bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Postmenopausal Osteoporosis: Focus on Strontium Ranelate
Authors: Cortet Bernard
Published: February 2011

Given its increasing incidence and serious complications, osteoporosis requires safe and effective long-term treatment. Strontium ranelate (SR), a new anti-osteoporotic treatment with a unique mode of action, has been investigated in the Spinal Osteoporosis Therapeutic Intervention (SOTI) and the Treatment Of Peripheral OSteoporosis (TROPOS) trials, two major 3-year multinational placebo-controlled Phase III randomized clinical trials. In SOTI, SR treatment reduced the risk of vertebral fracture by 41% (20.9% vs. 32.8%, P < 0.001); in TROPOS, it reduced the risk of non-vertebral fracture by 16% (11.2% vs. 12.9%, P = 0.04), and the risk of hip fracture in patients at high risk by 36% (4.3% vs. 6.4%, P = 0.046). Also SR has been shown to decrease the risk of vertebral fracture after 4 years of treatment and the risk of nonvertebral fracture after 5 years. Also it demonstrated for high risk patients a significant decrease of the risk of hip fractures (–43%) after 5 years of treatment. Unlike antiresorptive agents, SR produced steady and significant BMD increases that correlated directly with decreases in vertebral and hip fracture risk. Preplanned analysis of the pooled dataset from SOTI and TROPOS showed that SR was effective whether or not patients had key risk factors for fractures at baseline. SR was also effective in patients with osteopenia and younger postmenopausal patients aged 50–65 years. It was also effective for preventing both vertebral and nonvertebral fractures in the elderly (>80 years). Also, SR significantly attenuated height loss and decreased back pain. Finally long-term follow-up showed that BMD gains were maintained through a 8 year-period with maintaining the incidence of fracture between the first 3 years and the last 3 years of treatment. The safety profile of SR was almost similar to placebo in both trials. A slight but significant increased risk of thromboembolism events was noted from the pooled phase III studies data. However this increased was not found in a large retrospective observational study. Thus, SR demonstrates broad spectrum safety and efficacy in reducing the risks of both vertebral and non-vertebral (including hip) fractures in a wide variety of patients, and should be considered as a first-line option to treat women at risk of osteoporotic fractures, whatever their age, the severity of the disease, and their risk factors.
Deep silicon maxima in the stratified oligotrophic Mediterranean Sea
Authors: Crombet Y. , Leblanc K. , Quéguiner B. , Moutin T. , Rimmelin P. , Ras J. , Claustre H. , Leblond N. , Oriol L. , Pujo-Pay M.
Published: February 2011

Abstract. The silicon biogeochemical cycle has been studied in the Mediterranean Sea during late summer/early autumn 1999 and summer 2008. The distribution of nutrients, particulate carbon and silicon, fucoxanthin (Fuco), and total chlorophyll-a (TChl-a) were investigated along an eastward gradient of oligotrophy during two cruises (PROSOPE and BOUM) encompassing the entire Mediterranean Sea during the stratified period. At both seasons, surface waters were depleted in nutrients and the nutriclines gradually deepened towards the East, the phosphacline being the deepest in the easternmost Levantine basin. Following the nutriclines, parallel deep maxima of biogenic silica (DSM), fucoxanthin (DFM) and TChl-a (DCM) were evidenced during both seasons with maximal concentrations of 0.45 μmol L−1 for BSi, 0.26 μg L−1 for Fuco, and 1.70 μg L−1 for TChl-a, all measured during summer. Contrary to the DCM which was a persistent feature in the Mediterranean Sea, the DSM and DFMs were observed in discrete areas of the Alboran Sea, the Algero-Provencal basin, the Ionian sea and the Levantine basin, indicating that diatoms were able to grow at depth and dominate the DCM under specific conditions. Diatom assemblages were dominated by Chaetoceros spp., Leptocylindrus spp., Pseudonitzschia spp. and the association between large centric diatoms (Hemiaulus hauckii and Rhizosolenia styliformis) and the cyanobacterium Richelia intracellularis was observed at nearly all sites. The diatom's ability to grow at depth is commonly observed in other oligotrophic regions and could play a major role in ecosystem productivity and carbon export to depth. Contrary to the common view that Si and siliceous phytoplankton are not major components of the Mediterranean biogeochemistry, we suggest here that diatoms, by persisting at depth during the stratified period, could contribute to a large part of the marine primary production as observed in other oligotrophic areas.
Soil temperature response to 21st century global warming: the role of and some implications for peat carbon in thawing permafrost soils in North America
Authors: Wisser D. , Marchenko S. , Talbot J. , Treat C. , Frolking S.
Published: February 2011

Abstract. Northern peatlands contain a large terrestrial carbon pool that plays an important role in the Earth's carbon cycle. A considerable fraction of this carbon pool is currently in permafrost and is biogeochemically relatively inert; this will change with increasing soil temperatures as a result of climate warming in the 21st century. We use a geospatially explicit representation of peat areas and peat depth from a recently-compiled database and a geothermal model to estimate northern North America soil temperature responses to predicted changes in air temperature. We find that, despite a widespread decline in the areas classified as permafrost, soil temperatures in peatlands respond more slowly to increases in air temperature owing to the insulating properties of peat. We estimate that an additional 670 km3 of peat soils in North America, containing ~33 Pg C, could be seasonally thawed by the end of the century, representing ~20% of the total peat volume in Alaska and Canada. Warming conditions result in a lengthening of the soil thaw period by ~40 days, averaged over the model domain. These changes have potentially important implications for the carbon balance of peat soils.
Case Study: First Implantation of a Frozen, Devitalized Tissue-engineered Vascular Graft for Urgent Hemodialysis Access
Authors: Wystrychowski Wojciech , Cierpka Lech , Zagalski Krzysztof , Garrido Sergio , Dusserre Nathalie , Radochonski Sam , McAllister Todd N. , L'Heureux Nicolas
Published: February 2011

