bluuebunny/crossref_metadata_2025 huggingface dataset:
A Paradigm for the Radical‐Mediated Photochemical Synthesis of Metal Nanostructures
Authors: Scaiano Juan C. , Stamplecoskie Kevin G. , McGilvray Katherine L. , Pacioni Natalia L.
Published: March 2012

Photochemical methods for free radical generation can provide a powerful tool to design new strategies for the synthesis of metal nanostructures. In particular, the Norrish type I cleavage of substituted benzoins can be employed as a source of strongly reducing radicals, described here as “caged electrons.” A key to an efficient nanostructure synthesis relies on the prevention of excited state quenching by the transition metal ions used as metal precursors; the paradigm presented here emphasizes the spatial‐temporal strategies that can ensure the survival of excited states so that they can perform as efficient sources of caged electrons.
Silanes as Reducing Reagents in Radical Chemistry
Authors: Chatgilialoglu Chryssostomos , Timokhin Vitaliy I.
Published: March 2012

This article focuses on the recent advances in organic synthesis based on the role of silyl radicals. The numerous examples of the successful use of organosilanes, and in particular tris(trimethylsilyl)silane, as radical‐based reducing agents show the flexibility and applicability of these compounds in two classes of transformations: radical reductions and consecutive radical reactions. The use of organosilanes allows reactions to be carried out under mild conditions, in different solvents including water, with excellent yields of products and remarkable chemo‐, regio‐, and stereoselectivity. The future perspectives of silyl radicals in a broad range of new synthetic applications are also given.
Biological Chemistry of Reactive Oxygen Species
Authors: Winterbourn Christine C.
Published: March 2012

Living organisms are continually exposed to free radicals and other reactive oxygen species as a result of metabolizing oxygen and other redox‐active compounds. Excessive production can result in biological damage, whereas in other situation, specific oxidants are generated as a host defense mechanism or as a cell signal that activates gene expression and metabolic responses. This article provides an overview of the specific reactive oxygen species that are generated biologically, how and where they arise, and their chemical reactivity with biological molecules.
Kinetics of Polymerizations
Authors: Buback Michael , Russell Gregory T.
Published: March 2012

First of all, the machinery for treating radical polymerization (RP) kinetics is presented. On the one hand, this involves kinetic descriptions that may be implemented without undue difficulty and that account for subtle but pivotal phenomena such as chain‐length‐dependent termination and penultimate‐unit effects in copolymerization. At the same time, this machinery also includes reliable, probing experimental methods for measuring rate coefficients. It is then shown how these tools have been used to develop mechanistic understanding of the fundamental RP reactions, which are initiation, propagation, termination, and chain transfer. In the case of propagation, there is a particular emphasis on entropic effects arising from hindered rotations, while with termination the composite model for chain‐length dependence is stressed, as is variation of overall termination rate coefficient with conversion. Finally, it is shown that chain transfer to polymer and β‐scission are recurring and important motifs in many RP systems. All in all, a pleasing picture of a scientifically maturing field is revealed as taking shape.
Synthetic Radical Photochemistry
Authors: Riguet Emmanuel , Hoffmann Norbert
Published: March 2012

Photochemically induced radical reactions as key steps in organic synthesis are mainly reported. In this context, photochemical electron transfer plays an important role. Currently, many ruthenium‐complex photocatalyzed reactions are investigated. Such transformations have been combined with organocatalysis. Free radical intermediates are also generated in photochemical reactions of carbonyl compounds such as in the Norrish and related reactions. These transformations have also been applied in multistep synthesis. Intramolecular remote functionalization has been carried out most frequently with steroid derivatives. Application to the preparation of alkaloids has also been reported. Compounds processing sulfur‐containing functional groups play a central role in free radical chemistry. Corresponding reactions have also been induced under photochemical conditions. Tin compounds are frequently used as substrate or to induce radical chain reactions. The homolytic fragmentation of these compounds has also been carried out by UV irradiation. Particularly, hexaalkylditin derivatives are activated in this way.
Reliability of the novel 7‐joint ultrasound score: Results from an inter‐ and intraobserver study performed by rheumatologists
Authors: Ohrndorf S. , Fischer I. U. , Kellner H. , Strunk J. , Hartung W. , Reiche B. , Burmester G. R. , Walther M. , Schmidt W. A. , Backhaus M.
Published: March 2012

Objective

To assess the inter‐ and intraobserver reliability of 26 rheumatologists when performing the 7‐joint ultrasound score (US7).

Methods

Six patients with rheumatoid arthritis were examined by 26 sonographers in 12 rater groups who performed the US7 score. The US7 score includes the clinically dominant wrist, the second and third metacarpophalangeal (MCP) and proximal interphalangeal joints, and the second and fifth metatarsophalangeal (MTP) joints, which were evaluated for synovitis, tenosynovitis/paratenonitis, and erosions from the dorsal side and palmar/plantar aspects by gray‐scale and power Doppler (PD) ultrasound. Additional lateral scans were performed at the MCP2 and MTP5 joints. All of the groups repeated the examination in 4 patients in order to calculate the intraobserver reliability. The results of one group that included 2 expert sonographers were considered as the reference standard. Kappa values, median agreement rates (interobserver), and P values (intraobserver evaluation) were calculated.

