bluuebunny/crossref_metadata_2025 huggingface dataset:
Anaerobic Digestion of Solid Wastes Needs Research to Face an Increasing Industrial Success
Authors: Buffiere Pierre , Delgadillo Mirquez Liliana , Steyer Jean Philippe , Bernet Nicolas , Delgenes Jean Philippe
Published: October 2008

Anaerobic digestion of solid wastes is an emerging solution for both waste management and energy production. The high complexity of the process is mostly attributed to the absence of descriptors for the design and the prediction of such a process. This paper presents an approach for the description of organic matter based on several biochemical parameters, established on 22 different organic wastes. The lignocellulosic content is the most important parameter for the prediction of anaerobic biodegradability and methane production; in addition, the knowledge of the carbohydrate, lipid and protein contents is also crucial and makes possible a prediction of the intrinsic kinetics of the reaction.
Aerobic Composting of Poultry Manure and Wheat Straw-Kinetic and Reactor Model
Authors: Petric Ivan
Published: October 2008

Laboratory-scale aerobic composting tests with mixture of poultry manure and wheat straw were conducted in closed thermally insulated column reactors with effective volumes of 1 L and 32 L. Two 14-day experiments with two different mixture ratios (manure to straw, 2.77:1 and 5.25:1 on dry weight, respectively) were performed in order to compare the performances of composting process in both reactors as well to obtain the parameter values in the kinetic model and to validate proposed kinetic and reactor model in this work. The maximum temperature of 64.6°C was reached after 2.1 days in the large reactor and 64.5°C after 1.3 days in the small reactor. The temperature in these reactors was maintained above 55°C for 2 days, which should be sufficient to maximize sanitation and to destroy pathogens. The greatest mass of carbon dioxide was generated during the first 3 days. The maximum consumption of oxygen was noticed in the exit gas mixtures from both reactors after the first day of the process (the small reactor 16.0 vol. %, the large reactor 11.7 vol. %). The maximum emission of ammonia was observed from the small reactor after first day and from large reactor after the third day. The organic matter content of the materials decreased in both reactors during the process, but this reduction was greater in the large reactor (47.60%) than in the small reactor (41.36%). The proposed kinetic and reactor model was described by a differential equation set with 12 dynamic state variables: mass of organic matter, mass of oxygen, mass of dissolved carbon dioxide, mass of dissolved ammonia, mass of water in the substrate, molar amount of O2 (gas phase), molar amount of CO2 (gas phase), molar amount of NH3 (gas phase), molar amount of H2O vapour (gas phase), molar amount of N2 (gas phase), temperature of gas phase, temperature of solid-liquid phase. In the proposed kinetic model, four kinetic parameters were calculated. The model was validated by the results of several experimentally measured dynamic state variables (temperature of substrate, conversion of organic matter conversion, concentration of carbon dioxide, concentration of oxygen). Comparisons of experimental and simulation results showed good agreement during the whole duration of the process in a reactor, except for ammonia (good agreement was achieved for the first four days and for the last three days of the process). Different simulation scenarios were performed with the model in order to study the effects of initial moisture content, airflow rates and air temperature on the substrate temperature and organic matter conversion. A sensitivity analysis showed that two of four kinetic parameters had a great influence on all three objective functions (maximum conversion of organic matter, maximum concentration of carbon dioxide and maximum substrate temperature).
Comment on 'Technological Revolutions and the Evolution of Industrial Structures' (by Giovanni Dosi, Alfonso Gambardella, Marco Grazzi, and Luigi Orsenigo)
Authors: Langlois Richard N
Published: October 2008

The recent article in Capitalism and Society by Dosi et al., as well as the accompanying discussion by William Lazonick, misunderstand and mischaracterize the argument of my 2003 paper "The Vanishing Hand." More importantly, some of the central claims these articles make about the organization of the so-called New Economy do not withstand careful scrutiny.
Household Debt in the Consumer Age: Source of Growth--Risk of Collapse
Authors: Cynamon Barry Z. , Fazzari Steven M.
Published: October 2008

The 2008 U.S. financial upheaval raises important questions about the sources of household consumption and debt growth, along with their macroeconomic effects. We argue that spending and financial preferences evolve as social norms interact with both cultural trends and institutional changes in household finance. We identify historical forces that raised consumption and debt over the past quarter century and interpret these events with Hyman Minsky's financial cycle framework. Strong consumption helped moderate recessions and boost growth since the mid 1980s. But unprecedented household debt has now culminated in a financial crisis that threatens to cause a deep recession.
Economic Forecasting in a Changing World
Authors: Clements Michael P. , Hendry David F.
Published: October 2008

This article explains the basis for a theory of economic forecasting developed over the past decade by the authors. The research has resulted in numerous articles in academic journals, two monographs, Forecasting Economic Time Series, 1998, Cambridge University Press, and Forecasting Nonstationary Economic Time Series, 1999, MIT Press, and three edited volumes, Understanding Economic Forecasts, 2001, MIT Press, A Companion to Economic Forecasting, 2002, Blackwells, and the Oxford Bulletin of Economics and Statistics, 2005. The aim here is to provide an accessible, non-technical, account of the main ideas. The interested reader is referred to the monographs for derivations, simulation evidence, and further empirical illustrations, which in turn reference the original articles and related material, and provide bibliographic perspective.
The Historical Origins of 'Open Science': An Essay on Patronage, Reputation and Common Agency Contracting in the Scientific Revolution
Authors: David Paul A.
Published: October 2008