Previously we reported on the mid- to long-term follow-up in the first clinical trial to use a completely autologous tissue-engineered graft in the high pressure circulation. In these early studies, living grafts were built from autologous fibroblasts and endothelial cells obtained from small skin and vein biopsies. The graft was assembled using a technique called tissue-engineering by self-assembly (TESA), where robust conduits were grown without support from exogenous biomaterials or synthetic scaffolding. One limitation with this earlier work was the long lead times required to build the completely autologous vascular graft. Here we report the first implant of a frozen, devitalized, completely autologous Lifeline™ vascular graft. In a departure from previous studies, the entire fibroblast layer, which provides the mechanical backbone of the graft, was air-dried then stored at −80°C until shortly before implant. Five days prior to implant, the devitalized conduit was rehydrated, and its lumen was seeded with living autologous endothelial cells to provide an antithrombogenic lining. The graft was implanted as an arteriovenous shunt between the brachial artery and the axillary vein in a patient who was dependent upon a semipermanent dialysis catheter placed in the femoral vein. Eight weeks postoperatively, the graft functions without complication. This strategy of preemptive skin and vein biopsy and cold-preserving autologous tissue allows the immediate availability of an autologous arteriovenous fistula, and is an important step forward in our strategy to provide allogeneic tissue-engineered grafts available “off-the-shelf”.
Quantitative Amino Acid Analysis
Authors: Rutherfurd Shane M. , Dunn Benn M.
Published: February 2011

Quantitative amino acid analysis is an important tool for many scientific areas ranging from the characterization of recombinant proteins to the description of food proteins for nutritional assessment. Quantitative amino acid analysis is often overlooked in many laboratories due to the difficulties involved in obtaining reliable amino acid composition data. Fortunately, for protein chemists, the creation of protein chemistry core laboratories devoted mainly to protein sequence analysis and peptide synthesis has provided new instrumentation that yields the necessary precision. In addition, for food scientists, it has become clear that for the description of food proteins, the nitrogen content alone simply does not provide sufficient information about the nutritional adequacy of these proteins, and as a result, a growing number of nutrition laboratories are undertaking amino acid analysis. This unit describes the information that can be derived from quantitative amino acid analysis and gives examples of the calculations that are needed. Curr. Protoc. Protein Sci. 63:3.2.1‐3.2.6. © 2011 by John Wiley & Sons, Inc.
Site‐saturation Mutagenesis: A Powerful Tool for Structure‐Based Design of Combinatorial Mutation Libraries
Authors: Chronopoulou Evangelia G. , Labrou Nikolaos E.
Published: February 2011

This unit describes a method for site‐saturation mutagenesis (SSM) using PCR amplification with degenerate synthetic oligonucleotides as primers. SSM allows the substitution of predetermined protein sites against all twenty possible amino acids at once. Therefore, SSM is a powerful approach in protein engineering to characterize structure‐function relationships, as well as to create improved protein variants. The procedure accepts double‐stranded plasmid isolated from the dam+ E. coli strain. The procedure is simple, fast, efficient, and eliminates time‐consuming subcloning and ligation steps. Curr. Protoc. Protein Sci. 63:26.6.1‐26.6.10. © 2011 by John Wiley & Sons, Inc.
Post‐polymerization crosslinked polyurethane shape memory polymers
Authors: Hearon Keith , Gall Ken , Ware Taylor , Maitland Duncan J. , Bearinger Jane P. , Wilson Thomas S.
Published: February 2011

Novel urethane post‐polymerization curable shape memory polymers (SMPs) have been synthesized and characterized. Several series of linear, olefinic urethane polymers were made from 2‐butene‐1,4‐diol, other saturated diols, and various aliphatic diisocyanates. These thermoplastics were melt‐processed into desired geometries and thermally crosslinked at 200°C or radiation crosslinked at 50 kGy. The SMPs were characterized by solvent swelling and extraction, differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), tensile testing, and qualitative shape recovery analysis. Swelling and DMA results provided concrete evidence of chemical crosslinking, and further characterization revealed that the urethanes had outstanding mechanical properties. Key properties include tailorable transitions between 25 and 80°C, tailorable rubbery moduli between 0.2 and 4.2 MPa, recoverable strains approaching 100%, failure strains of over 500% at Tg, and qualitative shape recovery times of less than 12 s at body temperature (37°C). Because of its outstanding thermo‐mechanical properties, one polyurethane was selected for implementation in the design of a complex medical device. We believe that these new post‐polymerization crosslinkable urethane SMPs are an industrially relevant class of highly processable shape memory materials. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Structure and thermal stability of polysaccharide fractions extracted from the ultrasonic irradiated and cold alkali pretreated bamboo
Authors: Li Ming‐Fei , Fan Yong‐Ming , Xu Feng , Sun Run‐Cang
Published: February 2011

