bluuebunny/crossref_metadata_2025 huggingface dataset:
Isotope‐guided Surgery for Nonpalpable Breast Cancer
Authors: Chow Man Po , Hung Wai Ka , Chu Tiffany , Lui Chun Ying , Ying Marcus , Mak Kong Ling , Chan Miranda
Published: October 2010

Background

The hook‐wire technique is used to guide surgical excision of nonpalpable breast lesions. Recently, isotope has been used to guide the excision, and when sentinel node biopsy is performed during the same operation, the procedure is termed Sentinel Node and Occult Lesion Localization (SNOLL). We evaluated the use of this procedure for nonpalpable cancers in Chinese women.

Methods

Seventy‐four patients underwent SNOLL before breast‐conserving surgery. Intratumoral injection of sulfur colloid and lymphoscintigraphy (LSG) were performed. A gamma probe was used for resection planning and localization of the sentinel node (SN). Blue dye mapping was used in patients with negative LSG. Complete excision was defined as a tumor‐free margin greater than 1 mm.

Results

The primary breast lesion was successfully removed in 73 patients (99%). Complete excision was achieved in 61 patients (82%). Drainage to axilla was detected by LSG in 53 patients (72%). The gamma probe was more sensitive than LSG and had an 82% SN identification rate. Patients with a positive LSG had a higher chance of SN localization by gamma probe than patients with a negative LSG (100% vs. 38%, p < 0.001). In patients with a negative LSG, supplementary blue dye mapping increased the SN localization rate from 38 to 90%. The SN identification rate was 97% in the whole series.

Conclusion

Isotope‐guided surgery was reliable, with a 99% localization rate for nonpalpable breast lesions and an 82% SN localization rate. The success rate of SN identification could be improved to 97% with the addition of blue dye mapping for patients with negative drainage on lymphoscintigraphy.
Enzyme replacement therapy for mucopolysaccharidosis VI—experience in Taiwan
Authors: Lin Hsiang‐Yu , Chen Ming‐Ren , Chuang Chih‐Kuang , Chen Chih‐Ping , Lin Dar‐Shong , Chien Yin‐Hsiu , Ke Yu‐Yuan , Tsai Fuu‐Jen , Pan Hui‐Ping , Lin Shio‐Jean , Hwu Wuh‐Liang , Niu Dau‐Ming , Lee Ni‐Chung , Lin Shuan‐Pei
Published: October 2010

Information regarding the clinical outcome of enzyme replacement therapy (ERT) with recombinant human N‐acetylgalactosamine 4‐sulfatase (rhASB) for mucopolysaccharidosis (MPS) VI in Asian patients is limited. We reviewed nine Taiwanese patients with MPS VI (four males and five females; age range 1.4–21.1 years) treated with weekly intravenous infusions of rhASB (1.0 mg/kg) for at least 2 years. We assessed the biochemical and clinical response every 3 months. After 2 years of treatment, seven patients experienced improvement over baseline in the 6‐min walk by a mean of 69.3 m (27.3%), and seven also increased the 3‐min stair climb by a mean of 47 steps (35.7%). Shoulder range of motion in all patients improved, and Joint Pain and Stiffness Questionnaire scores improved by 0.597 points (30.5%). Four patients had improved pulmonary function [forced expiratory volume in 1 s increased by 0.130 L (26.3%) and forced vital capacity by 0.148 L (27.6%)]. The respiratory disturbance index decreased in the four patients who underwent polysomnography. A mean overall 51% decrease in urinary glycosaminoglycan excretion indicated a satisfactory biochemical response. ERT was well tolerated by all patients. This treatment is thus beneficial and appears to be safe for treatment of MPS VI in Taiwanese patients.
In Situ Synthesis of Reduced Graphene Oxide and Gold Nanocomposites for Nanoelectronics and Biosensing
Authors: Dong Xiaochen , Huang Wei , Chen Peng
Published: October 2010

In this study, an in situ chemical synthesis approach has been developed to prepare graphene–Au nanocomposites from chemically reduced graphene oxide (rGO) in aqueous media. UV–Vis absorption, atomic force microscopy, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy were used to demonstrate the successful attachment of Au nanoparticles to graphene sheets. Configured as field-effect transistors (FETs), the as-synthesized single-layered rGO-Au nanocomposites exhibit higher hole mobility and conductance when compared to the rGO sheets, promising its applications in nanoelectronics. Furthermore, we demonstrate that the rGO-Au FETs are able to label-freely detect DNA hybridization with high sensitivity, indicating its potentials in nanoelectronic biosensing.
Quantification of the energy required for the destruction ofBalanus amphitritelarva by ultrasonic treatment
Authors: Seth Nishant , Chakravarty Piyul , Khandeparker Lidita , Anil Arga Chandrashekar , Pandit Aniruddha B.
Published: October 2010

Ultrasonic treatment, a relatively less explored technology in water disinfection, was used to quantify the energy required for the destruction of larvae of barnacleBalanus amphitrite, which is a major marine fouling and a potential invasive organism. Since the power used and treatment time for disinfection are economically, and practically, the most important parameters, the energy required to pulverize the larvae into pieces ≤30 µm was determined as a function of the acoustic power density. The present investigation suggests that an ultrasonic system operating at 20 kHz and 0.0975 W/cm3can effectively pulverize barnacle larvae having length (~440 µm) and breadth (~350 µm) within 45 seconds using 0.1 mJ/larva of pulverization energy. It was also observed that following pulverization of the larvae, the bacterial abundance increased and the rate of release of bacteria was dependent on power level and treatment time, which in turn decided the pulverization rate and hence the rate of release of bacteria.
Maintaining high rates of measles immunization in Africa
Authors: LESSLER J. , MOSS W. J. , LOWTHER S. A. , CUMMINGS D. A. T.
Published: October 2010