Results

The median overall kappa value for detecting synovitis was 0.51, for tenosynovitis/paratenonitis was 0.57, and for erosions was 0.45. In detail, the best interobserver results were found for the detection of erosions in the MTP2 joint from the plantar aspect (κ = 1; median agreement rate 89.4%) and for PD signal detection in the palmar wrist region (κ = 0.79; median agreement rate 78.8%). Good agreement was found for detecting erosions in the MCP2 joint from the radial side (κ = 0.67; median agreement rate 77.3%).

Conclusion

The inter‐ and intraobserver reliability of the US7 score shows moderate to substantial kappa values and good agreements. Therefore, this ultrasound score has the potential to be an important imaging tool, including multicenter analysis to assess structural changes.
Enhancing life after cancer in diverse communities
Authors: Kaur Judith S. , Coe Kathryn , Rowland Julia , Braun Kathryn L. , Conde Francisco A. , Burhansstipanov Linda , Heiney Sue , Kagawa‐Singer Marjorie , Lu Qian , Witte Catherine
Published: March 2012

BACKGROUND:

Although large numbers of cancer survivors exist in every community, including minority communities, there is a significant gap in knowledge about best practices for these patients.

METHODS:

The Community Networks Program, funded by the National Cancer Institute Center to Reduce Cancer Health Disparities, has developed and tested unique services for these communities. These programs have used community‐based participatory research techniques under a framework of diffusion of innovation and communications theory.

RESULTS:

This article describes some specifically tailored interventions that may be useful to a wide range of providers working with the underserved.

CONCLUSIONS:

Enhancing life after cancer can be achieved in underserved communities by supplementing local resources. Cancer 2012. © 2012 American Cancer Society.
Trends in colorectal cancer screening with home‐based fecal occult blood tests in adults ages 50 to 64 years, 2000‐2008
Authors: Bandi Priti , Cokkinides Vilma , Smith Robert A. , Jemal Ahmedin
Published: March 2012

BACKGROUND:

National surveys have reported declines in rates of home‐based fecal occult blood test (FOBT) screening for colorectal cancer (CRC) in the last decade. However, socioeconomic status (SES) and racial/ethnic differences in FOBT trends and their changes relative to endoscopic CRC screening have not been evaluated.

METHODS:

Data on adults ages 50 to 64 years from the 2000, 2005, and 2008 National Health Interview Surveys were used. Weighted analyses and multivariate logistic regression were used to study trends in the use of FOBT and endoscopic CRC screening during this period.

RESULTS:

Between 2000 and 2008, significant declines in FOBT prevalence occurred in higher SES groups, but not in lower SES groups (uninsured and publicly insured, those without a usual source of care, lower educated, lower income, and immigrants to the United States) or Hispanics. Endoscopic CRC screening during the period studied consistently increased in all higher SES subgroups. In contrast, few lower SES subgroups (publicly insured, lower educated, near poor individuals, long‐term immigrants) and Hispanics experienced increases in CRC endoscopic screening, and these increases were smaller than those observed in higher SES subgroups.

CONCLUSIONS:

Socially and economically disadvantaged groups experienced little or no change in FOBT prevalence, and few of these groups experienced contemporaneous increases in CRC endoscopic screening. These trends suggest the continued availability and acceptance of FOBT in these groups. If national CRC screening goals are to be achieved in populations with lower access to colonoscopy, then annual high‐sensitivity FOBT should be promoted as an immediately accessible and viable alternative. Cancer 2012. © 2012 American Cancer Society.
A novel Cre/loxP system for mosaic gene expression in the Drosophila embryo
Authors: Nakazawa Naotaka , Taniguchi Kiichiro , Okumura Takashi , Maeda Reo , Matsuno Kenji
Published: March 2012

Background: Mosaic analysis is used to assess gene function and cell autonomy in a subset of cells in an organism, and has been extensively applied in Drosophila studies. However, it is difficult to generate mosaic cells in Drosophila embryonic tissues using existing methods. Therefore, we developed a new method for generating genetic mosaic embryos using a modified Cre/loxP system. In this report, we also characterized the capabilities and limitations of this novel method. Results: We first constructed a novel cassette combining loxP with the Actin 5C enhancer and Gal4 cDNA, and generated a transgenic fly carrying this construct (Aloxg‐Gal4). In Aloxg‐Gal4, the activation of Gal4 expression is suppressed by the gypsy insulator. Once the gypsy insulator is removed, however, Gal4 is expressed when site‐specific recombination between loxP sites is induced by Cre recombinase. This system allowed the mosaic expression of Gal4 in Drosophila embryonic tissues (epidermis, amnioserosa, tracheal system, malpighian tubules, foregut, hindgut, midgut, and neuron), leading to the Gal4‐dependent activation of arbitrary genes under the control of the upstream activation sequence (UAS). Conclusions: This practical method can be used to generate mosaic cells in Drosophila embryonic tissues and can be applied to any gene without specialized equipment. Developmental Dynamics 241:965–974, 2012. © 2012 Wiley Periodicals, Inc.
An efficient learning method for layered neural networks based on selection of training data and input characteristics of an output layer unit
Authors: Taguchi Isao , Sugai Yasuo
Published: March 2012