Polysaccharide fractions were extracted from partially delignified bamboo (Neosinocalamus affinis) culms pretreated with ultrasonic irradiation for varied times and cold sodium hydroxide/urea solution, and their structure and thermal stability were comparatively characterized. In this case, ball‐milled bamboo culms were treated with ultrasonic irradiation for varied times (0, 5, 15, and 25 min), dissolved with 7% sodium hydroxide/12% urea solution at −12°C, and then extracted with ethanol and dioxane to obtain partially delignified solid fractions. Subsequently, the solid fractions were subjected to be extracted with dimethyl sulfoxide followed by precipitation in ethanol and yielded the polysaccharide fractions. Sugar analysis indicated that the total sugar content increased from 60.63% in the polysaccharide fraction prepared without ultrasonic irradiation to 81.26% in the polysaccharide fraction prepared with an ultrasonic irradiation time of 25 min. Glucose (∼ 50–55%) was the major sugar component, and xylose (∼ 41–44%) was the second major sugar in polysaccharide fractions in all cases. Spectroscopy (FTIR, 1H‐NMR, 13C‐NMR, and HSQC) analysis suggested that the polysaccharide fractions were mainly composed of (1→4)‐linked α‐D‐glucan from amylose and (1→4)‐linked β‐D‐xylan attached with minor amounts of branched sugars from hemicelluloses. In addition, thermal analysis showed that the main degradation stage of the polysaccharide fractions occurred between 210 and 320°C. Compared to the polysaccharide fraction prepared without ultrasonic irradiation, the polysaccharide fraction prepared with ultrasonic irradiation had a slightly lower thermal stability. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Hyperbranched polymer based on triphenylamine and pyridine: Fluorescent chemosensors for palladium ions
Authors: Feng Jichang , Zhang Cong , Li Yang , Yang Mujie
Published: February 2011

Two new hyperbranched fluorescent conjugated polymers containing pyridine units were synthesized via Heck coupling reaction and Sonogashira coupling reaction, respectively, and characterized by 1H NMR, 13C NMR, FTIR, and GPC. The copolymers are readily soluble in common organic solvents such as chloroform, THF, and DMF. Thermal analysis revealed that the copolymers had good thermal stability. The fluorescence quenching behaviors of the hyperbranched copolymers by metal ions were studied. It was found that the fluorescence of the copolymers can be effectively quenched by Pd2+. Moreover, the two hyperbranched copolymers exhibited different quenching efficiency, which may be related to difference in the hindrance for the chelation of pyridine unit with metal ions of the two polymers. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Luminescent properties of long‐lasting BaAlxOy:Eu2+,Dy3+ nanocomposites
Authors: Bem Daniel B. , Swart Hendrick C. , Luyt Adriaan S. , Dejene Francis B.
Published: February 2011

BaAlxOy:Eu2+,Dy3+ blue‐green phosphor samples were synthesized by a combustion method at the low temperature of 500°C. Phosphor nanocrystallites with high brightness were obtained without significantly changing the crystalline structure of the host. The crystallite sizes determined from the Scherrer equation ranged between 34 and 41 nm. Different volume fractions of the BaAlxOy:Eu2+,Dy3+ powder were then introduced in LDPE polymer. The resulting composites were similarly analyzed and also thermally characterized by means of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). PL results indicate that the LDPE‐phosphor interface, which is considered to have an influence on the composite behavior, did not significantly change the spectral positions of the phosphor materials, whose major emission peaks occurred at about 505 nm. The improved afterglow results for the composites may have been caused by morphological changes due to increased surface area and defects. Thermal results indicate that the BaAlxOy:Eu2+,Dy3+ particles acted as nucleating centers and enhanced the overall crystallinity in the LDPE nanocomposite while preventing lamellar growth, hence reducing the crystallite sizes in LDPE. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Studies on Fourier transform infrared spectroscopy, scanning electron microscope, and direct current conductivity of polyaniline doped zinc ferrite
Authors: Patil Ramesh , Roy Aashis S. , Anilkumar Koppalkar R. , Ekhelikar Srikant
Published: February 2011

In situ polymerization of aniline was carried out in the presence of zinc ferrite to synthesize polyaniline/ZnFe2O4 composites (PANI/ZnFe2O4) by chemical oxidation method. The composites have been synthesized with various compositions (10, 20, 30, 40, and 50 wt %) of zinc ferrite in PANI. From the Fourier transform infrared spectroscopy (FTIR) studies on polyaniline/ZnFe2O4 composites, the peak at 1140 cm−1 is considered to be measure of the degree of electron delocalization. The surface morphology of these composites was studied with scanning electron micrograph (SEM). The dc conductivity has been studied in the temperature range from 40–160°C and supports the one‐dimensional variable range hopping (1DVRH) model proposed by Mott. The results obtained for these composites are of scientific and technological interest. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Effect of methacrylic acid on the properties of Ethylene–Vinylene acetate rubber vulcanizates reinforced by magnesium hydroxide
Authors: Yu Haiyang , Zhang Yong , Ren Wentan , Chen Shuguo , Hoch Martin , Guo Sharon
Published: February 2011

Ethylene–vinyl acetate rubber (EVM) vulcanizates with excellent mechanical properties were obtained with magnesium hydroxides (MH) and methacrylic acid (MAA). MAA significantly improved the mechanical properties of the MH‐filled EVM vulcanizates. The tensile strength, Shore A hardness, and tensile set modulus of the EVM vulcanizates significantly increased with increasing MAA content. The tensile strength of the MH‐filled EVM vulcanizates increased from 12.3 to 18.5 MPa after the addition of 2.5 phr MAA when the MH content was fixed at 60 phr. The gross crosslink density and ionic crosslink density increased with increasing MAA content. The glass‐transition temperature and tan δ slightly decreased with increasing MAA content. Morphological study showed that MAA obviously improved the dispersion of the MH particles in the EVM matrix. The thermal stability of the EVM vulcanizates was obviously enhanced after the addition of MAA. Fourier transform infrared analysis indicated that MAA reacted with MH to form magnesium methacrylates, and there was a polymerization of MAA during the curing process in the existence of peroxide. An ionic crosslink bond was thought to be formed on the surface of the MH aggregates; this resulted in a possible structure where MH aggregates were considered as crosslink points. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Effect of titanium dioxide on the flame‐retardant finishing of cotton fabric
Authors: Lam Y. L. , Kan C. W. , Yuen C. W. M.
Published: February 2011