Supplementary immunization activities (SIAs) are important in achieving high levels of population immunity to measles virus. Using data from a 2006 survey of measles vaccination in Lusaka, Zambia, we developed a model to predict measles immunity following routine vaccination and SIAs, and absent natural infection. Projected population immunity was compared between the current programme and alternatives, including supplementing routine vaccination with a second dose, or SIAs at 1-, 2-, 3-, 4- and 5-year intervals. Current routine vaccination plus frequent SIAs could maintain high levels of population immunity in children aged <5 years, even if each frequent SIA has low coverage (e.g. ⩾72% for bi-annual 60% coverage SIAsvs. ⩾69% for quadrennial 95% coverage SIAs). A second dose at 12 months with current coverage could achieve 81% immunity. Circulating measles virus will only increase population immunity. Public health officials should consider frequent SIAs when resources for a two-dose strategy are unavailable.
The double challenge of adapting to climate change while accelerating development in sub-Saharan Africa
Authors: HASSAN RASHID
Published: October 2010

Accelerating economic growth and social development is necessary to reduce the vulnerability and enhance the adaptive capacity of sub-Saharan Africa to cope with the consequences of predicted unfavorable future climate. This requires major investments and policy reforms to induce a needed radical transformation of the way development is currently pursued to a more climate-sensitive path of low carbon growth. Key gaps in the current knowledge base that call for major investments and urgent attention include the ability to forecast more robust local future climate and to account for the uncertainties associated with climate risks for ecosystems' functions and probable nonconvexities in future impacts to project more plausible scenarios for future development in sub-Saharan Africa and provide better information on the costs and benefits of potential actions to avert the negative consequences of climate change.
Measuring sustainability under regime shift uncertainty: a resilience pricing approach
Authors: MÄLER KARL-GÖRAN , LI CHUAN-ZHONG
Published: October 2010

This paper is concerned with the theory of resilience pricing and sustainability measurement in the presence of risk for regime shift in a dynamic economy–environment system. Following Holling (Annual Review of Ecology and Systematics, vol. 4, 1973, pp. 1–23), we consider resilience as the maximal perturbation that the system can absorb without flipping into a qualitatively different state. Using a multisector growth model under uncertainty, we derive the shadow price of resilience that affects the probabilities of the system to flip in the future. We also analyze the role of resilience on sustainability with both ex-ante and ex-post welfare measures.
The economics of biodiversity: the evolving agenda
Authors: PERRINGS CHARLES
Published: October 2010

This paper assesses how the economics of biodiversity, as a field, has evolved in response to developments in biodiversity science and policy over the life of the journal,Environment and Development Economics. Several main trends in the economics of biodiversity are identified. First, biodiversity change has come to be analyzed largely through its impact on ecosystem services (in the sense of the Millennium Ecosystem Assessment). Second, there has been a growing focus on factors that optimally lead to biodiversity decline, i.e., the benefits to be had from reducing the abundance of pests, predators, pathogens, and competitors. Third, increasing attention is being paid to two global drivers of biodiversity change, climate and global economic integration, and the effect they have on the distribution and abundance of both beneficial and harmful species. Fourth, there has been growing interest in the development of instruments to deal with the transboundary public good aspect of biodiversity, and in particular in the development of payments for ecosystem services. The paper identifies the influence of these trends on attempts to model the role of biodiversity in the production of goods and services.
A Multiscale Approach to Assess the Complex Surface of Polyurethane Catheters and the Effects of a New Plasma Decontamination Treatment on the Surface Properties
Authors: Mrad Omar , Saunier Johanna , Aymes-Chodur Caroline , Rosilio Véronique , Bouttier Sylvie , Agnely Florence , Aubert Pascal , Vigneron Jacky , Etcheberry Arnaud , Yagoubi Najet
Published: October 2010

Polyurethane catheters made of Pellethane 2363-80AE® were treated with a low temperature plasma developed for the decontamination of reusable polymer devices in hospitals. We investigated the modifications of the polymer surface by studying the topographic modifications, the chemical modifications, and their consequences on the wettability and bacterial adhesion. This study showed that plasma treatment modified the topography and grafted oxygen and nitrogen species onto the surface, resulting in an increase in the surface polarity. This effect could be correlated to the number of nitrogen atoms interacting with the surface. Moreover, this study demonstrated the significance of multiscale heterogeneities, and the complexity of industrial medical devices made from polymers. Their surface can be heterogeneous, and they contain additives that can migrate and change the surface composition.
Excitation of airwaves caused by bubble bursting in a cylindrical conduit: Experiments and a model
Authors: Kobayashi Tsukasa , Namiki Atsuko , Sumita Ikuro
Published: October 2010