This paper proposes an efficient learning method for a layered neural network based on the selection of training data and the input characteristics of an output layer unit. Compared to recent neural networks, pulse neural networks, and quantum neuro computation, the multilayer neural network is widely used due to its simple structure. When learning objects are complicated, problems such as unsuccessful learning or a significant time required in learning remain unsolved. The aims of this paper are to suggest solutions for these problems and to reduce the total learning time. The total learning time means the total computational time required to learn certain objects, including adjusting parameter values and restarting learning from the beginning. Focusing on the input data during the learning stage, we undertook an experiment to identify the data that create large errors and interfere with the learning process. Our method divides the learning process into several stages. In general, the input characteristics to an output layer unit show oscillation during the learning process for complicated problems. Focusing on the oscillatory characteristics, it is determined whether the learning will move on to the next stage or the learning will restart from the beginning. Computational experiments suggest that the proposed method has the capability for higher learning performance and needs less learning time compared with the conventional method. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(4): 57–67, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10365
Secondary Face‐to‐Face 2–2′ β‐Cyclodextrin Dimers Linked with Fluorescent Rigid Spacer Arms: A Cyclodextrin‐Based Ratiometric Sensor for Bile Salts
Authors: Martos‐Maldonado Manuel C. , Quesada‐Soriano Indalecio , Casas‐Solvas Juan M. , García‐Fuentes Luis , Vargas‐Berenguel Antonio
Published: March 2012

The synthesis of a series of β‐cyclodextrin (CD) dimers in which the two macrocycle units are linked by rigid‐rod phenylene‐ethynylene tethers of different length and shape through the cyclodextrin secondary sides is reported. The synthesis involves Sonogashira coupling reactions for construction of the tethers and final grafting of the CD units by click chemistry. The self‐aggregation of the synthesized CD dimers in aqueous medium was investigated by fluorescence spectroscopy, isothermal titration calorimetry and dynamic light scattering. Rigid‐rod‐tethered cyclodextrin dimers formed polydisperse nanoparticles of 240 to 480 nm in water solution depending on the tether shape, and exhibited fluorescence. The binding and fluorescence sensing abilities of the CD dimers toward sodium cholate and deoxycholate were studied. As a result, the newly synthesized rigid‐rod‐tethered cyclodextrin dimers proved to be very sensitive fluorescent chemosensors. A new cyclodextrin‐based ratiometric fluorescence probe has thus been developed for the detection of bile salts such as sodium cholate and deoxycholate.
Trichoderones A and B: Two Pentacyclic Cytochalasans from the Plant Endophytic Fungus Trichoderma gamsii
Authors: Ding Gang , Wang Hailou , Li Li , Chen Amanda Juan , Chen Lin , Chen Hong , Zhang Hongwu , Liu Xinzhong , Zou Zhongmei
Published: March 2012

Two new cytochalasans, trichoderones A (1) and B (2), and three known analogues, aspochalasins D (3), J (4), and I (5), were isolated from the endophytic fungus Trichoderma gamsii. Their structures were determined by analysis of their spectroscopic data. The absolute configurations of 1 and 2 were established by quantum chemical electronic circular dichroism calculations. Compounds 3 and 4 displayed cytotoxic activity against the HeLa cell line. Trichoderone A (1) possesses an unprecedented 7/6/6/5/5 pentacyclic system, whereas trichoderone B (2) contains the rare 6/5/6/6/5 pentacyclic skeleton with a 12‐oxatricyclo [6.3.1.02,7] moiety.
High performance chromium (VI) removal from water by polyacrylonitrile‐co‐poly (2‐ethyl hexylacrylate) and polyaniline nanoporous membranes
Authors: Bozkir Selcuk , Sankir Mehmet , Semiz Levent , Sankir Nurdan D. , Usanmaz Ali
Published: March 2012

This article reports the chromium (VI) removal from water by preparing polyacrylonitrile‐co‐poly (2‐ethyl hexylacrylate) (PAN(92)‐co‐P2EHA(8)) and polyaniline (PANI) nanoporous membranes at various PANI loadings. It was observed that chromium (VI) rejections of nanoporous membranes are highly concentration and pH dependent. Almost complete chromium removal (99.9%) with higher flux values (120–177 L m−2 h−1) was observed for nanoporous membranes. Moreover, nanoporous membranes were also demonstrated as fouling resistant. Total flux loss was low and a part was attributed to reversible flux loss, which cannot cause any permanent hysteresis and easily overcome with simple washing. Scanning electron microscopy (SEM) studies were performed for identifying cross sectional morphology. It was pointed out that pore size should be small enough for filtration and optimized for higher flux but pores should be functionalized for rejection. Chemical structure, swelling ratios, sheet resistivity, and fracture morphologies of nanoporous membranes were reported. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers
Supercritical CO2 as an exfoliating aid for nanocomposite preparation: Comparison of different processing methodologies
Authors: Thompson M.R. , Zhuang Z. , Liu J. , Rodgers W.R.
Published: March 2012

This article examines several new methods for compounding nanocomposite materials by twin screw extrusion that use supercritical CO2 as a processing aid to produce more highly exfoliated polyolefin‐layered silicate nanocomposites than conventional melt intercalation. These methods varied the manner in which the plasticizing behavior of CO2 influences the surfactant of an organoclay, the compatibilizer, and the matrix during preparation of a polyolefin nanocomposite. The results have shown that targeting CO2 to the organoclay‐compatibilizer interface can improve the extent of intercalation. However, reduced performance was observed when CO2 was introduced predominantly to the matrix or neat organoclay. In general, the different techniques of addition for CO2 did bring about greater structural changes to the organoclay, but the stiffness of the resulting materials was lower than simply following a conventional melt intercalation approach. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers
Mind matters in cancer survival
Authors: Spiegel David
Published: March 2012

Objective

The very name “psycho‐oncology” implies interaction between brain and body. One of the most intriguing scientific questions for the field is whether or not living better may also mean living longer.