In this study, titanium dioxide (TiO2) or nano titanium dioxide (nano‐TiO2) was used as a cocatalyst in the flame‐retardant (FR) formulation of N‐methylol dimethylphosphonopropionamide (Pyrovatex CP New, FR), melamine resin [Knittex CHN, crosslinking agent (CL)], and phosphoric acid (PA) for cotton fabrics to improve the treatment effectiveness and minimize the side effects of the treatment. For FR‐treated cotton fabrics, the flame extinguished right after removal of the ignition source with no flame spreading. However, after neutralization and/or home laundering, FR–CL‐treated specimens failed the flammability test, whereas the opposite results were obtained from FR–CL–PA‐treated specimens. A noticeable result was that the TiO2/nano‐TiO2 cocatalyst had a significant effect on decreasing the flame‐spread rate. Thermal analysis found that the FR‐treated specimens without wet posttreatment showed two endothermic peaks representing the phosphorylation of cellulose and acid‐catalyzed dehydration. In addition, the treated fabrics showed some new characteristic peaks in their chemical structures; these were interpreted as carbonyl bands, CH2 rocking bands, and CH3 asymmetric and CH2 symmetric stretching. The surface morphology of the FR–CL–PA‐treated cotton specimens showed a roughened and wrinkled fabric surface with a high deposition of the finishing agent that had a lower breaking load and tearing strength, which resulted from the side effects of the CL used. However, the addition of a TiO2 or nano‐TiO2 cocatalyst could compensate for the reduction in the tensile strength. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Shelf‐edge reefs as priority areas for conservation of reef fish diversity in the tropical Atlantic
Authors: Olavo George , Costa Paulo A. S. , Martins Agnaldo S. , Ferreira Beatrice P.
Published: February 2011

Data from fishing surveys employing bottom long‐lines were analysed to characterize the diversity, assemblages and distribution patterns of demersal fish along the Brazilian outer shelf and upper slope, between latitudes 13°S and 22°S.

Non‐metric multi‐dimensional scaling (MDS) and cluster analysis indicate three distinct species assemblages separated primarily by depth (the 200 m isobath) and secondarily by latitude (19°S), suggesting a continual transition along the depth and latitudinal gradients in the study area. Species richness was negatively correlated with depth, but with no clear relationship with latitude.

Results suggest the existence of reef formations on the shelf‐edge zone (40–200 m) and slope down to 500 m depth off the eastern Brazilian coast. More than 75% of the catches recorded were reef fish species from the families Serranidae, Lutjanidae, Malacanthidae, Muraenidae, Sparidae, Balistidae, Carangidae, Haemulidae, Scorpaenidae and Priacanthidae.

The maximum depth of occurrence for 20 reef species was extended from limits previously recorded.

The findings reinforce the hypothesis of a faunal corridor for species associated with deep reef formations along the shelf‐edge zone (40–200 m), in the South American continental margin, connecting the south‐western Atlantic and the Caribbean provinces.

The shelf‐edge reefs support important multi‐species fisheries and harbour critical habitats for the life cycle of many reef fish species, including spawning aggregation sites that are extremely vulnerable to human pressures, such as intensive fishing, shipping and offshore oil and gas exploitation; all activities currently expanding off the Brazilian coast.

Results reveal the biological importance of deep shelf‐edge reefs as a critical ecological area. Despite their importance, shelf edge reefs are not currently included in any marine protected area network in the tropical south‐western Atlantic. There is now an urgent need to enhance knowledge, implement adequate management strategies and consider these deeper habitats as priority areas for conservation. Copyright © 2011 John Wiley & Sons, Ltd.
The design of smooth switching control with application to V/STOL aircraft dynamics under input and output constraints
Authors: Chen Pang‐Chia
Published: February 2011

This paper presents a smooth switching gain‐scheduled control approach for linear parameter varying (LPV) system dynamics, indexed by a scalar varying parameter. The proposed approach is demonstrated by application to the planar vertical/short takeoff and landing (V/STOL) aircraft dynamics subject to input and output constraints. In the design of switching control, the switch logic determines the switching process between control laws. The usual switching logics use the instantaneous switching manner, which can cause discontinuous chattering control signal. By performing convex weightings between two individual control laws for neighboring subsystems, the proposed smooth switching gain‐scheduled control approach can provide improved performance but does not arouse control signal chattering. For the studied application, the nonlinear aircraft dynamics are represented in the form of LPV systems with parameter dependence on attitude angle. The resulting design is verified by the obtained relative stability and time response simulations.

Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Estimation of the variances of TCP/RED using stochastic differential equation
Authors: Fan Hua , Ren Yong , Shan Xiuming
Published: February 2011

By using the stochastic differential equation (SDE), a model is built to describe the system behavior, especially the queue length behavior, of TCP/RED (transmission control protocol with random early detection) on a single bottleneck network. Then, not only the static equilibrium point of the system is calculated, but also its variance is estimated. After calculating the variance of the queue length in the router, the authors show how such random oscillation affects the maximum connection number that the link admits while keeping low dropping probability, and how this relation is influenced by other network parameters. This model can be applied to the case where only homogeneous TCP flows exist, as well as where TCP and UDP (user data protocol) flows coexist. The simulations by NS‐2 show that our deductive method is effective.

Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
The European wood pellet markets: current status and prospects for 2020
Authors: Sikkema Richard , Steiner Monika , Junginger Martin , Hiegl Wolfgang , Hansen Morten Tony , Faaij Andre
Published: February 2011

The wood pellet market is booming in Europe. The EU 2020 policy targets for renewable energy sources and greenhouse gas (GHG) emissions reduction are among the main drivers. The aim of this analysis is to map current European national wood pellet demand and supplies, to provide a comprehensive overview of major market types and prices, and to discuss the future outlook in light of raw material supply. Approximately 650 pellet plants produced more than 10 million tonnes of pellets in 2009 in Europe. Total European consumption was about 9.8 million tonnes, of which some 9.2 million tonnes is within the EU‐27, representing a modest 0.2% of Gross Energy Consumption (75 EJ level in 2008). The prices of most pellet types are increasing. While most markets of non‐industrial pellets are largely self‐sufficient, industrial pellet markets depend on the import of wood pellets from outside the EU‐27. Industrial pellet markets are relatively mature, compared to non‐industrial ones, because of their advanced storage facilities and long‐term price‐setting. However, industrial pellet markets are unstable, depending mainly on the establishment or the abolishment of public support schemes.

Following our scenarios, additional 2020 demand for woody biomass varies from 105 million tonnes, based on market forecasts for pellets in the energy sector and a reference growth of the forest sector, to 305 million tonnes, based on maximum demand in energy and transport sectors and a rapid growth of the forest sector. Additional supply of woody biomass may vary from 45 million tonnes from increased harvest levels to 400 million tonnes after the recovery of slash via altered forest management, the recovery of waste wood via recycling, and the establishment of woody energy plantations in the future. Any short‐term shortages within the EU‐27 may be bridged via imports from nearby regions such as north west Russia or overseas. © 2011 Society of Chemical Industry and John Wiley & Sons, Ltd
An overview of techniques for linking high‐dimensional molecular data to time‐to‐event endpoints by risk prediction models
Authors: Binder Harald , Porzelius Christine , Schumacher Martin
Published: February 2011

Analysis of molecular data promises identification of biomarkers for improving prognostic models, thus potentially enabling better patient management. For identifying such biomarkers, risk prediction models can be employed that link high‐dimensional molecular covariate data to a clinical endpoint. In low‐dimensional settings, a multitude of statistical techniques already exists for building such models, e.g. allowing for variable selection or for quantifying the added value of a new biomarker. We provide an overview of techniques for regularized estimation that transfer this toward high‐dimensional settings, with a focus on models for time‐to‐event endpoints. Techniques for incorporating specific covariate structure are discussed, as well as techniques for dealing with more complex endpoints. Employing gene expression data from patients with diffuse large B‐cell lymphoma, some typical modeling issues from low‐dimensional settings are illustrated in a high‐dimensional application. First, the performance of classical stepwise regression is compared to stagewise regression, as implemented by a componentwise likelihood‐based boosting approach. A second issues arises, when artificially transforming the response into a binary variable. The effects of the resulting loss of efficiency and potential bias in a high‐dimensional setting are illustrated, and a link to competing risks models is provided. Finally, we discuss conditions for adequately quantifying the added value of high‐dimensional gene expression measurements, both at the stage of model fitting and when performing evaluation.
Prospects for microbial biodiesel production
Authors: Shi Shuobo , Valle‐Rodríguez Juan Octavio , Siewers Verena , Nielsen Jens
Published: February 2011

As the demand for biofuels for transportation is increasing, it is necessary to develop technologies that will allow for low‐cost production of biodiesel. Conventional biodiesel is mainly produced from vegetable oil by chemical transesterification. This production, however, has relatively low land‐yield and is competing for agricultural land that can be used for food production. Therefore, there is an increasing interest in developing microbial fermentation processes for production of biodiesel as this will allow for the use of a wide range of raw‐materials, including sugar cane, corn, and biomass. Production of biodiesel by microbial fermentation can be divided into two different approaches, (1) indirect biodiesel production from oleaginous microbes by in vitro transesterification, and (2) direct biodiesel production from redesigned cell factories. This work reviews both microbial approaches for renewable biodiesel production and evaluates the existing challenges in these two strategies.
Engineering of Escherichia coli for targeted delivery of transgenes to HER2/neu‐positive tumor cells
Authors: Chang Chih‐Hsiang , Cheng Wei‐Jou , Chen Shan‐Yu , Kao Ming‐Ching , Chiang Chung‐Jen , Chao Yun‐Peng
Published: February 2011

Targeting of non‐phagocytic tumor cells and prompt release of gene cargos upon entry into tumors are two limiting steps in the bacterial gene delivery path. To tackle these problems, the non‐pathogenic Escherichia coli strain BL21(DE3) was engineered to display the anti‐HER2/neu affibody on the surface. After co‐incubation with tumor cells for 3 h, the anti‐HER2/neu affibody‐presenting E. coli strain was selectively internalized into HER2/neu‐positive SKBR‐3 cells. The invasion efficiency reached as high as 30%. Furthermore, the bacteria were equipped with the phage ϕX174 lysin gene E‐mediated autolysis system. Carrying the transgene (e.g., eukaryotic green fluorescent protein, GFP), the tumor‐targeting bacteria were subjected to the thermal shock to trigger the autolysis system upon entry into HER2/neu‐positive cells. Flow cytometric analysis revealed that 3% of infected cells expressed GFP 24 h post thermal induction. Overall, the results show a promise of the proposed approach for developing bacteria as a delivery carrier. Biotechnol. Bioeng. 2011; 108:1662–1672. © 2011 Wiley Periodicals, Inc.
Microscale to manufacturing scale‐up of cell‐free cytokine production—a new approach for shortening protein production development timelines
Authors: Zawada James F. , Yin Gang , Steiner Alexander R. , Yang Junhao , Naresh Alpana , Roy Sushmita M. , Gold Daniel S. , Heinsohn Henry G. , Murray Christopher J.
Published: February 2011