Strombolian eruptions are considered to be a consequence of the bursting of a large bubble. In order to understand the relation between the style of bubble bursting and the resulting airwave, we perform experiments of bubble bursting at the top of the surface of viscous liquid contained in an acrylic pipe which acts as an air column and observe it visually and acoustically. We find that when the liquid viscosity is less than 1 Pa s, the bubble vibrates before bursting. The major source of the airwave during the sequence of the bubble bursting is the bubble vibration. On the other hand, when the liquid viscosity is greater than 1 Pa s, the bubble does not vibrate. During bubble bursting, an aperture appears on the bubble film. The aperture growth first accelerates and later decelerates before finally stopping. The major source of the airwave is the aperture growth. We calculate a synthetic waveform of the airwave generated by the aperture growth which explains the experimentally observed airwave well. When the frequency of the airwave generated by the aperture growth matches the eigenfrequency of the air column, resonance occurs. Applying this model to the Strombolian eruption, the characteristic low frequency (<20 Hz) is explained if the velocity of the aperture growth is several meters per second. The model also explains the asymmetrical initial rise of the airwave observed in the Strombolian eruptions as a result of the accelerating growth of the aperture.
A new velocity field for Greece: Implications for the kinematics and dynamics of the Aegean
Authors: Floyd M. A. , Billiris H. , Paradissis D. , Veis G. , Avallone A. , Briole P. , McClusky S. , Nocquet J.‐M. , Palamartchouk K. , Parsons B. , England P. C.
Published: October 2010

A new set of geodetic velocities for Greece and the Aegean, derived from 254 survey‐mode and continuous GPS sites, is used to test kinematic and dynamic models for this area of rapid continental deformation. Modeling the kinematics of the Aegean by the rotation of a small number (3–6) of blocks produces RMS misfits of ∼5 mm yr−1 in the southern Aegean and western Peloponnese, indicating significant internal strain within these postulated blocks. It is possible to fit the observed velocities to within 2–3 mm yr−1 (RMS) by models that contain 10 or more blocks, but many such models can be found, with widely varying arrangements of blocks, that fit the data equally well provided that the horizontal dimension of those blocks is not larger than 100–200 km. A continuous field of velocity calculated from the GPS velocities by assuming that strain rates are homogeneous on the scale of ∼120 km fits the observed velocities to better than 2–3 mm yr−1 (RMS), with systematic misfits, representing more localized strain, confined to a region approximately 100 × 100 km in size around the western Gulf of Corinth. This velocity field accounts for the major active tectonic features of Greece and the Aegean, including the widespread north‐south extensional deformation and the distributed strike‐slip deformation in the NE Aegean and western Greece. The T axes of earthquakes are aligned with the principal axes of elongation in the geodetic field, major active normal fault systems are perpendicular to those axes, and ∼90% of the large earthquakes in this region during the past 120 years took place within the areas in which the geodetic strain rate exceeds 30 nanostrain yr−1. These observations suggest that the faulting within the upper crust of the Aegean region is driven by forces that are coherent over a scale that is significantly greater than 100 km. It is likely that those forces arise primarily from differences in gravitational potential energy within the lithosphere of the region.
Increase of wintertime fog in China: Potential impacts of weakening of the Eastern Asian monsoon circulation and increasing aerosol loading
Authors: Niu Feng , Li Zhanqing , Li Can , Lee Kwon‐Ho , Wang Minyan
Published: October 2010

Fog is a severe weather hazard that greatly influences traffic and daily life with potentially heavy economic loss. An increasing number of traffic accidents caused by fog have been reported in China in recent years. In this study, we show that the frequencies of fog events in wintertime over eastern‐central China have doubled over the past three decades. For the same period, surface wind speeds have dropped from 3.7 m/s to about 3 m/s and the mean number of cold air outbreaks has decreased from 7 to around 5 times per winter; relative humidity and the frequency of light wind events have also increased significantly. Weakening of the East Asian winter monsoon system appears to be responsible for these changes. The weakened East Asian winter monsoon circulation brings less cold and dry air to the region, reduces wind speed, and favors the formation of fog. The regional increase in atmospheric aerosol loading may also change the regional circulation pattern, creating favorable conditions for fog. This hypothesis is tested using the National Centers for Environmental Prediction (NCEP) reanalysis data and model simulations with the National Center for Atmospheric Research Community Climate Model (NCAR/CCM3). The analyses show that the 500hPa trough in East Asia has shallowed over the past three decades. Meanwhile, the surface Siberian high has weakened which is likely the cause for the diminishment in speed of the prevailing northwesterly winds and the reduction in intrusions of dry and cold air from the northwest. The increase in atmospheric aerosols was shown to heat the atmosphere and generates a cyclonic circulation anomaly over eastern‐central China. This circulation anomaly also leads to a reduction in the influx of dry and cold air over eastern‐central China. These effects are responsible for the increased convergence of water vapor therein. All these changes favor the formation and maintenance of fog over this region.
Dissolved CO2 in small catchment streams of eastern Amazonia: A minor pathway of terrestrial carbon loss
Authors: Davidson Eric A. , Figueiredo Ricardo O. , Markewitz Daniel , Aufdenkampe Anthony K.
Published: October 2010