This essay examines the economics of patronage in the production of knowledge and its influence upon the historical formation of key elements in the ethos and organizational structure of publicly funded `open science.' The emergence during the late sixteenth and early seventeenth centuries of the idea and practice of `open science' was a distinctive and vital organizational aspect of the Scientific Revolution. It represented a break from the previously dominant ethos of secrecy in the pursuit of Nature's Secrets, to a new set of norms, incentives, and organizational structures that reinforced scientific researchers' commitments to rapid disclosure of new knowledge. The rise of `cooperative rivalries' in the revelation of new knowledge, is seen as a functional response to heightened asymmetric information problems posed for the Renaissance system of court-patronage of the arts and sciences; pre-existing informational asymmetries had been exacerbated by the claims of mathematicians and the increasing practical reliance upon new mathematical techniques in a variety of `contexts of application.' Reputational competition among Europe's noble patrons motivated much of their efforts to attract to their courts the most prestigious natural philosophers, was no less crucial in the workings of that system than was the concern among their would-be clients to raise their peer-based reputational status. In late Renaissance Europe, the feudal legacy of fragmented political authority had resulted in relations between noble patrons and their savant-clients that resembled the situation modern economists describe as `common agency contracting in substitutes' -- competition among incompletely informed principals for the dedicated services of multiple agents. These conditions tended to result in contract terms (especially with regard to autonomy and financial support) that left agent client members of the nascent scientific communities better positioned to retain larger information rents on their specialized knowledge. This encouraged entry into their emerging disciplines, and enabled them collectively to develop a stronger degree of professional autonomy for their programs of inquiry within the increasingly specialized and formal scientific academies (such the Académie royale des Sciences and the Royal Society) that had attracted the patronage of rival absolutist States of Western Europe during the latter part of the seventeenth century. The institutionalization of `open science' that took place within those settings is shown to have continuities with the use by scientists of the earlier humanist academies, and with the logic of regal patronage, rather than being driven by the material requirements of new observational and experimental techniques.
Comment on "Economic Forecasting in a Changing World" (by Michael Clements and David Hendry)
Authors: Ericsson Neil R.
Published: October 2008

Michael Clements and David Hendry make realistic assumptions about the nature of the economy and the models used to forecast it. Under those assumptions, Clements and Hendry clarify why forecasting models work when they do, and why they don't work when they don't. Their research also suggests how to improve the forecasting abilities of existing models.A taxonomy of the sources of forecast error underpins Clements and Hendry's analysis. In my comments, I summarize their taxonomy; illustrate several implications, including for predictable and unpredictable forecast uncertainty; and re-examine forecast criteria, focusing on how mean square forecast errors can mislead.
Development of Rigorous and Reduced Heterogeneous Dynamic Models for Fixed Bed Catalytic Reactor and Three-Phase Catalytic Slurry Reactor
Authors: Vasco de Toledo Eduardo Coselli , Mariano Adriano Pinto , de Morais Edvaldo Rodrigo , Stremel Dile Pontarolo , Meyer João Frederico da Costa Azevedo , Maciel Filho Rubens
Published: October 2008

In this work, the dynamic behavior of two chemical reactors (Fixed Bed Catalytic Reactor and the Three-Phase Reactor), in which different reactions of great industrial interest take place, is presented. Rigorous and reduced models were developed and their capabilities to adequately predict the dynamic behavior of these reactors were compared, indicating which model is more suitable for a specific application (design, optimization and control). Different approaches [Classic, Hermite, Finlayson, Pirkle, Dixion, Generic and Orthogonal collocation (one point)] were used to obtain the reduced models. With these techniques, a mathematical order reduction was carried out, which eliminates the spatial co-ordinate (of the catalyst particle or of the reactor) and promotes radially lumped-differential formulations. The proposed rigorous models were able to predict the main characteristics of the dynamic behavior of the fixed bed catalytic reactor as well as of the three-phase reactor, including the inverse response phenomena and the hot spot present in the former. This knowledge is essential to design and control these reactors. The computational time demanded for the solution of the rigorous models is high in comparison to the reduced ones, which restricts the use of the rigorous models to cases where time is not a limiting factor. Otherwise, when on-line applications are required, the reduced models are more adequate. The models based on reduction techniques overcame computational burden with a faster and easier numerical solution, as well as other difficulties found in rigorous heterogeneous models, especially related to the large number of parameters and sophisticated numerical procedures required by the solution.
Prediction of Double Retrograde Vaporization by Hybrid Global-Local Optimization Using Fuzzy Clustering Means
Authors: Henderson Nelio , Sacco Wagner Figueiredo
Published: October 2008

Retrograde vaporization calculation is a hard problem, which possesses several solutions and demands a robust algorithm. In the present work, we solved the double retrograde vaporization problem by hybrid global-local optimization. In fact, we propose a new methodology that involves fuzzy clustering means together with Luus-Jaakola and Nelder-Mead algorithms. We applied the proposed methodology to solve the double retrograde vaporization problem for binary systems of methane + n-butane. For this mixture, the dew point curve exhibits an S-shape at temperatures slightly below the critical temperature of the more volatile component. This binary mixture was modeled using the original Peng-Robinson equation of state and the classical one-fluid van der Waals mixing rule.
On the Interaction between Incisor Crown-Root Morphology and Third-Order Angulation
Authors: Knösel Michael , Jung Klaus , Attin Thomas , Engelke Wilfried , Kubein-Meesenburg Dietmar , Gripp-Rudolph Liliam , Attin Rengin
Published: October 2008

Objective: To evaluate the significance of crown-root angles (CRAs) by testing the null hypothesis that there are no significant differences in deviations of third-order angles to axial inclination values between Angle Class II division 2 incisors and a neutral occlusion control sample.