Methods

Randomized intervention trials examining this question will be reviewed.

Results

The majority show a survival advantage for patients randomized to psychologically effective interventions for individuals with a variety of cancers, including breast, melanoma, gastrointestinal, lymphoma, and lung cancers. Importantly, for breast and other cancers, when aggressive anti‐tumor treatments are less effective, supportive approaches appear to become more useful. This is highlighted by a recent randomized clinical trial of palliative care for non‐small cell lung cancer patients.There is growing evidence that disruption of circadian rhythms, including rest‐activity patterns and hypothalamic–pituitary–adrenal (HPA) axis function, affects cancer risk and progression. Women with metastatic breast cancer have flatter diurnal cortisol patterns than normal, and the degree of loss of daily variation in cortisol predicts earlier mortality. Mechanisms by which abnormal cortisol patterns affect metabolism, gene expression, and immune function are reviewed. The HPA hyperactivity associated with depression can produce elevated levels of cytokines that affect the brain. Tumor cells can, in turn, co‐opt certain mediators of inflammation such as NFkB, interleukin‐6, and angiogenic factors to promote metastasis. Also, exposure to elevated levels of norepinephrine triggers release of vascular endothelial growth factor, which facilitates tumor growth.

Conclusions

Therefore, the stress of advancing cancer and management of it is associated with endocrine, immune, and autonomic dysfunction that has consequences for host resistance to cancer progression.

Copyright © 2012 John Wiley & Sons, Ltd.
Investigation of Size‐Dependent Plasmonic and Catalytic Properties of Metallic Nanocrystals Enabled by Size Control with HCl Oxidative Etching
Authors: Li Bo , Long Ran , Zhong Xiaolan , Bai Yu , Zhu Zijie , Zhang Xing , Zhi Min , He Jiawei , Wang Chengming , Li Zhi‐Yuan , Xiong Yujie
Published: March 2012

Particle size is one important parameter of nanocrystals that need to be tightly controlled, owing to its versatility for tailoring the properties and functions of nanocrystals towards various applications. In this article, oxidative etching by hydrogen chloride is employed as a tool to control the size of metallic nanocrystals. As a result of the size control, investigations into the size‐dependent plasmonic and catalytic properties of metallic nanocrystals can be investigated. Given that the shape can be kept consistent when tuning the particle size in this system, it enables the systematic investigation of size‐dependent properties free of the influence of other factors such as shape effect.
Microfluorescence Analysis of Nanostructuring Inhomogeneity in Optical Fibers with Embedded Gallium Oxide Nanocrystals
Authors: Mashinsky Valery M. , Karatun Nikita M. , Bogatyrev Vladimir A. , Sigaev Vladimir N. , Golubev Nikita V. , Ignat'eva Elena S. , Lorenzi Roberto , Mozzati Maria Cristina , Paleari Alberto , Dianov Evgeny M.
Published: March 2012

A spectroscopic protocol is proposed to implement confocal microfluorescence imaging to the analysis of microinhomogeneity in the nanocrystallization of the core of fibers belonging to a new kind of broadband fiber amplifier based on glass with embedded nanocrystals. Nanocrystallization, crucial for achieving an adequate light emission efficiency of transition metal ions in these materials, has to be as homogeneous as possible in the fiber to assure optical amplification. This requirement calls for a sensitive method for monitoring nanostructuring in oxide glasses. Here we show that mapping microfluorescence excited at 633 nm by a He-Ne laser may give a useful tool in this regard, thanks to quasi-resonant excitation of coordination defects typical of germanosilicate materials, such as nonbridging oxygens and charged Ge-O-Ge sites, whose fluorescence are shown to undergo spectral modifications when nanocrystals form into the glass. The method has been positively checked on prototypes of optical fibers—preventively characterized by means of scanning electron microscopy and energy dispersive spectroscopy—fabricated from preforms of Ni-doped Li2O-Na2O-Sb2O3-Ga2O3-GeO2-SiO2 glass in silica cladding and subjected to heat treatment to activate gallium oxide nanocrystal growth. The method indeed enables not only the mapping of the crystallization degree but also the identification of drawing-induced defects in the fiber cladding.
Fabrication of ultrathin L1-FePt based exchange coupled composite media
Authors: Zhao Haibao , Wang Hao , Wang Jian-Ping
Published: March 2012

Ultrathin exchange coupled composite (ECC) FePt granular recording media with different soft layer anisotropy were fabricated by controlling the soft layer deposition temperature. As the soft layer (FePt-SiO2) deposition temperature (TSoft) increased, the overall FePt (001) texture of ECC FePt thin films was improved, while the saturation magnetization (Ms) and the thermal stability factor were also increased. The effect of soft layer anisotropy field on the coercivity (Hc) and the remanent coercivity (Hcr) of ECC FePt thin films showed a “V” shape relationship, with the minimums at TSoft of 200 °C. These results are consistent with the theoretic predication based on domain wall assisted magnetization reversal mechanism. The ECC FePt thin film with TSoft of 200 °C may have a gain factor larger than 2.
Surface Modified Gold Nanorods in Two Photon Luminescence Imaging
Authors: Zhang J. B. , Balla N. K. , Gao C. , Sheppard C. J. R. , Yung L. Y. L. , Rehman S. , Teo J. Y. , Kulkarni S. R. , Fu Y. H. , Yin Sze Jia
Published: March 2012