Production of carbon dioxide (CO2) in soils can lead to supersaturation of dissolved free CO2 (pCO2) in groundwater, which later evades to the atmosphere as groundwater enters streams and rivers. This process could be a significant pathway for return of terrestrially fixed C to the atmosphere. We measured pCO2 monthly over two years at multiple stations along three streams from their headwaters in remnant mature forests through multiple land covers in Pará, Brazil. The pCO2 averaged 19,000 μatm in headwaters and decreased to about 4,500 μatm downstream. Similar values were measured in headwaters of two small pristine mature forest catchments. Two approaches were used to estimate groundwater pCO2 evasion: assuming that headwater pCO2 measurements reflected incoming groundwater pCO2 or that all entering stream water was in equilibrium with previously measured deep soil CO2. With these assumptions, losses from the terrestrial environment through aquatic evasion of pCO2 would be 0.02–0.15 Mg C ha−1 of land area yr−1, which is about 2–3 orders of magnitude lower than annual estimates of soil respiration and net primary productivity. However, downstream pCO2 values that appear to be in quasi‐steady state indicate contributions from other C sources, such as aquatic primary production, soil erosion, dissolved organic matter, or litter inputs from streamside vegetation. Hence, lateral pCO2 loss from groundwater to streams is minor for most of the terrestrial ecosystems of this region, although C loss to streams could be significant for net terrestrial budgets in riparian ecosystems or areas experiencing erosion.
Effect of sediment and nutrient loading on Lake Tahoe optical conditions and restoration opportunities using a newly developed lake clarity model
Authors: Sahoo G. B. , Schladow S. G. , Reuter J. E.
Published: October 2010

A quasi‐two‐dimensional lake clarity model (LCM) was developed to better understand the impacts of pollutant load on lake/reservoir water quality and to provide guidelines for lake/reservoir management and restoration. Though the LCM can be applied to any lake, the model was calibrated and validated using the available detailed data set of Lake Tahoe. The estimated and measured annual average Secchi depths demonstrate a very high degree of agreement with relative error of less than 6%. The sensitivity analysis was performed on those parameter(s)/load(s) found to have a large effect on lake clarity. Loading and settling rates of fine inorganic particles (<16 μm in diameter) were found to have the largest effect on lake clarity. Atmospheric load adds inorganic particles and nutrients to the surface layer, thus directly affecting lake clarity. Since maximum chlorophyll a concentration is observed in deep water (approximately 50 m below surface) during spring and summer, the Secchi depth (approximately 20–22 m) was found to be relatively insensitive to the change in chlorophyll a concentration in this deep layer. The model was used to simulate different load reduction scenarios to help answer questions such as how much load reduction is needed to restore Lake Tahoe's historic clarity of approximately 30 m and how quickly this change can be achieved? The LCM provides a firsthand scientific solution to managers that the historic clarity can be achieved if total reduction of nutrients and inorganic particles loads will be reduced to approximately 55% from all sources or approximately 75% from urban sources.
Strong seismic shaking of randomly prestressed brittle rocks, rock damage, and nonlinear attenuation
Authors: Sleep Norman H.
Published: October 2010

Strong seismic waves produce frequent episodes of transient oscillating dynamic stress in the shallow subsurface within seismically active areas. Dynamic stress drives slip on a network of preexisting small fracture planes and leaves residual stresses once shaking ceases. The residual stresses act as prestresses during the next strong earthquake. Local failure occurs on fractures at low dynamic stresses where the prestresses are favorably aligned, while most of the bulk rock remains intact. Hence nonlinear attenuation of strong seismic waves commences at dynamic stresses well below those for pervasive Coulomb failure. Consideration of the fractal distribution of prestresses indicates that nonlinear attenuation increases rapidly with dynamic stress. Vertically propagating shear waves provide simple scaling relationships for quick application: (1) Nonlinear attenuation is concentrated near the quarter wavelength depth. (2) The Coulomb stress ratio (dynamic/lithostatic stress) above the quarter wavelength depth scales with the sustained dynamic acceleration in g's. Rate and state friction thus provides estimates of the maximum sustained acceleration from Coulomb stress ratio at failure: ∼1 for regolith that has repeatedly failed, ∼1.5 for shallow intact sandstone, and ∼2 for shallow intact granite. A potentially observable effect occurs with shallow brittle regolith on hillslopes where gravity causes net downslope creep during strong shaking. Analogous crack network behavior with prestress occurs in the damage zone surrounding the rupture zone of major faults. Pulverized rock forms at shallow depths when rock is repeatedly deformed in strong shaking to just beyond the elastic limit, but strain does not localize into a crack network.
Electrostatic solitary waves associated with magnetic anomalies and wake boundary of the Moon observed by KAGUYA
Authors: Hashimoto K. , Hashitani M. , Kasahara Y. , Omura Y. , Nishino M. N. , Saito Y. , Yokota S. , Ono T. , Tsunakawa H. , Shibuya H. , Matsushima M. , Shimizu H. , Takahashi F.
Published: October 2010

We present observations of electrostatic solitary waves (ESWs) near the Moon by SELENE (KAGUYA) in the solar wind and in the lunar wake. SELENE is a lunar orbiter with an altitude of 100 km and measured wave electric field, background magnetic field, and fluxes of ions and electrons, etc. ESWs are categorized into three types depending on different regions of observations: ESWs generated by electrons reflected and accelerated by an electric field in the wake boundary (Type A), strong ESWs generated by bi‐streaming electrons mirror‐reflected over the magnetic anomaly (Type B), and ESWs generated by reflected electrons when the local magnetic field is connected to the lunar surface (Type C). ESWs of Type C often alternate with Langmuir waves.
Ultrashallow seismic imaging of the causative fault of the 1980, M6.9, southern Italy earthquake by pre‐stack depth migration of dense wide‐aperture data
Authors: Bruno Pier Paolo , Castiello Antonio , Improta Luigi
Published: October 2010