Materials and Methods: The study group comprised ntotal = 130 whites with either Angle Class II division 2 (n1 = 62; group A) or neutral (n2 = 68; control group B) occlusal relationships. Upper central incisor inclination (U1) was assessed with reference to the cephalometric lines NA and palatal plane (U1NA/deg, U1PP/deg). Craniofacial sagittal and vertical relations were classified using angles SNA, SNB, ANB, and NSL-PP. Third-order angles were derived from corresponding dental cast pairs using an incisor inclination gauge. Welch's two-sample t-tests (α-level: .05) were used to test the null hypothesis. Single linear regression was applied to determine third-order angle values as a function of axial inclination values (U1NA, U1PP) or sagittal craniofacial structures (ANB angle), separately for group A and B.

Results: The discrepancy between axial inclination (U1NA, U1PP) and third-order angles is significantly different (P < .001) between groups A and B. Regression analysis revealed a simply moderate correlation between third-order measurements and axial inclinations or sagittal craniofacial structures.

Conclusion: The hypothesis is rejected. The results of this study warn against the use of identical third-order angles irrespective of diminished CRAs typical for Angle Class II division 2 subjects. Routine CRA assessment may be considered in orthodontic treatment planning of Angle Class II division 2 cases.
Skeletal Muscle–Specific Deletion of Lipoprotein Lipase Enhances Insulin Signaling in Skeletal Muscle but Causes Insulin Resistance in Liver and Other Tissues
Authors: Wang Hong , Knaub Leslie A. , Jensen Dalan R. , Young Jung Dae , Hong Eun-Gyoung , Ko Hwi-Jin , Coates Alison M. , Goldberg Ira J. , de la Houssaye Becky A. , Janssen Rachel C. , McCurdy Carrie E. , Rahman Shaikh M. , Soo Choi Cheol , Shulman Gerald I. , Kim Jason K. , Friedman Jacob E. , Eckel Robert H.
Published: October 2008

OBJECTIVE

Skeletal muscle–specific LPL knockout mouse (SMLPL−/−) were created to study the systemic impact of reduced lipoprotein lipid delivery in skeletal muscle on insulin sensitivity, body weight, and composition.

RESEARCH DESIGN AND METHODS

Tissue-specific insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp and 2-deoxyglucose uptake. Gene expression and insulin-signaling molecules were compared in skeletal muscle and liver of SMLPL−/− and control mice.

RESULTS

Nine-week-old SMLPL−/− mice showed no differences in body weight, fat mass, or whole-body insulin sensitivity, but older SMLPL−/− mice had greater weight gain and whole-body insulin resistance. High-fat diet feeding accelerated the development of obesity. In young SMLPL−/− mice, insulin-stimulated glucose uptake was increased 58% in the skeletal muscle, but was reduced in white adipose tissue (WAT) and heart. Insulin action was also diminished in liver: 40% suppression of hepatic glucose production in SMLPL−/− vs. 90% in control mice. Skeletal muscle triglyceride was 38% lower, and insulin-stimulated phosphorylated Akt (Ser473) was twofold greater in SMLPL−/− mice without changes in IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase activity. Hepatic triglyceride and liver X receptor, carbohydrate response element–binding protein, and PEPCK mRNAs were unaffected in SMLPL−/− mice, but peroxisome proliferator–activated receptor (PPAR)-γ coactivator-1α and interleukin-1β mRNAs were higher, and stearoyl–coenzyme A desaturase-1 and PPARγ mRNAs were reduced.

CONCLUSIONS

LPL deletion in skeletal muscle reduces lipid storage and increases insulin signaling in skeletal muscle without changes in body composition. Moreover, lack of LPL in skeletal muscle results in insulin resistance in other key metabolic tissues and ultimately leads to obesity and systemic insulin resistance.
Elevated Expression of Osteopontin May Be Related to Adipose Tissue Macrophage Accumulation and Liver Steatosis in Morbid Obesity
Authors: Bertola Adeline , Deveaux Vanessa , Bonnafous Stéphanie , Rousseau Déborah , Anty Rodolphe , Wakkach Abdelilah , Dahman Moncef , Tordjman Joan , Clément Karine , McQuaid Siobhán E. , Frayn Keith N. , Huet Pierre-Michel , Gugenheim Jean , Lotersztajn Sophie , Le Marchand-Brustel Yannick , Tran Albert , Gual Philippe
Published: October 2008

OBJECTIVE—Osteopontin (OPN) plays an important role in the development of insulin resistance and liver complications in dietary murine models. We aimed to determine the expression pattern of OPN and its receptor CD44 in obese patients and mice according to insulin resistance and liver steatosis.

RESEARCH DESIGN AND METHODS—OPN and CD44 expressions were studied in 52 morbidly obese patients and in mice. Cellular studies were performed in HepG2 cells.

RESULTS—Hepatic OPN and CD44 expressions were strongly correlated with liver steatosis and insulin resistance in obese patients and mice. This increased OPN expression could be due to the accumulation of triglycerides, since fat loading in HepG2 promotes OPN expression. In contrast, OPN expression in adipose tissue (AT) was enhanced independently of insulin resistance and hepatic steatosis in obese patients. The elevated OPN expression in AT was paralleled with the AT macrophage infiltration, and both phenomena were reversed after weight loss. The circulating OPN level was slightly elevated in obese patients and was not related to liver steatosis. Further, AT did not appear to secrete OPN. In contrast, bariatric surgery–induced weight loss induced a strong increase in circulating OPN.

CONCLUSIONS—The modestly elevated circulating OPN levels in morbidly obese patients were not related to liver steatosis and did not appear to result from adipose tissue secretion. In subcutaneous AT, expression of OPN was directly related to macrophage accumulation independently from liver complications. In contrast, hepatic OPN and CD44 expressions were related to insulin resistance and steatosis, suggesting their local implication in the progression of liver injury.
Mid- and Late-Life Diabetes in Relation to the Risk of Dementia
Authors: Xu Weili , Qiu Chengxuan , Gatz Margaret , Pedersen Nancy L. , Johansson Boo , Fratiglioni Laura
Published: October 2008

OBJECTIVE—We aimed to verify the association between diabetes and the risk of dementia, Alzheimer's disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association.

