylation inhibitors may provide selective inhibition of key pathogenic cytokines that drive the autoimmune response in MS; their use represents a promising therapeutic approach that requires further clinical testing.
Visible‐Light‐Triggered Direct Benzoyloxylation of Electron‐Rich Arenes at Room Temperature without Chelation Assistance
Authors: Rao Honghua , Wang Ping , Li Chao‐Jun
Published: October 2012

A RuII photocatalytic method was developed for the direct mono‐benzoyloxylation of electron‐rich aromatic and heteroaromatic systems even with an excess amount of benzoyl peroxide. The reaction was conducted at room temperature under visible light. The direct ArC–H benzoyloxylations occur without the assistance of any directing groups and can also tolerate various functional groups that have already shown diverse reactivities in transition‐metal catalysis.
Investigation of Ni Foam Effect for Direct Borohydride Fuel Cell
Authors: Celik C. , Boyaci San F. G. , Sarac H. I.
Published: October 2012

Ni foam has been used as a substrate for the anode electrocatalyst in our previous works. In this study, the effect of nickel foam as an anode electrode in direct borohydride cells has been investigated under steady state/steady‐flow and uniform state/uniform‐flow systems, since nickel has catalytic property. Cathode catalyst used has been 0.3 mg cm–2 on PTFE‐treated Toray carbon paper. The results have showed that power densities have increased by increasing the temperature. Peak power densities of 5.01 and 9.55 mW cm–2 have been achieved at 25 and 60 °C, respectively, for 1.5 mol dm–3 NaBH4. On the other hand, the electrochemical performance has not been significantly different by the sodium borohydride concentration; only a small increase of power density has been observed in steady state/steady‐flow system, and only a small decrease of fuel utilization ratio has been obtained in uniform state/uniform‐flow systems.
MicroRNAs: New Tools for Diagnosis, Prognosis, and Therapy in Hepatocellular Carcinoma?
Authors: Giordano Silvia , Columbano Amedeo
Published: October 2012

MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs involved in the regulation of gene expression and protein translation. Many studies have shown that they play a crucial role in driving organ and tissue differentiation during embryogenesis and in the fine-tuning of fundamental biological processes, such as proliferation and apoptosis. Growing evidence indicates that their deregulation plays an important role in cancer onset and progression as well, where they act as oncogenes or oncosuppressors. In this review, we highlight the most recent findings regarding the role of miRNAs in hepatocellular carcinoma (HCC) by analyzing the possible mechanisms by which they contribute to this neoplasm. Moreover, we discuss the possible role of circulating miRNAs as biomarkers, a field that needs urgent improvement in the clinical surveillance of HCC, and the fascinating possibility of using them as therapeutic targets or drugs themselves.
Circulating neutrophil dysfunction in acute liver failure
Authors: Taylor Nicholas J. , Nishtala Anirudh , Manakkat Vijay Godhev K. , Abeles Daniel R. , Auzinger Georg , Bernal William , Ma Yun , Wendon Julia A. , Shawcross Debbie L.
Published: October 2012

Systemic inflammation and susceptibility to developing sepsis is common in acute liver failure (ALF) resulting in tissue damage and organ failure. This study characterized the function of circulating neutrophils in 25 patients with ALF and subacute liver failure (SALF). ALF (n = 15) / SALF (n = 10) patients were prospectively studied and compared with 11 healthy (HC) and 6 septic controls (SC). Neutrophils were isolated on admission to intensive care and every 3–4 days until death / liver transplantation / recovery. Neutrophil phenotype was determined using fluorochrome-labeled antibodies to CD16 and CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA) was determined using fluorescein isothiocyanate-labeled opsonized

Escherichia coli

and oxidative burst (OB) was determined by the percentage of neutrophils producing reactive oxygen species (ROS) at rest and after stimulation with opsonized

E. coli
. Physiological variables, biochemistry, arterial ammonia, microbiology, and outcomes were collected. Plasma pro- and antiinflammatory cytokine profiles were performed by enzyme-linked immunosorbent assay. Neutrophil expression of CD16 which recognizes the FcγRIII region of immunoglobulin G was significantly reduced in the ALF cohort (

P

< 0.001) on day 1 compared to HC. NPA was significantly impaired in the SALF cohort compared to HC (

P

< 0.01). Impaired NPA in the ALF and SALF cohorts on admission predicted nonsurvival without liver transplantation (

P

= 0.01). Spontaneous neutrophil production of ROS was not significantly increased in any of the cohorts.

E. coli
-stimulated OB was preserved in ALF/SALF cohorts but was significantly impaired in the SC group (

P

< 0.05).