A two‐step imaging procedure, including pre‐stack depth migration (PSDM) and non‐linear multiscale refraction tomography, was applied to dense wide‐aperture data with the aim of imaging the causative fault of the 1980, M6.9, Irpinia normal faulting earthquake in a very complex geologic environment. PSDM is often ineffective for ultrashallow imaging (100 m of depth and less) of laterally heterogeneous media because of the difficulty in estimating a correct velocity model for migration. Dense wide‐aperture profiling allowed us to build accurate velocity models across the fault zone by multiscale tomography and to record wide‐angle reflections from steep reflectors. PSDM provided better imaging with respect to conventional post‐stack depth migration, and improved definition of fault geometry and apparent cumulative displacement. Results indicate that this imaging strategy can be very effective for near‐surface fault detection and characterization. Fault location and geometry are in agreement with paleoseismic data from two nearby trenches. The estimated vertical fault throw is only 29–38 m. This value, combined with the vertical slip rate determined by trench data, suggests a young age (97–127 kyr) of fault inception.
Ionospheric tomography by combining vertical and oblique sounding data with TEC retrieved from a tri‐band beacon
Authors: Zhao Hai‐Sheng , Xu Zheng‐Wen , Wu Jian , Wang Zhan‐Ge
Published: October 2010

The development of the tri‐band beacon brings hope to the high‐resolution computerized ionospheric tomography (CIT) imaging. This is a major motivation for the proposed launch of a Chinese satellite carrying as a key payload a tri‐band beacon for seismological studies. Due to the limited‐angle geometry, the vertical precision of CIT still needs to be improved to meet the requirements of some applications, such as monitoring the ionospheric behaviors before earthquakes. To solve this problem, this paper puts forward a new bi‐iteration method, which combines vertical and oblique sounding data with the total electron content (TEC) retrieved from an onboard tri‐band beacon of a planned Chinese satellite for seismological studies transmitting VHF, UHF, and L‐band frequencies. A ground‐based high‐resolution ionospheric observation network was built in northern China in April 2009. Based on this ground network and the planned satellite, high‐resolution ionospheric structures can be reconstructed in real time for monitoring the ionospheric precursors of earthquakes over several seismic belts in northern China. The numerical simulations show that electron density distributions reconstructed from the three‐frequency TEC are significantly improved after incorporating observation data of the ground‐based vertical and oblique ionograms. Here, the oblique sounding data are assimilated in the CIT for the first time. The results in this paper help to ensure that the measurements to be made by this solid network will yield their potential.
Coral evidence for earthquake recurrence and an A.D. 1390–1455 cluster at the south end of the 2004 Aceh–Andaman rupture
Authors: Meltzner Aron J. , Sieh Kerry , Chiang Hong‐Wei , Shen Chuan‐Chou , Suwargadi Bambang W. , Natawidjaja Danny H. , Philibosian Belle E. , Briggs Richard W. , Galetzka John
Published: October 2010

Coral records of relative sea level change provide a history of vertical interseismic and coseismic deformation along the coast of northern Simeulue Island, Sumatra, and reveal details about earthquakes in the 10th and 14th–15th centuries A.D. along the southern end of the December 2004 Mw 9.2 Sunda megathrust rupture. Over a 56 year period between A.D. 1390 and 1455, northern Simeulue experienced a cluster of megathrust ruptures, associated with total uplift that was considerably more than in 2004. Uplifted corals at two sites constrain the first event of the cluster to A.D. 1393 ± 3 and 1394 ± 2 (2σ). A smaller but well‐substantiated uplift occurred in northern Simeulue in 1430 ± 3. An inferred third uplift, in A.D. 1450 ± 3, killed all corals on the reef flats of northern Simeulue. The amount of uplift during this third event, though confirmed only to have exceeded 28 and 41 cm at two sites, probably surpassed the 100 and 44 cm that occurred, respectively, at those sites in 2004, and it was likely more than in 2004 over all of northern Simeulue. The evidence for past earthquake clustering combined with the inference of considerably greater uplift in A.D. 1390–1455 than in 2004 suggests that strain may still be stored along the southernmost part of the 2004 rupture. Interseismic subsidence rates recorded by northern Simeulue coral microatolls have varied by up to a factor of 4 at some sites from one earthquake cycle to another.
The Discovery of the Dipeptidyl Peptidase-4 (DPP4) Inhibitor Onglyza™: From Concept to Market
Authors: Robl Jeffrey A. , Hamann Lawrence G.
Published: October 2010

Utilizing modern principles of rational drug design originally pioneered by Miguel Ondetti and David Cushman in the discovery of captopril, the team at Bristol-Myers Squibb discovered saxagliptin (Onglyza™), a small-molecule peptidomimetic inhibitor of dipeptidyl peptidase-4 (DPP4). The unique constellation of features exhibited by this compound (low molecular weight, high DPP4 potency, slow-tight binding kinetics, high enzymatic selectivity, good pharmacokinetics and a superior pharmacodynamic response) enabled its advancement in clinical trials, where it demonstrated a robust efficacy and safety profile in the treatment of type-2 diabetes. As a result, saxagliptin was granted marketing approval in both the US and the EU in 2009. This chapter outlines the discovery efforts and thought principles utilized in the conception, design, and discovery of saxagliptin and its progression to registration as a new, safe and effective drug for the treatment of diabetes.
The Discovery of the Long-acting PDE5 Inhibitor PF-489791 for the Treatment of Pulmonary Hypertension
Authors: Bell Andrew S. , Palmer Michael J.
Published: October 2010

Clinical studies with our male erectile dysfunction medicine, sildenafil, identified several additional indications for PDE5 inhibitors. Since these include disease indications requiring chronic treatment and/or single dose daily dosing in order to be competitive, we sought novel agents with an excellent safety profile, and in particular, no potential for off-target activity against other PDE family members.