RESEARCH DESIGN AND METHODS—This study included 13,693 twin individuals aged ≥65 years. Dementia was diagnosed according to DSM-IV (Diagnostic Manual of Mental Disorders, 4th ed.) criteria. Information on diabetes was collected from the inpatient registry and self- or informant-reported history of diabetes. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models and 2) cotwin matched case-control analysis for dementia-discordant twin pairs using conditional logistic regression.

RESULTS—Of all participants, 467 were diagnosed with dementia, including 292 with Alzheimer's disease and 105 with vascular dementia, and an additional 170 were diagnosed with questionable dementia. Diabetes was present in 1,396 subjects. In GEE models, diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51–2.38) for dementia, 1.69 (1.16–2.36) for Alzheimer's disease, and 2.17 (1.36–3.47) for vascular dementia. Compared with late-life diabetes (onset age ≥65 years), the risk effect of mid-life diabetes (onset age <65 years) on dementia was stronger. Conditional logistic analysis of 210 dementia-discordant twin pairs led to ORs of 2.41 (1.05–5.51) and 0.68 (0.30–1.53) for dementia related to mid- and late-life diabetes, respectively.

CONCLUSIONS—Diabetes increases the risk of Alzheimer disease and vascular dementia. The risk is stronger when diabetes occurs at mid-life than in late life. Genetic and early-life environmental factors might contribute to the late-life diabetes–dementia association but could not account for the mid-life diabetes–dementia association.
Hepatic Stearoyl-CoA Desaturase (SCD)-1 Activity and Diacylglycerol but Not Ceramide Concentrations Are Increased in the Nonalcoholic Human Fatty Liver
Authors: Kotronen Anna , Seppänen-Laakso Tuulikki , Westerbacka Jukka , Kiviluoto Tuula , Arola Johanna , Ruskeepää Anna-Liisa , Orešič Matej , Yki-Järvinen Hannele
Published: October 2008

OBJECTIVE—To determine whether 1) hepatic ceramide and diacylglycerol concentrations, 2) SCD1 activity, and 3) hepatic lipogenic index are increased in the human nonalcoholic fatty liver.

RESEARCH DESIGN AND METHODS—We studied 16 subjects with (n = 8) and without (n = 8) histologically determined nonalcoholic fatty liver (NAFL+ and NAFL−) matched for age, sex, and BMI. Hepatic concentrations of lipids and fatty acids were quantitated using ultra-performance liquid chromatography coupled to mass spectrometry and gas chromatography.

RESULTS—The absolute (nmol/mg) hepatic concentrations of diacylglycerols but not ceramides were increased in the NAFL+ group compared with the NAFL− group. The livers of the NAFL+ group contained proportionally less long-chain polyunsaturated fatty acids as compared with the NAFL− group. Liver fat percent was positively related to hepatic stearoyl-CoA desaturase 1 (SCD1) activity index (r = 0.70, P = 0.003) and the hepatic lipogenic index (r = 0.54, P = 0.030). Hepatic SCD1 activity index was positively related to the concentrations of diacylglycerols (r = 0.71, P = 0.002) but not ceramides (r = 0.07, NS).

CONCLUSIONS—We conclude that diacylglycerols but not ceramides are increased in NAFL. The human fatty liver is also characterized by depletion of long polyunsaturated fatty acids in the liver and increases in hepatic SCD1 and lipogenic activities.
Restoration of Hepatic Glucokinase Expression Corrects Hepatic Glucose Flux and Normalizes Plasma Glucose in Zucker Diabetic Fatty Rats
Authors: Torres Tracy P. , Catlin ReEtta L. , Chan Robert , Fujimoto Yuka , Sasaki Noriyasu , Printz Richard L. , Newgard Christopher B. , Shiota Masakazu
Published: October 2008

OBJECTIVE—We examined in 20-week-old Zucker diabetic fatty (ZDF) rats whether restoration of hepatic glucokinase (GK) expression would alter hepatic glucose flux and improve hyperglycemia.

RESEARCH DESIGN AND METHODS—ZDF rats were treated at various doses with an adenovirus that directs the expression of rat liver GK (AdvCMV-GKL) dose dependently, and various metabolic parameters were compared with those of nondiabetic lean littermates (ZCL rats) before and during a hyperglycemic clamp. Viral infection per se did not affect hepatic GK activity, since expression of a catalytically inactive form of GK did not alter endogenous hepatic GK activity.

RESULTS—ZDF rats compared with ZCL rats have lower hepatic GK activity (11.6 ± 1.9 vs. 32.5 ± 3.2 mU/mg protein), marked hyperglycemia (23.9 ± 1.2 vs. 7.4 ± 0.3 mmol/l), higher endogenous glucose production (80 ± 3 vs. 38 ± 3 μmol · kg−1 · min−1), increased glucose-6-phosphatase flux (150 ± 11 vs. 58 ± 8 μmol · kg−1 · min−1), and during a hyperglycemic clamp, a failure to suppress endogenous glucose production (80 ± 7 vs. −7 ± 4 μmol · kg−1 · min−1) and promote glucose incorporation into glycogen (15 ± 5 vs. 43 ± 3 μmol/g liver). Treatment of ZDF rats with different doses of AdvCMV-GKL, which restored hepatic GK activity to one to two times that of ZCL rats, normalized plasma glucose levels and endogenous glucose production. During a hyperglycemic clamp, glucose production was suppressed and glucose incorporation into glycogen was normal.