Engineering robust protein production and purification of correctly folded biotherapeutic proteins in cell‐based systems is often challenging due to the requirements for maintaining complex cellular networks for cell viability and the need to develop associated downstream processes that reproducibly yield biopharmaceutical products with high product quality. Here, we present an alternative Escherichia coli‐based open cell‐free synthesis (OCFS) system that is optimized for predictable high‐yield protein synthesis and folding at any scale with straightforward downstream purification processes. We describe how the linear scalability of OCFS allows rapid process optimization of parameters affecting extract activation, gene sequence optimization, and redox folding conditions for disulfide bond formation at microliter scales. Efficient and predictable high‐level protein production can then be achieved using batch processes in standard bioreactors. We show how a fully bioactive protein produced by OCFS from optimized frozen extract can be purified directly using a streamlined purification process that yields a biologically active cytokine, human granulocyte‐macrophage colony‐stimulating factor, produced at titers of 700 mg/L in 10 h. These results represent a milestone for in vitro protein synthesis, with potential for the cGMP production of disulfide‐bonded biotherapeutic proteins. Biotechnol. Bioeng. 2011; 108:1570–1578. © 2011 Wiley Periodicals, Inc.
An in silico compartmentalized metabolic model of Brassica napus enables the systemic study of regulatory aspects of plant central metabolism
Authors: Pilalis Eleftherios , Chatziioannou Aristotelis , Thomasset Brigitte , Kolisis Fragiskos
Published: February 2011

Biochemical network reconstructions represent valuable tools for the computational metabolic modeling of organisms that present a great biotechnological interest. An in silico multi‐compartmental model of the central metabolism of the plant Brassica napus (Rapeseed) was constructed, aiming to investigate the metabolic properties of the Brassicaceae family. This family comprises many plants with major importance for the energy and nutrition sector, including the model plant Arabidopsis thaliana. The model utilized as objective function to be subsequently optimized, the biomass production of rapeseed developing embryos, which are characterized by a very high, oil content, up to 60% of biomass weight. In order to study global network properties of seed metabolism, various methods were employed, like Flux Balance Analysis, Principal Component Analysis of the flux space and reaction deletion studies, which simulate the effect of gene knock‐out experiments. The model successfully simulated seed growth during the stage of oil accumulation and provided insight, regarding certain aspects of network plasticity, with the emphasis given in lipid biosynthesis regulation. Biotechnol. Bioeng. 2011; 108:1673–1682. © 2011 Wiley Periodicals, Inc.
Familiarity with and social distance from people with mental illness: Testing the mediating effects of prejudiced attitudes
Authors: Anagnostopoulos Fotios , Hantzi Alexandra
Published: February 2011

The purpose of this study was to examine prejudiced attitudes as a factor associated with social distance from people with mental illness. A total of 289 university students from Greece completed written measures assessing social distance from, prejudiced attitudes about, and familiarity with mental illness. A structural equation model with manifest variables was tested. Participants who reported to be more familiar with mental illness held stronger social care and weaker prejudiced beliefs, and consequently expressed a less strong desire for social distance. Implications of the results and suggestions for future research are outlined. Copyright © 2011 John Wiley & Sons, Ltd.
Design and Synthesis of Conformationally Constrained Cyclophilin Inhibitors Showing a Cyclosporin‐A Phenotype in C. elegans
Authors: Dunsmore Colin J. , Malone Kirk J. , Bailey Kevin R. , Wear Martin A. , Florance Hannah , Shirran Sally , Barran Perdita E. , Page Antony P. , Walkinshaw Malcolm D. , Turner Nicholas J.
Published: February 2011

Cyclophilin A (CypA) is a member of the immunophilin family of proteins and receptor for the immunosuppressant drug cyclosporin A (CsA). Here we describe the design and synthesis of a new class of small‐molecule inhibitors for CypA that are based upon a dimedone template. Electrospray mass spectrometry is utilised as an initial screen to quantify the protein affinity of the ligands. Active inhibitors and fluorescently labelled derivatives are then used as chemical probes for investigating the biological role of cyclophilins in the nematode Caenorhabditis elegans.
Targeting Bacterial Membranes: Identification of Pseudomonas aeruginosaD‐Arabinose‐5P Isomerase and NMR Characterisation of its Substrate Recognition and Binding Properties
Authors: Airoldi Cristina , Sommaruga Silvia , Merlo Silvia , Sperandeo Paola , Cipolla Laura , Polissi Alessandra , Nicotra Francesco
Published: February 2011

The identification and characterisation of Pseudomonas aeruginosa KdsD (Pa‐KdsD), a D‐arabinose‐5P isomerase involved in the biosynthesis of 3‐deoxy‐D‐manno‐oct‐2‐ulosonic acid and thus of lipopolysaccharide (LPS), are reported. We have demonstrated that KdsD is essential for P. aeruginosa survival and thus represents a key target for the development of novel antibacterial drugs. The key amino acid residues for protein activity have been identified. The structural requirements for substrate recognition and binding have been characterised for the wild‐type protein, and the effect of mutations of the key residues on catalytic activity and binding have been evaluated by saturation transfer difference (STD) NMR spectroscopy. Our data provide important structural information for the rational design of new KdsD inhibitors as potential antibacterial drugs.
Development of a highly specific ensemble of topological models for early identification of P‐glycoprotein substrates
Authors: Di Ianni Mauricio , Talevi Alan , Castro Eduardo A. , Bruno‐Blanch Luis E.
Published: February 2011