Gold nanorods (AuNRs) possess unique optical properties which make them good contrast agents for optical microscopy. Their longitudinal plasmon resonance peak can be easily tuned from red to near infrared wavelength by increasing their aspect ratio to match the wavelengths of different imaging modalities. AuNRs are also stronger scatterers of light as compared with gold nanospheres. Nevertheless what sets them apart from other gold nanoparticles is their strong multiphoton luminescence. AuNRs are therefore being increasingly used as contrast agents for multiphoton microscopy of biological samples. In this study, control of the longitudinal resonance peak of gold nanorods is investigated with comparison of two chemical synthesis approaches. Both based on a seed-mediated method, one approach is to tune the aspect ratio through manipulation of the ratio of gold seeds to gold salt and the other is through variation of the volume of hydrochloric acid. The synthesized gold nanorods were made biocompatible by replacing the cytotoxic cetyltrimethylammonium bromide (CTAB) molecules with either silica (SiO2) or polyethylene glycol (PEG). Multiphoton imaging of gold nanorods taken up by cells was demonstrated and the effect of PEG chain length on passive uptake of gold nanorods by cells is discussed.
Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells
Authors: Kubicek Stefan , Gilbert Joshua C. , Fomina-Yadlin Dina , Gitlin Alexander D. , Yuan Yuan , Wagner Florence F. , Holson Edward B. , Luo Tuoping , Lewis Timothy A. , Taylor Bradley , Gupta Supriya , Shamji Alykhan F. , Wagner Bridget K. , Clemons Paul A. , Schreiber Stuart L.
Published: March 2012

Under the instruction of cell-fate–determining, DNA-binding transcription factors, chromatin-modifying enzymes mediate and maintain cell states throughout development in multicellular organisms. Currently, small molecules modulating the activity of several classes of chromatin-modifying enzymes are available, including clinically approved histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors. We describe the genome-wide expression changes induced by 29 compounds targeting HDACs, DNMTs, histone lysine methyltransferases (HKMTs), and protein arginine methyltransferases (PRMTs) in pancreatic α- and β-cell lines. HDAC inhibitors regulate several hundred transcripts irrespective of the cell type, with distinct clusters of dissimilar activity for hydroxamic acids and orthoamino anilides. In contrast, compounds targeting histone methyltransferases modulate the expression of restricted gene sets in distinct cell types. For example, we find that G9a/GLP methyltransferase inhibitors selectively up-regulate the cholesterol biosynthetic pathway in pancreatic but not liver cells. These data suggest that, despite their conservation across the entire genome and in different cell types, chromatin pathways can be targeted to modulate the expression of selected transcripts.
What is an ‘elasmobranch’? The impact of palaeontology in understanding elasmobranch phylogeny and evolution
Authors: Maisey J. G.
Published: March 2012

The Subclass Elasmobranchii is widely considered nowadays to be the sister group of the Subclass Holocephali, although chimaeroid fishes were originally classified as elasmobranchs along with modern sharks and rays. While this modern systematic treatment provides an accurate reflection of the phylogenetic relationships among extant taxa, the classification of many extinct non‐holocephalan shark‐like chondrichthyans as elasmobranchs is challenged. A revised, apomorphy‐based definition of elasmobranchs is presented in which they are considered the equivalent of neoselachians,i.e.a monophyletic group of modern sharks and rays which not only excludes all stem and crown holocephalans, but also many Palaeozoic shark‐like chondrichthyans and even close extinct relatives of neoselachians such as hybodonts. The fossil record of elasmobranchs (i.e.neoselachians) is reviewed, focusing not only on their earliest records but also on their subsequent distribution patterns through time. The value and limitations of the fossil record in answering questions about elasmobranch phylogeny are discussed. Extinction is seen as a major factor in shaping early elasmobranch history, especially during the Triassic. Extinctions may also have helped shape modern lamniform diversity, despite uncertainties surrounding the phylogenetic affinities of supposedly extinct clades such as cretoxyrhinids, anacoracids and odontids. Apart from these examples, and the supposed Cretaceous extinction of ‘sclerorhynchids’, elasmobranch evolution since the Jurassic has mostly involved increased diversification (especially during the Cretaceous). The biogeographical distribution of early elasmobranchs may be obscured by sampling bias, but the earliest records of numerous groups are located within the Tethyan realm. The break‐up of Gondwana, and particularly the opening of the South Atlantic Ocean (together with the development of epicontinental seaways across Brazil and Africa during the Cretaceous), provided repeated opportunities for dispersal from both eastern (European) and western (Caribbean) Tethys into newly formed ocean basins.
Human recombinant granulocyte‐macrophage colony stimulating factor (hrGM‐CSF) improves double hemibody irradiation (DHBI) tolerance in patients with stage III multiple myeloma: A pilot study
Authors: Troussard X. , Macro M. , Vie B. , Batho A. , Peny A. M. , Reman O. , Tabah I. , Leporrier M.
Published: March 2012

Summary. Double hemibody irradiation (DHBI) is an alternative treatment of stage III multiple myeloma (MM) in patients aged over 55 years. Toxic side‐effects such as myelosuppression are a severe limiting factor to its use. We performed DHBI associated with human recombinant granulocyte‐macrophage colony stimulating factor (hrGM‐CSF) as support therapy in 10 patients with stage III MM to improve the tolerance to this treatment.