CONCLUSIONS—Alteration of hepatic GK activity in ZDF rats has profound effects on plasma glucose and hepatic glucose flux.
Molecules after 10 Years: the Best is Yet to Come
Authors: McPhee Derek , Lin Shu-Kun
Published: October 2008

The year 2005 that has just started marks a very special anniversary for Molecules, its publishers, and Editorial Board, for with this issue we start publication of our 10th volume.[...]
Macromolecules Applied to Pharmaceutical Chemistry
Authors: Salomon Claudio
Published: October 2008

Macromolecular and polymer science have evolved significantly over the past few years, with remarkable advances in many areas such as polymeric drugs, self-assembly systems, implant materials, drug delivery systems and controlled drug release.[...]
Scleroglucan: A Versatile Polysaccharide for Modified Drug Delivery
Authors: Coviello Tommasina , Palleschi Antonio , Grassi Mario , Matricardi Pietro , Bocchinfuso Gianfranco , Alhaique Franco
Published: October 2008

Scleroglucan is a natural polysaccharide, produced by fungi of the genus Sclerotium, that has been extensively studied for various commercial applications (secondary oil recovery, ceramic glazes, food, paints, etc.) and also shows several interesting pharmacological properties. This review focuses its attention on the use of scleroglucan, and some derivatives, in the field of pharmaceutics and in particular for the formulation of modified-release dosage forms. The reported investigations refer mainly to the following topics: natural scleroglucan suitable for the preparation of sustained release tablets and ocular formulations; oxidized and crosslinked scleroglucan used as a matrix for dosage forms sensitive to environmental conditions; co-crosslinked scleroglucan/gellan whose delivery rate can be affected by calcium ions. Furthermore, a novel hydrogel obtained with this polysaccharide and borate ions is described, and the particular structure of this hydrogel network has been interpreted in terms of conformational analysis and molecular dynamics. Profound attention is devoted to the mechanisms involved in drug release from the tested dosage forms that depend, according to the specific preparation, on swelling and/or diffusion. Experimental data are also discussed on the basis of a mathematical approach that allows a better understanding of the behavior of the tested polymeric materials.
Polymers for DNA Delivery
Authors: Eliyahu H. , Barenholz Y. , Domb A. J.
Published: October 2008

Nucleic acid delivery has many applications in basic science, biotechnology, agriculture, and medicine. One of the main applications is DNA or RNA delivery for gene therapy purposes. Gene therapy, an approach for treatment or prevention of diseases associated with defective gene expression, involves the insertion of a therapeutic gene into cells, followed by expression and production of the required proteins. This approach enables replacement of damaged genes or expression inhibition of undesired genes. Following two decades of research, there are two major methods for delivery of genes. The first method, considered the dominant approach, utilizes viral vectors and is generally an efficient tool of transfection. Attempts, however, to resolve drawbacks related with viral vectors (e.g., high risk of mutagenicity, immunogenicity, low production yield, limited gene size, etc.), led to the development of an alternative method, which makes use of non-viral vectors. This review describes non-viral gene delivery vectors, termed "self-assembled" systems, and are based on cationic molecules, which form spontaneous complexes with negatively charged nucleic acids. It introduces the most important cationic polymers used for gene delivery. A transition from in vitro to in vivo gene delivery is also presented, with an emphasis on the obstacles to achieve successful transfection in vivo.
Polymeric Particulates to Improve Oral Bioavailability of Peptide Drugs
Authors: Delie Florence , Blanco-Príeto María José
Published: October 2008

Oral administration remains the most convenient way of delivering drugs. Recent advances in biotechnology have produced highly potent new molecules such as peptides, proteins and nucleic acids. Due to their sensitivity to chemical and enzymatic hydrolysis as well as a poor cellular uptake, their oral bioavailability remains very low. Despite sophisticated new delivery systems, the development of a satisfactory oral formulation remains a challenge. Among the possible strategies to improve the absorption of drugs, micro- and nanoparticles represent an exciting approach to enhance the uptake and transport of orally administered molecules. Increasing attention has been paid to their potential use as carriers for peptide drugs for oral administration. This article reviews the most common manufacturing methods for polymeric particles and the physiology of particle absorption from the gastrointestinal (GI) tract. In a second part, the use of polymeric particulate systems to improve the oral absorption of insulin is discussed.
Fragrance Release from the Surface of Branched Poly (Amide) S
Authors: Aulenta F. , Drew M. , Foster A. , Hayes W. , Rannard S. , Thornthwaite D. , Youngs T.
Published: October 2008

Enzymes are powerful tools in organic synthesis that are able to catalyse a wide variety of selective chemical transformations under mild and environmentally friendly conditions. Enzymes such as the lipases have also found applications in the synthesis and degradation of polymeric materials. However, the use of these natural catalysts in the synthesis and the post-synthetic modification of dendrimers and hyperbranched molecules is an application of chemistry yet to be explored extensively. In this study the use of two hydrolytic enzymes, a lipase from Candida cylindracea and a cutinase from Fusarium solani pisii, were investigated in the selective cleavage of ester groups situated on the peripheral layer of two families of branched polyamides. These branched polyamides were conjugated to simple fragrances citronellol and L-menthol via ester linkages. Hydrolysis of the ester linkage between the fragrances and the branched polyamide support was carried out in aqueous buffered systems at slightly basic pH values under the optimum operative conditions for the enzymes used. These preliminary qualitative investigations revealed that partial cleavage of the ester functionalities from the branched polyamide support had occurred. However, the ability of the enzymes to interact with the substrates decreased considerably as the branching density, the rigidity of the structure and the bulkiness of the polyamide-fragrance conjugates increased.
Synthesis of PLA-b-PEG Multiblock Copolymers for Stealth Drug Carrier Preparation
Authors: Quesnel R. , Hildgen P.
Published: October 2008