P‐glycoprotein (Pgp) is an ATP‐dependent efflux transporter protein associated with multidrug resistance in several diseases such as cancer, epilepsy and AIDS. It is preferentially expressed in organs and tissues that function as a barrier (e.g. the gut walls or the blood–brain barrier) or promote the elimination of xenobiotics from the organism (e.g. liver and kidney). Pgp limits drug bioavailability; thus, the recognition of Pgp substrates at the early stages of the drug development cycle is essential for the development of new chemotherapeutic agents to deal with multidrug resistance issues. Here we present the development of several classifier models based on topological descriptors to identify potential Pgp substrates, aimed to be applied as secondary filter in virtual screening campaigns. Receiver Operating characteristic (ROC) curves show that combination of individual models, through data fusion, in a three‐model ensemble, allows attaining higher areas under the curve and an overall better behavior in terms of sensitivity or specificity. The individual discriminant functions (dfs) presented have a performance similar to that of the previously reported models and, remarkably, our models only include low‐dimensional (up to 2D) molecular descriptors, which makes them adequate for the virtual screening of increasingly large virtual chemical repositories. Copyright © 2011 John Wiley & Sons, Ltd.
The log‐bimodal‐skew‐normal model. A geochemical application
Authors: Bolfarine Heleno , Gómez Héctor W. , Rivas Luisa I.
Published: February 2011

The main objective of this paper is to study a logarithm extension of the bimodal skew normal model introduced by Elal‐Olivero et al. 1. The model can then be seen as an alternative to the log‐normal model typically used for fitting positive data. We study some basic properties such as the distribution function and moments, and discuss maximum likelihood for parameter estimation. We report results of an application to a real data set related to nickel concentration in soil samples. Model fitting comparison with several alternative models indicates that the model proposed presents the best fit and so it can be quite useful in real applications for chemical data on substance concentration. Copyright © 2011 John Wiley & Sons, Ltd.
Synthesis of 1,2‐Amino Alcohols by Sigmatropic Rearrangements of 3‐(N‐Tosylamino)allylic Alcohol Derivatives
Authors: Barbazanges Marion , Meyer Christophe , Cossy Janine , Turner Peter
Published: February 2011

Sigmatropic rearrangements of 3‐(N‐tosylamino)allylic alcohol derivatives, a particular subclass of functionalized enamides, have been investigated. Whereas the presence of the nitrogen atom alters the stereochemical outcome of Ireland–Claisen rearrangements of glycolates derived from such substrates, [2,3]‐Wittig rearrangements of α‐allyloxy acetamides or propargylic ethers derivatives provide access to a wide variety of functionalized 1,2‐amino alcohols usually with high levels of stereocontrol, as well as to heterocyclic compounds. The stereoselectivity issues of these rearrangements (1,2‐diastereoselectivity, auxiliary‐induced diastereoselection, chirality transfer, and double stereodifferentiation) were thoroughly investigated.
ChemInform Abstract: Photoluminescence Properties and Energy‐Transfer of Thermal‐Stable Ce3+, Mn2+‐Codoped Barium Strontium Lithium Silicate Red Phosphors.
Authors: Zhang Xinguo , Gong Menglian
Published: February 2011

A series of red emitting phosphors, Ba1.8‐x‐y‐zSrx (Li2) 0.2SiO4:yCe3+,zMn2+ is prepared by solid state reaction of BaCO3, SrCO3, Li2CO3, SiO2, MnCO3, and CeO2 (90:10 N2/H2, 900 °C, 3 h).
ChemInform Abstract: The Solid Solutions Gd2Cu2In1‐xMgx — Drastic Increase of the Curie Temperature upon In/Mg Substitution.
Authors: Hermes Wilfried , Schappacher Falko M. , P�ttgen Rainer
Published: February 2011

The title solid solutions (0 ≤ x ≤ 1) are synthesized from the elements (Ta tubes, 700 mbar Ar, 1020 K, 3 h) and characterized by powder XRD and magnetic measurements.
ChemInform Abstract: YPd2Al3 — A New Superconducting Compound.
Authors: Pospisil Jiri , Kratochvilova Marie , Divis Martin , Prokleska Jan , Poltierova Vejpravova Jana , Sechovsky Vladimir
Published: February 2011

Polycrystalline samples of the new title compound are prepared by melting stoichiometric amounts of the elements in an arc‐furnace under Ar atmosphere, followed by annealing at 700 °C for 14 d.
ChemInform Abstract: Aerosol Synthesis and Rietveld Analysis of Tetragonal (β1) PdZn.
Authors: Peterson Eric J. , Halevi Barr , Kiefer Boris , Spilde Michael N. , Datye Abhaya K. , Peterson Joe , Daemen Luc , Llobet Anna , Nakotte Heinz
Published: February 2011

The title compound is synthesized with controlled composition by an aerosol method from a mixture of Pd and Zn dissolved in HNO3 followed by a reduction treatment in flowing 5% H2/N2 (500 °C, 4 h).
ChemInform Abstract: Synthesis and Hydriding Behavior of Li2MgPt.
Authors: Salvador J. R. , Herbst J. F. , Meyer M. S.
Published: February 2011

The title compound is synthesized by milling of a mixture of Li, Mg, and Pt in the atomic ratio of 2:1.5:1 (high energy mill, 5 h, argon atmosphere).
ChemInform Abstract: Copper‐Catalyzed Direct Carboxylation of C—H Bonds with Carbon Dioxide.
Authors: Zhang Liang , Cheng Jianhua , Ohishi Takeshi , Hou Zhaomin
Published: February 2011