We were able to identify a second generation PDE5 agent meeting these requirement based on a HTS–derived series. Key elements in discovery were the focus on physicochemistry and pharmacokinetics throughout the programme, together with the use of co-crystal structure data to guide design and identification of a parallel chemistry amenable, wide synthetic scope template. These elements enabled rapid discovery of a proprietary lead 3 with inherently good physicochemistry, a novel aminopyridine pharmacophore and PDE6 selectivity. Further optimisation provided advanced acidic, neutral and basic leads. Finally, a potent and selective acidic clinical candidate 13 with low clearance and an outstanding safety profile was identified. The excellent pre-clinical profile derived from our property-based strategy has successfully translated to once daily oral pharmacokinetics in man.
From HTS to Market: the Discovery and Development of Maraviroc, a CCR5 Antagonist for the Treatment of HIV
Authors: Barber Chris , Pryde David
Published: October 2010

AIDS has claimed the lives of over 25 million people, driving the continuing desire to identify new treatments for this devastating disease. Maraviroc, the first CC Chemokine Receptor 5 (CCR5) antagonist to be licensed as a treatment for HIV, works by blocking cellular entry by the virus through CCR5. This chapter describes the rationale for the approach and the medicinal chemistry that eventually led to the discovery of maraviroc, including the removal by design of unwanted CYP2D6 and hERG activity. The use of structure-based drug design to develop follow-on agents and series is also described. Clinical data for maraviroc are provided, and the development of other CCR5 antagonists discovered across the pharmaceutical industry is summarized.
2′-F-2′-C-Methyl Nucleosides and Nucleotides for the Treatment of Hepatitis C Virus: from Discovery to the Clinic
Authors: Sofia Michael J. , Furman Phillip A. , Symonds William T.
Published: October 2010

Hepatitis C virus (HCV) is believed to have infected over 170 million individuals worldwide and is considered a global health problem. Infection with HCV is known to lead to chronic liver disease, cirrhosis and eventually hepatocellular carcinoma. The search for direct-acting antiviral agents that inhibit the replication of HCV has focused on the HCV non-structural proteins of which the NS5B RNA-dependent RNA polymerase is one. Nucleoside inhibitor strategies have proven fruitful in the identification of potent and selective inhibitors of HCV polymerase. The 2′-F-2′-C-methyl class of nucleos(t)ides have proved particularly useful in that this class of nucleos(t)ides show good potency, selectivity, broad genotype coverage and demonstrate a high barrier to resistance. RG7128 and PSI-7851 are members of the 2′-F-2′-C-methyl class of nucleos(t)ides. RG7128 is an ester prodrug of PSI-6130, a cytidine nucleoside, and has demonstrated potent clinical efficacy in genotype 1,2,3 and 4 patients. RG7128 is currently in Phase IIb clinical study. PSI-7851, a liver targeting prodrug, has demonstrated clinical efficacy and an acceptable safety profile in genotype 1 patients. The discovery and clinical development of RG7128 and PSI-7851 are presented.
Polymer–Clay Nanocomposite Particles by Direct and Inverse Emulsion Polymerization
Authors: Ming Weihua (Marshall) , Voorn Dirk-Jan , van Herk Alex M.
Published: October 2010

Polymer/clay nanocomposite particles are particles with at least one component being structured on the nanoscale, and are anticipated to be used in coatings, adhesives, and films for barrier properties. In this chapter we will focus on three areas of research leading to polymer/clay nanocomposite particles: use of nascent clay as the stabilizing agent in direct emulsion polymerization, use of hydrophobized clay as the stabilizing agent in inverse emulsion polymerization, and encapsulation of exfoliated clay platelets via emulsion polymerization.
Acrylic–Clay Nanocomposites by Suspension and Emulsion Polymerization
Authors: Šebenik URŠka , Krajnc MatjaŽ
Published: October 2010

This chapter is focused on the synthesis and properties of acrylic/clay nanocomposite pressure-sensitive adhesives (PSA), which are an example of use of low glass transition temperature acrylic/clay nanocomposite materials. These acrylic/clay nanocomposites can be synthesized in situ, by carrying out an emulsion or suspension (co)polymerization of a chosen monomer or monomers in the presence of clay. The properties of a PSA depend upon balance of three basic adhesive properties: tack, peel strength, and shear resistance. Hence, to be an effective PSA, the material needs a balance of elasticity and viscosity. Here it is shown how the incorporation of nanosized clay into PSA latex film offers an effective means to modify the viscoelastic properties of PSA, with the aim of optimizing the adhesive properties. The adhesive properties are changed according to the specific end use of the adhesive and can be adjusted by choosing an appropriate nanocomposite synthesis method and by using the proper type and amount of clay.
Biodegradable Polymer–Clay Nanocomposite Fire Retardants via Emulsifier-free Emulsion Polymerization
Authors: Sahoo Prafulla Kumar
Published: October 2010