An efficient method of preparing biodegradable and biocompatible multiblock copolymers from lactic acid and polyethylene glycol is proposed.
AFM study of a New Carrier Based on PLA and Salen Copolymers for Gene Therapy
Authors: Nadeau V. , Hildgen P.
Published: October 2008

The aim of this study was to synthesize novel biodegradable charged polymers to be used in DNA complexation for genetic delivery in different diseases. A new copolymer of PLA and complexed Schiff bases was synthesized in a several steps. This copolymer will be used as a nanocarrier. Also, AFM comparative studies in tapping mode were performed; on cationic copolymer and on PLA-Schiff base copolymer, on non-oriented and oriented film and on the DNA-cationic complex. The results indicated a difference in the topology and on phase picture of AFM film with or without cationic charge.
Covalent Polymer-Drug Conjugates
Authors: Elvira C. , Gallardo A. , Roman J. , Cifuentes A.
Published: October 2008

In this work, polymer-drugs conjugates used as drug delivery systems (DDS) are revised attending to their chemical conjugation. Namely, the classification of this type of DDS is based on the conjugation sites of the reactive groups (i.e., via end groups or pendant polymer groups). Advantages and limitations of these types of DDS are discussed through representative examples of polymer-drugs and polymer-proteins conjugates recently developed.
Bioadhesive Properties of Gantrez Nanoparticles
Authors: Irache Juan M. , Huici María , Konecny Monica , Espuelas Socorro , Campanero Miguel Angel , Arbos Pau
Published: October 2008

Bioadhesive nanoparticles have been proposed as carriers for the oral delivery of poorly available drugs and facilitate the use of this route. This work summarises some experiments describing the bioadhesive potential of Gantrez nanoparticles fluorescently labeled with rhodamine B isothiocyanate. The adhesive potential of Gantrez was found to be stronger when folded as nanoparticles than in the solubilised form. Conventional nanoparticles displayed a tropism for the upper areas of the gastrointestinal tract, with a maximum of adhesion 30 min post-administration and a decrease in the adhered fraction along the time depending on the given dose. The cross-linkage of nanoparticles with increasing amounts of 1,3-diaminopropane stabilised the resulting carriers and prolonged their half-life in an aqueous environment; although, the adhesive capacity of nanoparticles, the intensity and the relative duration of the adhesive interactions within the gut as a function of the cross-linking degree. Finally, nanoparticles were coated with either gelatin or albumin. In the first case, the presence of gelatin dramatically decreased the initial capacity of these carriers to interact with the gut mucosa and the intensity of these phenomenons. In the latter, bovine serum albumin coated nanoparticles (BSA-NP) showed an important tropism for the stomach mucosa without further significant distribution to other parts of the gut mucosa.
Biodegradable Polymers for Microencapsulation of Drugs
Authors: Park J. , Ye M. , Park K.
Published: October 2008

Drug delivery has become increasingly important mainly due to the awareness of the difficulties associated with a variety of old and new drugs. Of the many polymeric drug delivery systems, biodegradable polymers have been used widely as drug delivery systems because of their biocompatibility and biodegradability. The majority of biodegradable polymers have been used in the form of microparticles, from which the incorporated drug is released to the environment in a controlled manner. The factors responsible for controlling the drug release rate are physicochemical properties of drugs, degradation rate of polymers, and the morphology and size of microparticles. This review discusses the conventional and recent technologies for microencapsulation of the drugs using biodegradable polymers. In addition, this review presents characteristics and degradation behaviors of biodegradable polymers which are currently used in drug delivery.
Optimization of Protein Therapies by Polymer-Conjugation as an Effective DDS
Authors: Shibata Hiroko , Nakagawa Shinsaku , Tsutsumi Yasuo
Published: October 2008

Due to recent advances in disease proteomics, many disease-related proteins have been found. It is expected that there will be therapeutically useful proteins among them. However, it is clinically difficult to use most proteins as effective and safe drugs because of their very low stability and pleiotropic actions in vivo. To promote disease proteomic based drug development for protein therapies, we have attempted to develop an optimal polymer-conjugation system for improving the therapeutic potency of proteins. In this review, we introduce this innovative protein-drug system.
Hypervalent Iodine
Authors: Kotali Antigoni
Published: October 2008

Iodine was discovered in 1811 by French chemist Bernard Courtois and it was named by J. L. Gay Lussac in 1813.[...]
Stereoselective Synthesis of 5-7 membered Cyclic Ethers by Deiodonative Ring-Enlargement Using Hypervalent Iodine Reagents
Authors: Abo Tomohito , Sawaguchi Masanori , Senboku Hisanori , Hara Shoji
Published: October 2008

Stereoselective synthesis of 5-7 membered cyclic ethers was achieved by deiodonative ring-enlargement of cyclic ethers having an iodoalkyl substituent. The reaction took place readily under mild conditions using hypervalent iodine compounds and an acetoxy or a trifluoroacetoxy group was introduced into the rings depending on the hypervalent iodine reagent employed. The use of hexafluoroisopropanol (HFIP) as solvent is critical.
Easy and Safe Preparations of (Diacetoxyiodo) arenes from Iodoarenes, with Urea-Hydrogen Peroxide Adduct (UHP) as the Oxidant and the Fully Interpreted 1H- and 13C-NMR Spectra of the Products
Authors: Zielinska Agnieszka , Skulski Lech
Published: October 2008