The direct carboxylation of benzoxazoles proceeds via isolable benzoxazolyl copper compounds and carboxylate complexes to afford the corresponding esters in good yields.
ChemInform Abstract: PEG‐Mediated Facile Protocol for N‐Boc Protection of Amines.
Authors: Siddaiah V. , Basha G. M. , Rao G. Padma , Prasad U. Viplava , Rao R. Suryachendra
Published: February 2011

A simple, efficient, eco‐friendly, and highly chemoselective protocol for the title protection is developed.
ChemInform Abstract: tmp4Zr: An Atom‐Economical Base for the Metalation of Functionalized Arenes and Heteroarenes.
Authors: Jeganmohan Masilamani , Knochel Paul
Published: February 2011

A directed metalation of a broad spectrum of functionalized arenes and hetarenes is developed using the new base.
ChemInform Abstract: Direct Addition of Functionalized Organozinc Reagents to Carbon Dioxide, Ketones, and Aldehydes in the Presence of MgCl2.
Authors: Bernhardt Sebastian , Metzger Albrecht , Knochel Paul
Published: February 2011

Efficient addition of functionalized organozinc reagents to various carbonyl derivatives and CO2 is achieved in the presence of MgCl2.
ChemInform Abstract: Shape‐Persistent Arylenevinylene Macrocycles (AVMs) Prepared via Acyclic Diene Metathesis Macrocyclization (ADMAC).
Authors: Jin Yinghua , Zhang Aibo , Huang Yongshun , Zhang Wei
Published: February 2011

A one‐step synthesis, UV‐VIS absorption and fluorescence properties, and aggregation behavior of two arylenevinylene macrocycles are reported.
ChemInform Abstract: Isomerization of Allyl Ethers Initiated by Lithium Diisopropylamide.
Authors: Su Chicheung , Williard Paul G.
Published: February 2011

A wide range of allylic ethers is converted to the corresponding (Z)‐propenyl ethers on treatment with LDA.
ChemInform Abstract: Efficient Synthesis of Highly Functionalized Vinylogous Thiol Esters.
Authors: Liu Jinglin , Xu Xianxiu , Li dongwei , Zhang Lei , Zhang Kun , Liu Qun
Published: February 2011

The title compounds can be easily prepared by thermal reaction of thioacetals with diester (II).
ChemInform Abstract: Rauhut—Currier Type Homo‐ and Heterocouplings Involving Nitroalkenes and Nitrodienes.
Authors: Shanbhag Pramod , Nareddy Pradeep R. , Dadwal Mamta , Mobin Shaikh M. , Namboothiri Irishi N. N.
Published: February 2011

A variety of aromatic and aliphatic nitroalkenes or nitrodienes undergoes heterocoupling reaction with methyl vinyl ketone (II) or acrylate (IV) in the presence of LiCl and imidazole.
ChemInform Abstract: Regiospecific Azidoiodination of Alkenes with Sodium Periodate, Potassium Iodide, and Sodium Azide: A High‐Yield Synthesis of β‐Iodoazides.
Authors: Chouthaiwale Pandurang V. , Karabal Pratibha U. , Suryavanshi Gurunath , Sudalai Arumugam
Published: February 2011

The simple and mild synthesis furnishes exclusively the anti‐Markovnikov adducts in excellent yields.
ChemInform Abstract: Aminoarenethiolato—Copper(I) as (Pre‐)Catalyst for the Synthesis of Diaryl Ethers from Aryl Bromides and Sequential C—O/C—S and C—N/C—S Cross Coupling Reactions.
Authors: Sperotto Elena , van Klink Gerard P. M. , de Vries Johannes G. , van Koten Gerard
Published: February 2011

The arylation of phenols with aryl bromides is smoothly catalyzed by an aminoarenethiolato—Cu(I) complex (2.5mol%) to give phenol ethers (III) and (V) in moderate to good yields.
ChemInform Abstract: Cerium(III)‐Catalyzed Synthesis of Schiff Bases: A Green Approach.
Authors: Ravishankar Lakshmy , Patwe Siddhartha A. , Gosarani Nehal , Roy Aparajita
Published: February 2011

The presented reaction is also tested without the use of the catalyst but this results in lower yields.
ChemInform Abstract: Sequential Double α‐Arylation of N‐Allylureas by Asymmetric Deprotonation and N→C Aryl Migration.
Authors: Tetlow Daniel J. , Hennecke Ulrich , Raftery James , Waring Michael J. , Clarke David S. , Clayden Jonathan
Published: February 2011

The aryl transfer from nitrogen to the allylic α‐carbon of the starting N‐allyl‐N′‐aryl ureas proceeds upon treatment with the lithium base (LDA) and DMPU [cf.
ChemInform Abstract: Efficient Synthesis and Ring‐Opening Reactions of Monofluorinated Epoxides Derived from α‐Fluorosulfoximines.
Authors: Zhang Wei , Hu Jinbo
Published: February 2011

Monofluorinated epoxides are successfully prepared through the O‐cyclization reaction between α‐fluorosulfoximines (I), (XII), and (XIV) and ketones whereas, analogous reactions of (I) with aldehydes give complex mixtures.
ChemInform Abstract: A Novel Approach for the Synthesis of Furopyrimidine and Oxobenzofuran Derivatives.
Authors: Bayat Mohammad , Shiraz Nader Zabarjad , Hosseini Seyyed Hajar
Published: February 2011

A simple one‐pot procedure is developed for the three‐component reaction.