Poly(butyl acrylate) (PBA)/sodium silicate (SS) nanocomposites were prepared via emulsifier-free emulsion technique in presence of Cu(II)/glycine chelate complex and ammonium persulfate (APS) initiator. The strongly hydrophobic PBA was intercalated into the hydrophilic SS layer. Since the interlayers of silicate were filled with sodium cations, the hydrophilic properties were enhanced and lead to high degree of swelling. The formation of the PBA/SS nanocomposite was confirmed by infrared spectra (IR). Furthermore, as evidenced by transmission electron microscopy (TEM), the composite so obtained was found to have nanoscale structure. X-ray diffraction (XRD) was used to characterize the nanoscale dispersion of the layer silicate and useful for measurement of d-spacing in interlayer system. It was found from thermogravimetric analysis that PBA/SS nanocomposites had more thermal stability as compared to raw PBA due to intercalation. Burning test of the nanocomposites performance exhibited a flame retardant property, which was also verified from cone calorimeter analysis. For its commercialization, the ecological friendly nature was studied via biodegradation and was found to have better biodegradability than the raw PBA.
PAN–Silica–Clay Nanocomposites by Emulsion Polymerization
Authors: Cai Chunhua , Lin Jiaping , Wei Lan
Published: October 2010

Polymer nanocomposites have great advantages for important applications due to their impressive enhancements of material properties. The most studied nanocomposites contain only one type of nanofiller, very few studies on the nanocomposites with two types of nanofillers were performed. The generation of synergistic effect of the two nanofillers with different shapes was found to exhibit profound enhancement effect on the property of the polymer matrix. For the preparation method of the nanocomposites, in situ emulsion polymerization is an effective way to prepare exfoliated clay nanocomposites. In this review, we discuss the structure and property of PAN/clay/silica ternary component nanocomposites prepared by in situ emulsion polymerization in water. Clay, without surface modification, was successfully exfoliated in PAN matrix. The thermal and mechanical properties of PAN/clay/SiO2 ternary nanocomposites are significantly enhanced relative to the PAN/clay and PAN/SiO2 binary systems.
Polymer–Clay Nanocomposite Particles and Soap-free Latexes Stabilized by Clay Platelets: State of the Art and Recent Advances
Authors: Bourgeat-Lami Elodie , Sheibat-Othman Nida , Dos Santos Amilton Martins
Published: October 2010

Recent advances in synthesis of polymer/clay nanocomposites by heterophase polymerisation in aqueous dispersed media are briefly reviewed in this chapter. Particular emphasis is given to emulsion polymerisation and to the ability to produce polymer/clay nanocomposites with controlled nanostructures. A focus is also given on the influence of these nanostructures on the final properties of the composite materials. Besides conventional emulsion polymerisation, increasing interest into the synthesis of clay-armoured latexes produced in the absence of surfactant has emerged in the recent literature. This review highlights recent developments in this area which have contributed to a deeper understanding of the mechanism of particle formation. Important breakthroughs including the production of high solids content latexes and latex films with enhanced mechanical properties are reported and discussed. Finally, process features and modelling are introduced to show their interest in the comprehension of the reaction mechanisms and the optimisation of the operating conditions.
What Do You Mean By That? Constructive Beginnings When Working With Adolescents With Language Learning Disabilities
Authors: Wallach Geraldine P. , Charlton Stephen , Christie Julie
Published: October 2010

The authors recognize the challenges facing school-based speech-language pathologists (SLPs) who are encouraged to create and deliver curriculum-focused and strategic-based intervention. The high school setting can be an especially daunting one but it is also a place where SLPs can use their expertise to participate in innovative partnerships with students and colleagues in the facilitation of language and literacy learning. This article outlines selected language initiates focused toward content area learning within a constructive comprehension framework.
The Urgent Need to Address Workforce Readiness in Adolescent Literacy Intervention
Authors: Ehren Barbara J. , Murza Kimberly
Published: October 2010

The literacy skills adolescents now need to be successful in school and the workplace are much different from those of 20 years ago. Today, adolescents must engage in high literacy to achieve in the competitive, 21st century, global marketplace. In this article, the authors discuss workforce readiness as a framework for delivering literacy intervention that has the potential to make a significant impact on the success of adolescents who struggle. They address specific contributions of speech-language pathologists in this arena.
Magnetic resonance imaging after operative repair of Achilles tendon rupture
Authors: Maffulli N. , Thorpe A. P. , Smith F. W.
Published: October 2010

We performed a magnetic resonance imaging (MRI) study in 16 consecutive patients who had undergone open repair of a unilateral Achilles tendon rupture (ATR) at an average of 32.5 (SD 3.2) (range 29–36) months from the operation. We measured the widest antero‐posterior diameter of the tendon, the longest distance between the insertion of the Achilles tendon on the calcaneum and the musculo‐tendinous junction of the soleus muscle on the Achilles tendon, the distance between the insertion of the Achilles tendon on the calcaneum and the point of maximal width of the tendon. We also ascertained whether areas of altered signal were present in and around the tendon. The operated tendons were always significantly thicker than the non‐operated ones. There was a non‐significant trend for the other measurements to be greater in the operated tendons. In five patients, areas of dishomogeneous signal were present in the operated tendon. These areas were less than 25% of the antero‐posterior diameter of the tendon, and were clinically silent. These findings probably represent normal features of long‐term tendon healing following open repair of an ATR.
There are differences in early morbidity after ACL reconstruction when comparing patellar tendon and semitendinosus tendon graft
Authors: Eriksson K. , Anderberg P. , Hamberg P. , Olerud P. , Wredmark T.
Published: October 2010