An easy and safe, though only moderately effective method is presented forpreparing (diacetoxyiodo)arenes, ArI(OAc)2, from iodoarenes, ArI, using thecommercially available and easily handled urea-hydrogen peroxide adduct (UHP) as theoxidant. The reactions take place in anhydrous AcOH/Ac2O/AcONa (a catalyst)mixtures, at 40 oC for 3.5 h to afford the purified ArI(OAc)2 in 37-78% yields. The fullyinterpreted 1H- and 13C-NMR spectra of the ArI(OAc)2 products are reported.
Addition to Electron Deficient Olefins of α-Oxy Carbon- Centered Radicals, Generated from Cyclic Ethers and Acetals by the Reaction with Alkylperoxy- λ3-iodane
Authors: Sueda T. , Takeuchi Y. , Suefuji T. , Ochiai M.
Published: October 2008

Thermal decomposition of 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in cyclic ethers and acetals at 50 °C generates α-oxy carbon-centered radicals, which undergo an addition reaction with vinyl sulfones and unsaturated esters.
Oxidative Dearomatization of Phenols and Anilines via λ3- and λ5-Iodane-Mediated Phenylation and Oxygenation
Authors: Quideau S. , Pouységu L. , Ozanne A. , Gagnepain J.
Published: October 2008

Treatment of 2-methylphenols with chloro(diphenyl)-λ3-iodane led to theirregioselective dearomatizing 2-phenylation into cyclohexa-2,4-dienone derivatives via aproposed ligand coupling reaction. In the same vein of investigation, treatment of2-methylanilines with the λ5-iodane 2-iodoxybenzoic acid IBX reagent led to theirregioselective dearomatization into previously undescribed ortho-quinol imines.
Application of [Hydroxy(tosyloxy)iodo]benzene in the Wittig-Ring Expansion Sequence for the Synthesis of β-Benzocyclo-alkenones from α-Benzocycloalkenones
Authors: Justik M. , Koser G.
Published: October 2008

The conversion of α-benzocycloalkenones to homologous β-benzocyclo-alkenones containing six, seven and eight-membered rings is reported. This wasaccomplished via a Wittig olefination-oxidative rearrangement sequence using[hydroxy(tosyloxy)iodo]-benzene (HTIB) is the oxidant, that enables the synthesis ofregioisomeric pairs of methyl-substituted β-benzocycloalkenones. The incorporation ofcarbon-13 at C-1 of the β-tetralone nucleus was also demonstrated. The Wittig-HTIBapproach is a useful alternative to analogous sequences in which Tl(NO3)3·3H2O or thePrevost combination (AgNO3/I2) are employed in the oxidation step.
A Survey on the Reactivity of Phenyliodonium Ylide of 2-Hydroxy-1,4-Naphthoquinone with Amino Compounds
Authors: Spagou Konstantina , Malamidou-Xenikaki Elizabeth , Spyroudis Spyros
Published: October 2008

The phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone reacts with aminoesters, ureas, aminoalcohols and aminophenols in refluxing dichloromethane to afford good yields of indanedione 2-carboxamido compounds, that in solution exist in an enol-amide form. The same reactants in a copper-catalyzed reaction afford mainly the corresponding N-arylo compounds. Arylhydrazines are mainly oxidized by the ylide and arylation occurs only in a low yield.
Pd-Catalyzed Carbonyl Insertion Coupling Reactions of a Hypervalent Iodoheterocycle with Alcohols and Amines
Authors: Luo Shengj-Jun , Ma Yong-Xiang , Liang Yong-Min
Published: October 2008

The palladium-catalyzed cross-coupling carbonyl insertion reaction between 3,7-bis(N,N-dimethylamino)-10H-dibenz[b,e]iodinium iodide (1) and alcohols or amines 2 is described. Some new amides and esters 3 containing an active iodo functional group have been prepared in 65-91% yields.
Substrate Dependence in Aqueous Diels-Alder Reactions of Cyclohexadiene Derivatives with 1,4-Benzoquinone
Authors: Sunakawa Takeshi , Kuroda Chiaki
Published: October 2008

A reactivity difference based on the position of substituents on cyclohexa-1,3- diene was observed for the title reaction. The effect of water as solvent was more distinct for 1-methyl-4-isopropylcyclohexa-1,3-diene than for 2-methyl-5-isopropylcyclohexa- 1,3-diene or non-substituted cyclohexa-1,3-diene. The effect of NaCl (salting-out) and guanidium chloride (salting-in) was also large for 1-methyl-4-isopropylcyclohexa-1,3- diene.
Synthesis and Molecular Structure of Methyl 4-O-methyl-α-D-glucopyranuronate
Authors: Hirsch Ján , Langer Vratislav , Koóš Miroslav
Published: October 2008

A method for the preparation of methyl 4-O-methyl-α-D-glucopyranuronate andits single crystal X-ray structure determination are reported. The molecule adopts an almostideal 4C1 (OC3) conformation.
Synthesis of the Key Precursor of Hirsutellide A
Authors: Xu Yanjie , Duan Xuemin , Li Meiling , Jiang Liqin , Zhao Guangle , Meng Yi , Chen Ligong
Published: October 2008

Hexadepsipeptide 2, the precursor of Hirsutellide A (1), was synthesized in an overall yield of 45% from N-Boc-Me-Gly via three coupling reactions using dicyclohexylcarbodiimide (DCC), O-(7-azabenzotriazol-1-yl)-N,N,N’,N’-tetramethyl- uronium hexafluorophosphate (HATU) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl), respectively.
Synthesis of Unsymmetrical Annulated 2,2’-Bipyridine Analogues with Attached Cycloalkene and Piperidine Rings via Sequential Diels-Alder Reaction of 5,5’-bi-1,2,4-triazines
Authors: Branowska D.
Published: October 2008