Ten patients received subcutaneously 5 μg/kg/d of hrGM‐CSF during 2 weeks after each course of hemibody irradiation. All these patients had stage III MM: eight previously received chemotherapy, six of them were regarded as patients with refractory MM and two with relapse. Two patients received DHBI as first‐line treatment.

hrGM‐CSF increased safety and tolerance of DHBI. GM‐CSF support reduced the mean time between upper body irradiation (UBI) and lower body irradiation (LBI): 41v108d in a cohort of 32 patients previously treated without growth factor support. Overall there was no lethal infection with hrGM‐CSF or granulocytopenia (5.0 × 109/1 v 0.4 × 109/l at day 15 in patients without growth factor). hrGM‐CSF also reduced stomatitis grading and thrombocytopenia (90 × 109/l v 45 × 109/l at day 15). Furthermore, hrGM‐CSF increased blood colony forming unit‐granulocyte macrophage (CFU‐GM) and was well tolerated in all but one patient.

hrGM‐CSF reduces toxic side‐effects of DHBI, thus providing an effective treatment in patients with advanced and resistant MM.
The fate of assimilated nitrogen in streams: an in situ benthic chamber study
Authors: O’BRIEN JONATHAN M. , HAMILTON STEPHEN K. , PODZIKOWSKI LAURA , OSTROM NATHANIEL
Published: March 2012

1. Nitrogen (N) processing in streams has been investigated using whole‐stream 15N addition experiments that, in general, have found that a large proportion of added nitrate removed from the water column appears to be assimilated by the stream benthos. The long‐term fate of this retained N is unknown, and of particular interest is the possibility that it becomes denitrified through coupled mineralisation–nitrification–denitrification processes (indirect denitrification).

2. We used in situ chambers to produce highly 15N‐enriched benthic biofilms and removed the chambers to allow biofilms to interact with ambient stream conditions. Nitrogen assimilation and direct denitrification were estimated from the first chamber deployment. Chambers were periodically reinstalled over 4 weeks to measure tracer 15N in ammonium (), nitrate () and dinitrogen (N2), from which we estimated subsequent rates of biotic N transformations, including N mineralisation (ammonification), nitrification and indirect denitrification. We also estimated rates of depuration of 15N tracer from benthic biomass compartments.

3. Nitrate uptake was roughly equivalent in the sand and cobble habitats that dominated the stream. Direct denitrification (denitrification of from the water column) was an order of magnitude higher in cobble habitats than in sand habitats, accounting for c. 26 and 2% of total nitrate uptake in cobble and sand, respectively.

4. Mean residence times of actively cycling organic N in stream benthos (algae and microbes) were 16 days in cobble habitats and 9 days in sand habitats. The difference between habitat types was driven by the influence of N residence time in epilithic biofilms (18 days) on cobbles.

5. Release of enriched 15 was the primary flux of remineralised N, while release of enriched 15 was an order of magnitude less. We detected slight 15N enrichment in dissolved nitrogen gas (N2) in post‐enrichment sampling, indicating that indirect denitrification was taking place. However, indirect denitrification accounted for <0.1% of the assimilated N.

6. These experiments agree with results of whole‐stream 15N additions, in that most added N was assimilated rather than directly denitrified. Assimilation was primarily a short‐term N retention mechanism in this stream, and indirect denitrification of assimilated N accounted for only a minor proportion of the observed 15N loss over time.

7. Remaining possible fates include export of N as particulate organic matter, which may lead to additional storage of assimilated N in downstream habitats, and consumption by grazers.
Two Types of Burst Firing in Gonadotrophin‐Releasing Hormone Neurones
Authors: Chu Z. , Tomaiuolo M. , Bertram R. , Moenter S. M.
Published: March 2012

Gonadotrophin‐releasing hormone (GnRH) neurones fire spontaneous bursts of action potentials, although little is understood about the underlying mechanisms. In the present study, we report evidence for two types of bursting/oscillation driven by different mechanisms. Properties of these different types are clarified using mathematical modelling and a recently developed active‐phase/silent‐phase correlation technique. The first type of GnRH neurone (1–2%) exhibits slow (∼0.05 Hz) spontaneous oscillations in membrane potential. Action potential bursts are often observed during oscillation depolarisation, although some oscillations were entirely subthreshold. Oscillations persist after blockade of fast sodium channels with tetrodotoxin (TTX) and blocking receptors for ionotropic fast synaptic transmission, indicating that they are intrinsically generated. In the second type of GnRH neurone, bursts were irregular and TTX caused a stable membrane potential. The two types of bursting cells exhibited distinct active‐phase/silent‐phase correlation patterns, which is suggestive of distinct mechanisms underlying the rhythms. Further studies of type 1 oscillating cells revealed that the oscillation period was not affected by current or voltage steps, although amplitude was sometimes damped. Oestradiol, an important feedback regulator of GnRH neuronal activity, acutely and markedly altered oscillations, specifically depolarising the oscillation nadir and initiating or increasing firing. Blocking calcium‐activated potassium channels, which are rapidly reduced by oestradiol, had a similar effect on oscillations. Kisspeptin, a potent activator of GnRH neurones, translated the oscillation to more depolarised potentials, without altering period or amplitude. These data show that there are at least two distinct types of GnRH neurone bursting patterns with different underlying mechanisms.
Anatomy and Anaesthesia of the Equine External Ear Canal
Authors: Sommerauer S. , Muelling C. K. W. , Seeger J. , Schusser G. F.
Published: March 2012