Conclusion
: Circulating neutrophils in ALF/SALF have impaired bacteriocidal function similar to that seen in severe sepsis. Neutrophil function indices are important biomarkers in ALF and may be implicated in the development of organ dysfunction and the increased susceptibility to developing sepsis. (Hepatology 2013)
Causes of death in patients with hepatitis B: A natural history cohort study in the United States
Authors: Szpakowski Jean-Luc , Tucker Lue-Yen
Published: October 2012

The natural history of hepatitis B virus (HBV) infection in a U.S. population has not been well described. We identified the causes of death in 6,689 health plan members infected with HBV who were followed between March 1, 1996 and December 31, 2005. Causes of death were grouped into HBV-related (subdivided into decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]), cancer, cardiovascular, and other/unknown. The study cohort included 3,244 females and 3,445 males; 68.3% were of Asian-Pacific Islander (API) descent, 11.8% were white (non-Hispanic), and 19.9% were of other or unknown race. Exposure to HBV antivirals and preexisting comorbidities were uncommon. Males had higher overall 10-year death rates than females, both for total deaths (8.9% versus 4.1%) and for HBV-related deaths (4.8% versus 1.2%). The death rate rose markedly with increasing age, and approximately 40% of all deaths in subjects over the age of 40 were HBV related. The death rate from HCC was twice that of DCC. HCC deaths represented 70% of cancer deaths in males and 37% in females. On multivariable analysis, when subjects with antecedent HCC and DCC were excluded, the only significant predictor of HBV mortality in both sexes was age. Conclusion: HBV was the cause of death in over 40% of those who died during the study, and the mortality increased markedly with increasing age over 40 in males and over 50 in females. HBV-related mortality was four times more common in males than in females and was as common in non-Asians as in those of API origin. HBV-related deaths were twice as common from HCC as from DCC. (HEPATOLOGY 2013)
Metal‐Free 2,2,6,6‐Tetramethylpiperidin‐1‐yloxy Radical (TEMPO) Catalyzed Aerobic Oxidation of Hydroxylamines and Alkoxyamines to Oximes and Oxime Ethers
Authors: Wertz Sebastian , Studer Armido
Published: October 2012

TEMPO‐Mediated oxidation of hydroxylamines (=hydroxyamines) and alkoxyamines to the corresponding oxime derivatives is reported (TEMPO=2,2,6,6‐tetramethylpiperidin‐1‐yloxy radical; Scheme 2). These environmentally benign oxidations proceed in good to excellent yields (Table 1). For alkoxyamines, oxidation to the corresponding oxime ethers can be performed by using dioxygen as a terminal oxidant in the presence of 5–10 mol‐% of TEMPO or 4‐substituted derivatives thereof as a catalyst (Scheme 3 and Table 2). Importantly, benzyl bromides can directly be transformed to oxime ethers via in situ alkoxyamine formation by a nucleophilic substitution followed by TEMPO‐mediated oxidation (Scheme 4 and Table 3).
Enantioselective Synthesis of (−)‐(R)‐Cordiachromene and (−)‐(R)‐Dictyochromenol Utilizing Intramolecular SNAr Reaction
Authors: Noda Yoshihiro , Yasuda Misato
Published: October 2012

A simple and efficient enantioselective synthesis of chromene, (−)‐(R)‐cordiachromene (1), and (−)‐(R)‐dictyochromenol (2) has been accomplished. This convergent synthesis utilizes intramolecular SNAr reaction for the formation of chroman ring, and Seebach's method of ‘self‐reproduction of chirality’ should establish the (R)‐configuration of the C(2) side chain as key steps.
Asymmetric Syntheses of the Sex Pheromones of Pine Sawflies, Their Homologs and Stereoisomers
Authors: Zheng Jian‐Feng , Lan Hong‐Qiao , Yang Rui‐Feng , Peng Qi‐Long , Xiao Zhen‐Hua , Tuo Shi‐Chuan , Hu Kong‐Zhen , Xiang Yong‐Gang , Wei Zhen , Zhang Zhen , Huang Pei‐Qiang
Published: October 2012

We describe efficient and flexible enantioselective syntheses of the active enantiomers of the pheromones of pine sawflies, including the species Diprion jingyuanensis, their homologs and, stereoisomers, as well as those identified from the Chinese species Diprion jingyuanensis, i.e., 126. A total of 48 compounds, including acetates 78–101 and propanoates 102–125, have been synthesized. Our general approach towards these compounds originated from the commercially available chirons diethyl (S)‐ and (R)‐malates, as well as ethyl (R)‐3‐hydroxybutanoate. The Seebach asymmetric methylation was employed in a key step to control additional configuration.
Helical Structures of Bicyclic α‐Amino Acid Homochiral Oligomers with the Stereogenic Centers at the Side‐Chain Fused‐Ring Junctions
Authors: Anan Kosuke , Demizu Yosuke , Oba Makoto , Kurihara Masaaki , Doi Mitsunobu , Suemune Hiroshi , Tanaka Masakazu
Published: October 2012