The main objective of this study was to study solely early postoperative morbidity following anterior cruciate ligament (ACL) reconstruction by comparing the gold standard procedure, the bone‐patellar tendon‐bone graft (BTB), and one of the most common alternatives, the semitendinosus tendon graft (ST). The prospective study included 107 randomized patients (50 BTB and 57 ST). The follow‐up period was set to 20–35 weeks postoperatively (mean 26.8±3.5 weeks). One patient suffered early graft rupture and 89 (84%) of the remaining 106 patients were able to attend the follow‐up within the given time limit. There were no differences in sick leave between the groups. The Lysholm score, Tegner activity level score and Visual Analog Scales (VAS) with the questions “How does your knee function?” and “How does your knee affect your activity level?” revealed no differences between the groups. Subjective patellofemoral pain, patellofemoral compartment findings and donor site morbidity were more common in the BTB group, P<0.05. Lachman test grade 1+ was more common in the ST group, P<0.05, but there was no significant difference in instrumented Lachman side‐to‐side comparison. The ST group scored better in the one‐leg hop test than the BTB group, P<0.05. No correlations between these clinical and functional findings and subjective knee function scores were found. In conclusion, ACL reconstruction with ST tendon graft presented fewer short‐term postoperative problems as compared to reconstruction with BTB.
Investigation of potential and electric field profiles in cross sections of CdTe/CdS solar cells using scanning Kelvin probe microscopy
Authors: Moutinho H. R. , Dhere R. G. , Jiang C.-S. , Yan Yanfa , Albin D. S. , Al-Jassim M. M.
Published: October 2010

We investigated cross sections of working CdTe/CdS solar cells using scanning Kelvin probe microscopy (SKPM). The cross sections were prepared by polishing to avoid steps between the glass substrate and film that generally make the analysis difficult. However, this process resulted in strong pinning of the Fermi level. During the measurements, the cells were biased under different conditions, revealing the distribution of the electrical potential inside the device. We were able to identify different regions inside the device: in the region away from the CdTe/CdS junction, there was only a small variation in the potential; closer to the junction, the potential increased, due to the increase in the depletion regions with the reverse bias; at the junction, there was a sudden increase in the potential, which was attributed to interdiffusion between CdTe and CdS. By taking the first derivative of the potential, we were able to calculate the electric field inside the device. The maximum of the electric field, which locates the p-n junction, occurred at the interface between CdTe and CdS. However, the electric field at this location had a strong peak, in agreement with the existence of the interdiffusion layer, with higher doping, at the junction. The presence of this layer was confirmed by transmission electron microscopy. We also investigated the distribution of the potential and electrical field inside a CdTe/SnO2 device, without the CdS layer, and showed that the interdiffusion does not happen in this case. Finally, we used Poisson’s equation to estimate the doping inside the CdTe film in both devices.
Development of an x-ray imaging system for the Laser Megajoule (LMJ)
Authors: Turk G. , Reverdin C. , Gontier D. , Darbon S. , Dujardin C. , Ledoux G. , Hamel M. , Simic V. , Normand S.
Published: October 2010

This imaging system aims at recording images of the core size and shape of an imploding deuterium-tritium (DT) microballoon on LMJ inertial confinement fusion (ICF) experiments. Image acquisition is difficult due to the harsh surrounding created by the fusion reaction, which affects system specifications. This one is made of a scintillator, an optical relay, and a CCD camera shielded from the surrounding. The system was tested on different facilities at CEA/DIF, where a spatial resolution of 120 μm was achieved and gamma dose up to 20 rad effects were measured. Setup and performed test are described.
Multifrequency channel microwave reflectometer with frequency hopping operation for density fluctuation measurements in Large Helical Device
Authors: Tokuzawa T. , Ejiri A. , Kawahata K.
Published: October 2010

In order to measure the internal structure of density fluctuations using a microwave reflectometer, the broadband frequency tunable system, which has the ability of fast and stable hopping operation, has been improved in the Large Helical Device. Simultaneous multipoint measurement is the key issue of this development. For accurate phase measurement, the system utilizes a single sideband modulation technique. Currently, a dual channel heterodyne frequency hopping reflectometer system has been constructed and applied to the Alfvén eigenmode measurements.
Contrasting magnetic behavior of Ni50Mn35In15 and Ni50Mn34.5In15.5 alloys
Authors: Chattopadhyay M. K. , Manekar M. A. , Sharma V. K. , Arora Parul , Tiwari Pragya , Tiwari M. K. , Roy S. B.
Published: October 2010

We have studied the electrical resistivity, magnetization, and heat capacity of the off-stoichiometric Heusler alloys Ni50Mn35In15 and Ni50Mn34.5In15.5 as functions of temperature and magnetic field. The results show that the alloy system is more sensitive to the composition than what is apparent from the established phase diagram. We have found that the ground states as well as the nature of phase transitions strongly depend on concentration differences as low as 0.5 at. %. While in the case of Ni50Mn34.5In15.5 we do observe a magnetic field induced martensite to austenite phase transition, there is no detectable signature of any field induced transition in the Ni50Mn35In15 alloy even up to fields as high as 80 kOe. Accordingly, the functional properties of these two alloys are also drastically different.