Anaesthesia of the external ear canal (external acoustic meatus) is usually performed by blocking both the great and internal auricular nerves by regional infiltration. However, exact landmarks for blocking the internal auricular nerve to accomplish effective anaesthesia have not been described yet. In this study, detailed anatomical dissection of the equine external ear canal and its nerve supply was carried out on fifteen cadaver heads. Tissue samples of the dissected nerves were taken from two cadaver heads processed and were evaluated microscopically. Prior to the dissection, the region of interest was evaluated ultrasonographically, and injection of a local anaesthetic was simulated with an injection of methylene blue on ten cadaver heads. The tympanic membranes of three cadaver heads were obtained by microdissection and processed for microscopic evaluation. The entrance point of the internal auricular nerve, which is a branch of the facial nerve, into the ear canal is formed by the styloid process of the auricular cartilage. Using ultrasound, the styloid process presented as a thin hyperechoic line 2.17–2.97 cm deep, based on the skin surface. Landmarks for performing a complete and reliable anaesthesia of the external ear canal were established, and the simulated anaesthesia with methylene blue injection was evaluated as successful in all ten cases. Additionally, the histological composition of the equine tympanic membrane is described and illustrated.
Mucinous cystadenocarcinoma of the breast with a basal‐like immunophenotype
Authors: Deng Yunte , Xue Debin , Wang Xiaoyan , Xu Sanpeng , Ao Qilin , Hu Zhiyong , Wang Guoping
Published: March 2012

Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41‐year‐old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well‐circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal‐like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal‐like immunophenotype.
Lower physical activity, but not excessive calorie intake, is associated with metabolic syndrome in elderly with type 2 diabetes mellitus: The Japanese elderly diabetes intervention trial
Authors: Iijima Katsuya , Iimuro Satoshi , Ohashi Yasuo , Sakurai Takashi , Umegaki Hiroyuki , Araki Atsushi , Yoshimura Yukio , Ouchi Yasuyoshi , Ito Hideki ,   the Japanese Elderly Diabetes Intervention Trial Study Group
Published: March 2012

Aim:  A decline in physical activity has been shown to be associated with metabolic syndrome (MetS), leading to cardiovascular events. However, this is difficult to manage well in the elderly with multiple atherosclerotic risk factors. In this study, we investigated the correlation between physical activity and clinical parameters in the presence and absence of MetS in Japanese elderly subjects with type 2 diabetes mellitus (T2DM). In addition, we determined which factor, calorie intake or physical activity, mainly contributes to the prevalence of MetS.

Methods:  Cross‐sectional analysis of 846 consecutive Japanese elderly (408 men and 438 women, mean age 68.7 years) was carried out at the time of enrolment (2000–2002) in the Japanese Elderly Diabetes Intervention Trial. Their level of physical activity was evaluated using the Baecke questionnaire, consisting of three components: work, sports and leisure. Total activity score (TAS) as the sum of each activity score was divided into four quartiles (Q1 to Q4).

Results:  After adjustment for age and sex, there was a positive association of TAS with high‐density lipoprotein cholesterol, although no significant correlation between other lipid parameters and TAS was found. In addition, fasting plasma glucose, insulin level and physical measurements, such as waist circumference, waist/hip ratio and body mass index, were inversely associated with TAS. Although no correlation between TAS and cognitive function Mini‐Mental State Examination was found, TAS was positively associated with instrumental ADL and negatively associated with geriatric depression score (GDS), suggesting that a decline in physical activity in the elderly is associated with depressed mood rather than a decline of cognitive function. Total calorie intake appeared to increase according to TAS; however, this did not reach statistical significance. In a subanalysis comparing the presence and absence of MetS, the TAS grade in the MetS group was significantly lower than that in the non‐MetS group, although there was no significant difference in total calorie intake between the groups.

Conclusion:  These results showed that lower physical activity, but not excessive calorie intake, is independently associated with the prevalence of MetS in the elderly with T2DM. In our routine work, encouraging physical activity might contribute to preventing MetS and subsequent atherosclerotic disease in the elderly, rather than strict management of abnormal laboratory parameters using multiple drugs. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 68–76.
The impact of continuous subcutaneous insulin infusion on glycaemic control in children and adolescents: a regional review in North East England using a bio‐modelling approach
Authors: Sinha A. , Thomas M. F. , Rushton S. P. , Cheetham T.
Published: March 2012

Diabet. Med. 29, 1342–1343 (2012)
Understanding lacunar stroke: also an epidemiological challenge
Authors: Béjot Yannick
Published: March 2012

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Time Course of Adenosine‐Induced Pulmonary Vein Reconnection after Isolation: Implications for Mechanism of Dormant Conduction
Authors: CHEUNG JIM W. , CHUNG JEFFREY H. , Ip JAMES E. , MARKOWITZ STEVEN M. , LIU CHRISTOPHER F. , THOMAS GEORGE , LERMAN BRUCE B.
Published: March 2012

Background:

Adenosine (ADO) has been proposed to reconnect isolated pulmonary veins (PVs) postablation through hyperpolarization of damaged myocytes in an animal model. However, PV reconnection can occur via ADO‐mediated sympathetic activation. We sought to determine the mechanism of ADO‐induced PV reconnection in the clinical setting by characterizing its time course and location in patients undergoing PV isolation.