Chiral bicyclic α‐amino acid (R,R)‐Ab5,6=c with stereogenic centers at the γ‐position of fused‐ring junctions, and its enantiomer (S,S)‐Ab5,6=c, were synthesized. The CD spectra of (R,R)‐Ab5,6=c oligomers indicated that the (R,R)‐Ab5,6=c hexapeptide formed a mixture of right‐handed (P)‐ and left‐handed (M)‐310‐helices, while, in the (R,R)‐Ab5,6=c nonapeptide, a right‐handed (P)‐310‐helix slightly dominated over the (M)‐helix. X‐Ray crystallographic analyses of (S,S)‐tripeptide and (R,R)‐hexapeptide revealed that both the tripeptide and hexapeptide formed a mixture of (P)‐ and (M)‐310‐helices, respectively. These results indicated that the side‐chain environments around the stereogenic centers are particularly important to control the helical‐screw handedness of foldamers.
The MoritaBaylisHillman Reaction of Chiral Highly Oxygenated Cyclopent‐2‐enones
Authors: Masusai Chonticha , Soorukram Darunee , Kuhakarn Chutima , Tuchinda Patoomratana , Pakawatchai Chaveng , Reutrakul Vichai , Pohmakotr Manat
Published: October 2012

The MoritaBaylisHillman (MBH) reactions of (4S,5R,7R,8R)‐ and (4R,5R,7R,8R)‐4‐hydroxy‐7,8‐dimethoxy‐7,8‐dimethyl‐6,9‐dioxaspiro[4.5]dec‐2‐en‐1‐ones (2 and 3, resp.) with aldehydes using various catalysts were studied. A combination of Bu3P/phenol in THF was found being optimum conditions giving the corresponding MBH adducts with high diastereoisomeric ratios. After separation, each stereomerically pure isomer of the MBH adducts was subjected to hydrolysis employing 1% aq. CF3COOH (TFA) in a water bath of an ultrasonic cleaner to afford the corresponding polyhydroxylated cyclopentenones in good yields.
New Aspects of 1,3‐Diphosphacyclobutane‐2,4‐diyls
Authors: Yoshifuji Masaaki , Hirano Yuichi , Schnakenburg Gregor , Streubel Rainer , Niecke Edgar , Ito Shigekazu
Published: October 2012

1,3‐Di(tert‐butyl)‐2,4‐bis[2,4,6‐tri(tert‐butyl)phenyl]‐1,3‐diphosphacyclobutane‐2,4‐diyl was formed from [2,4,6‐tri(tert‐butyl)phenyl]phosphaacetylene and t‐BuLi. In addition, the X‐ray diffraction analysis was carried out, together with theoretical calculations of the structure and NMR data.
Nucleophilic Fluoroalkylation of α,β‐Unsaturated Carbonyl Compounds with α‐Fluorinated Sulfones: Investigation of the Reversibility of 1,2‐Additions and the Formation of 1,4‐Adducts
Authors: Shen Xiao , Ni Chuanfa , Hu Jinbo
Published: October 2012

A detailed investigation of the reactions of PhSO2CF2H and PhSO2CH2F with (E)‐chalcone (=(E)‐1,3‐diphenylprop‐2‐en‐1‐one) at low temperatures revealed that these two reactions were kinetically controlled, and the ratios of 1,2‐ vs. 1,4‐adducts, which did not change much over time at these temperatures, reflect the relative rates of the two reaction pathways. The controlled experiments of converting the PhSO2CF2‐ and PhSO2CHF‐substituted 1,2‐adducts to 1,4‐adducts showed that these isomerizations are not favored due to the low stability and hard‐soft nature of PhSO2CF$\rm{{_{2}^{-}}}$ and PhSO2CHF− anions. Moreover, taking advantage of the remarkable stability and softness of (PhSO2)2CF− anion, an efficient thermodynamically controlled isomerization of (PhSO2)2CF‐substituted 1,2‐adduct to 1,4‐adduct was achieved for the first time.
Asymmetric Synthesis of β2‐homo‐tert‐Leucine via Radical Addition to Enantiopure N‐Fumaroylhexahydrobenzooxazolidin‐2‐one
Authors: Escudero‐Casao Margarita , Juaristi Eusebio
Published: October 2012

β‐Amino acids are key structural elements in unnatural peptides, peptidomimetics, and many other physiologically active compounds. In view of their importance, we have developed an efficient synthetic route that provides highly enantiomerically enriched (R)‐ and (S)‐H‐β2‐htLeu‐OH via highly diastereo‐ and regioselective addition of tert‐butyl radical to enantiomerically pure N‐fumaroyloxazolidinones, followed by removal of the chiral auxiliary, Curtius rearrangement, ester hydrolysis, and catalytic hydrogenolysis.