Synthesis of bisfunctionalized unsymmetrical 2,2’-bipyridines 8 or their sulfonyl derivatives 12a,b are described. They were prepared via the Diels-Alder reaction of 1-methyl-4-pyrrolidin-1-yl-1,2,3,6-tetrahydropyridine (6) with 3,3’-bis(methyl- sulfanyl)-5,5’-bi-1,2,4-triazine (1). The reaction leads to the single cycloaddition product 7 which undergoes Diels-Alder reaction with cyclic enamines 2a,b to give unsymmetrical 2,2’-bipyridine derivatives 8, consisting of the two different heterocyclic units: cycloalkeno[c]pyridine and 2,6-naphthyridine.
A Direct Route to 6,6’-Disubstituted-2,2’-Bipyridines by Double Diels-Alder/retro Diels-Alder Reaction of 5,5’-bi-1,2,4-Triazines
Authors: Branowska D.
Published: October 2008

Inverse electron demand Diels-Alder reaction of functionalized 5,5’-bi-1,2,4- triazines with bicyclo[2.2.1]hepta-2,5-diene in boiling p-cymene leads to a range of 6,6’- disubstituted-2,2’-bipyridines in good yield.
Chemical and Photochemical Synthesis of Substituted Dihydro-thieno[2',3':4,5]thieno[2,3-c]quinolin-6-ones and Tetrahydro-dithieno[2,3-b:2',3'-d]thieno[2'',3''c:2'',3''c’]diquinolin-6,14-dione
Authors: Šafarik Jelena , Koružnjak Jasna , Karminski-Zamola Grace
Published: October 2008

Some new substituted dihydrothieno[2',3':4,5]thieno[2,3-c]quinolin-6-ones 9- 12 and tetrahydrodithieno[2,3-b: 2',3'-d]thieno[2'',3''-c:2'',3''-c’]diquinolin-6,14-dione (17) were prepared from the corresponding new anilides 5-8 and from the corresponding dianilide 15, respectively, by a multistep combination of chemical and photochemical reactions. All the prepared compounds are of particular interest because they might serve as DNA intercalators in anticancer therapy.
An Electron Transfer Approach to the Preparation of Highly Functionalized Anthraquinones
Authors: Beziane Abdelouahab , Terme Thierry , Vanelle Patrice
Published: October 2008

A series of highly functionalized quinones was prepared by an original reaction of 2,3-bis(chloromethyl)-1,4-dimethoxyanthraquinone (6) with various nitronate anions under electron transfer reaction conditions.
Synthesis of Analogs of Amathamide A and Their Preliminary Antimicrobial Activity
Authors: Ramírez-Osuna M. , Chávez D. , Hernández L. , Molins E. , Somanathan R. , Aguirre G.
Published: October 2008

Syntheses of three non-brominated analogs of amathamide A (1), a natural alkaloid isolated from the Tasmanian marine bryozoan Amathia wilsoni, are described. Antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomona aeruginosa, and Candida albicans was tested. Test results for amathamide A (1) showed a weak activity against C. albicans and E. coli. The three non-natural analogs 2-4 proved to be inactive compounds.
Syntheses, Characterization and Study of the Use of Cobalt (II) Schiff–Base Complexes as Catalysts for the Oxidation of Styrene by Molecular Oxygen
Authors: Khandar Ali Akbar , Nejati Kamellia , Rezvani Zolfaghar
Published: October 2008

Schiff-Base complexes of bis-5-phenylazosalicylaldehyde ethylenediimine and bis-5-phenylazosalicylaldehyde-O-phenylenediimine ligands with Co(II) (I and II) have been synthesized and characterized by their IR spectra and elemental analyses. These complexes catalyze the oxidation of styrene in the presence of dioxygen and excess pyridine. The effect of the reaction conditions on the oxidation of styrene was studied by varying solvent, nature and amount of the catalyst and substrate. The catalytic behavior of the studied complexes was shown to be dependent on the conditions applied. In all reactions, acetophenone and 1- phenylethanol were the only observed products.
Asymmetric Synthesis of Double Bond Isomers of the Structure Proposed for Pyrinodemin A and Indication of Its Structural Revision
Authors: Ishiyama Haruaki , Tsuda Masashi , Endo Tadashi , Kobayashi Jun’ichi
Published: October 2008

Asymmetric synthesis of double bond isomers ( )-2 (∆15’,16’) and ( )-3 (∆14’,15’) ofthe structure (1) (∆16’,17’) proposed for pyrinodemin A, a cytotoxic bis-pyridine alkaloidwith a unique cis-cyclopent[c]isoxazolidine moiety from a marine sponge, has beenaccomplished. Pyrinodemin A was indicated to be a 1:1 racemic mixture of 2 fromcomparison of C18 and chiral HPLC analysis for pyrinodemin A and the syntheticcompounds as well as ESIMS data of oxidative degradation products of pyrinodemin A.
Publication Note Concerning Molecules 2002, 7, 717-720
Authors: McPhee Derek
Published: October 2008

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Sulfur-Nitrogen Heterocycles
Authors: García-Valverde Maria , Torroba Tomás
Published: October 2008

For more than a century, heterocycles have constituted one the largest areas of research in organic chemistry.[...]
1,3-Dipolar Cycloaddition Reactions of 1-(4-Phenylphenacyl)-1,10-phenanthrolinium N-Ylide with Activated Alkynes and Alkenes
Authors: Dumitrascu F. , Caira M. R. , Draghici C. , Caproiu M. T. , Badoiu A.
Published: October 2008

The 3 2 cycloaddition reaction of 1-(4-phenylphenacyl)-1,10-phenanthrolinium ylide with activated alkynes gave pyrrolo[1,2- 4a][1,10]phenanthrolines 6a-d. The "one pot" synthesis of 6a,b,d from 4, activatedalkenes, Et3N and tetrakis-pyridine cobalt (II) dichromate (TPCD) is described. Thehelical chirality of pyrrolophenanthrolines 6b-d was put in evidence by NMRspectroscopy.