Methods:

Seventy‐four patients (61 male; age 61 ± 10 years) undergoing PV isolation for atrial fibrillation (54 [73%] paroxysmal and 19 [27%] persistent) were studied. After each PV was isolated, a 12‐mg intravenous bolus of ADO was administered and onset, offset, and location of ADO‐induced PV reconnection and onset and offset of bradycardia were analyzed.

Results:

In 22 (30%) patients, ADO‐induced PV reconnection occurred in 34 of 270 (13%) PVs. In 24 (71%) PVs, the duration of ADO‐induced reconnection exceeded that of bradycardia. The onset of ADO‐induced reconnection occurred before the onset of bradycardia in 10 (30%) PVs and during bradycardia in 23 (70%) PVs. No PVs exhibited onset of reconnection after resolution of bradycardia. Common sites of PV reconnection included the carinal region (41% of right PVs and 29% of left PVs) and left PV‐atrial appendageal ridge region (35% of left PVs).

Conclusions:

ADO‐induced PV reconnection occurs during the bradycardic phase of the ADO bolus response and not during the late tachycardic phase. ADO‐induced PV dormant conduction is closely associated with the negative dromotropic effects of ADO and suggests that hyperpolarization of the resting membrane is the unifying mechanism. (PACE 2012;XX:1–8)
The Use of Advance Directives among Patients with Implantable Cardioverter Defibrillators
Authors: TAJOURI TANYA H. , OTTENBERG ABIGALE L. , HAYES DAVID L. , MUELLER PAUL S.
Published: March 2012

Background:

We aimed to determine the prevalence of advance directives (ADs) among patients with implantable cardioverter defibrillators (ICDs) and of ADs that addressed ICD management at the end of life.

Methods:

The medical records of all patients who underwent ICD implantation during 2007 at a single institution were reviewed retrospectively to determine the number of patients with an AD and the number of ADs mentioning the ICD specifically (i.e. ICD management at end of life).

Results:

During 2007, 420 patients (males, 71%) underwent ICD implantation at our institution (mean age [range] at implantation, 63 [1–90] years). Primary prevention was the most common indication for device therapy (254 patients [61%]). Overall, 127 patients (30%) had an AD, with 83 ADs (65%) completed more than 12 months before ICD implantation and 10 (8%) completed after it. Several life‐sustaining treatments were mentioned in the ADs: tube feeding, 46 (37%); cardiopulmonary resuscitation, 25 (20%); mechanical ventilation, 22 (17%); and hemodialysis, nine (7%). Pain control was mentioned in 58 ADs (46%) and comfort measures in 38 (30%). However, only two ADs (2%) mentioned the ICD or its deactivation at end of life.

Conclusions:

About one‐third of patients with ICDs had an AD, but only a couple ADs mentioned the ICD. These results suggest that clinicians should not only encourage patients with ICDs to complete an AD, but also encourage them to address ICD management specifically. Not addressing ICD management in an AD may result in ethical dilemmas during end‐of‐life care. (PACE 2012; xx; 1–7)
Three‐Dimensional Analysis and Computer Modeling of the Capillary Endothelial Vesicular System with Electron Tomography
Authors: WAGNER ROGER , MODLA SHANNON , HOSSLER FRED , CZYMMEK KIRK
Published: March 2012

Please cite this paper as: Wagner R, Modla S, Hossler F, Czymmek K. Three‐dimensional analysis and computer modeling of the capillary endothelial vesicular system with electron tomography. Microcirculation 19: 477–484, 2012.

Objective:  We examined the three‐dimensional organization of the endothelial vesicular system with TEM tomography of semi‐thick sections.

Materials and methods:  Mouse abdominal muscle capillaries were perfused with terbium to label vesicular compartments open to the luminal surface. The tissue was prepared for TEM and semi‐thick (250 nm) sections were cut. Dual axis tilt series, collected from +60° to −60° at 1° increments, were acquired in regions of labeled abluminal caveolae. These tomograms were reconstructed and analyzed to reveal three‐dimensional vesicular associations not evident in thin sections.

Results:  Reconstructed tomograms revealed free vesicles, both labeled and unlabeled, in the endothelial cytoplasm as well as transendothelial channels that spanned the luminal and abluminal membranes. A large membranous compartment connecting the luminal and abluminal surfaces was also present. Computer modeling of tomographic data and video animations provided three‐dimensional perspectives to these structures.

Conclusions:  Uncertainties associated with other three‐dimensional methods to study the capillary wall are remedied by tomographic analysis of semi‐thick sections. Transendothelial channels of fused vesicles and free cytoplasmic vesicles give credence to their role as large pores in the transport of solutes across the walls of continuous capillaries.