bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival in patients with metastatic recurrent breast cancer after adjuvant chemotherapy
Authors: Tevaarwerk Amye J. , Gray Robert J. , Schneider Bryan P. , Smith Mary Lou , Wagner Lynne I. , Fetting John H. , Davidson Nancy , Goldstein Lori J. , Miller Kathy D. , Sparano Joseph A.
Published: October 2012

BACKGROUND:

Population‐based studies have shown improved survival for patients diagnosed with metastatic breast cancer over time, presumably because of the availability of new and more effective therapies. The objective of the current study was to determine whether survival improved for patients who developed distant recurrence of breast cancer after receiving adjuvant therapy.

METHODS:

Adjuvant chemotherapy trials coordinated by the Eastern Cooperative Oncology Group that accrued patients between 1978 and 2002 were reviewed. Survival after distant disease recurrence was estimated for progressive time periods, and adjusted for baseline covariates in a Cox proportional hazards model.

RESULTS:

Of the 13,785 patients who received adjuvant chemotherapy in 11 trials, 3447 (25%) developed distant disease recurrence; the median survival after recurrence was 20 months (95% confidence interval, 19 months‐21 months). Factors associated with inferior survival included a shorter distant recurrence‐free interval (DRFI), estrogen receptor‐negative and progesterone receptor‐negative disease, the number of positive axillary lymph nodes present at the time of diagnosis, and black race (P < .0001 for all). When the time period of recurrence was added to the model, it was not found to be significantly associated with survival for the general population with disease recurrence. Survival improved over time only in those patients with hormone receptor‐negative disease with a DRFI ≤ 3 years, both among the 5 most recent and the entire trial data sets (P = .01 and P = .05, respectively).

CONCLUSIONS:

In contrast to reports from population‐based studies, no general improvement in survival was observed over the last 30 years for patients who developed distant disease recurrence after adjuvant chemotherapy after adjusting for DRFI. Improved survival for patients with hormone receptor‐negative disease with a short DRFI suggests a benefit from trastuzumab. Cancer 2013. © 2012 American Cancer Society.
A score to identify patients with metastatic spinal cord compression who may be candidates for best supportive care
Authors: Rades Dirk , Hueppe Michael , Schild Steven E.
Published: October 2012

BACKGROUND:

The objective of the current study was to develop a scoring system that identifies those patients with metastatic spinal cord compression who may be candidates for best supportive care or single‐fraction radiotherapy.

METHODS:

Ten potential prognostic factors were retrospectively analyzed in 2029 patients, including age, gender, Eastern Cooperative Oncology Group performance status, tumor type, number of involved vertebrae, further bone metastases, visceral metastases, interval from time of cancer diagnosis to the development of MSCC, time to the development of motor deficits, and ambulatory status.

RESULTS:

On multivariate analysis, Eastern Cooperative Oncology Group performance status, tumor type, bone metastases, visceral metastases, interval from cancer diagnosis to the development of metastatic spinal cord compression, time to the development of motor deficits, and ambulatory status were found to be significantly associated with survival. The risk score represented the sum of the scores for each of these factors, obtained from the probability of the patient dying within 2 months (shown as the percentage) divided by 10. Risk scores ranged between 6 and 25 points. At a cutoff value of ≥ 24 points, the specificity was 99.8% and the positive predictive value was 96.0%, which indicates that approximately 4% of the patients predicted to die within 2 months survived > 2 months.

CONCLUSIONS:

This score identifies patients who have a very poor survival with a high specificity and a high positive predictive value. Patients with a score of ≥ 24 points have a very high probability of dying within 2 months. Thus, overtreatment with intensive therapies can be avoided in these patients, who are very unlikely to benefit.Cancer 2013. © 2012 American Cancer Society.
Short‐term outcomes of craniotomy for malignant brain tumors in the elderly
Authors: Seicean Andreea , Seicean Sinziana , Schiltz Nicholas K. , Alan Nima , Jones Paul K. , Neuhauser Duncan , Weil Robert J.
Published: October 2012

BACKGROUND.

Disparity in resection rates for malignant brain tumors in elderly patients is partially attributed to a belief that advanced age is associated with an increased risk of postoperative morbidity and mortality. The objective of this study was to investigate the effect of advanced age (≥75 years) on 30‐day outcomes in patients with primary and metastatic brain tumors who underwent craniotomy for definitive resection of a malignant brain tumor.

METHODS.

The authors conducted prospective analyses of the American College of Surgeons' National Surgical Quality‐Improvement Project (NSQIP) database from 2006 to 2010 of 970 patients aged ≥40 years who underwent craniotomy for definitive resection of neoplasm. Preoperative and intraoperative characteristics and 30‐day outcomes were stratified by age. By using propensity scores, 134 patients (aged ≥75 years) were matched to 134 patients ages 40 to 74 years. Logistic regression was used to predict adverse postoperative outcomes.

RESULTS.

The median length of hospital stay was 5 days; the rate of minor and major complications were 5.9% and 13.1%, respectively; 5.7% of patients returned to the operating room; and 4.3% of patients died within 30 days. Advanced age did not increase the odds for poorer short‐term outcomes.

CONCLUSIONS.

Advanced age did not increase the risk of poor outcomes after surgical resection of primary or metastatic intracranial tumors when analyses were controlled for other risk factors. These results suggest that age should not be used, in isolation, as an a priori factor to discourage pursuing craniotomy. Cancer 2013. © 2012 American Cancer Society.
Resonance Raman Spectral Imaging of Intracellular Uptake of β‐Carotene Loaded Poly(D,L‐lactide‐co‐glycolide) Nanoparticles
Authors: Matthäus Christian , Schubert Stephanie , Schmitt Michael , Krafft Christoph , Dietzek Benjamin , Schubert Ulrich S. , Popp Jürgen
Published: October 2012

The use of nanoparticles for drug delivery has been drawing considerable attention in pharmaceutical research. With increasing diversity and potential of various carrier systems, it is important to study the impact of nanocarriers on sub‐cellular metabolic processes and organelles, since the delivery of a drug usually involves intra‐cellular internalization. Herein, we employ Raman microscopy as a non‐invasive method for cellular and sub‐cellular imaging, to monitor the uptake and translocation patterns of particles based on poly(D,L‐lactide‐co‐glycolide) over time. As the technique detects inherent signals from the molecules of interest, it does not rely on external labels or dyes, which is an advantage over fluorescence labeling. For this purpose, the particles were loaded with β‐carotene. The conjugated π‐system of the molecule has a large Raman scattering cross‐section and gives rise to resonance Raman effects, which can enhance the sensitivity by orders of magnitude. β‐Carotene as a provitamin is not soluble in water and is thus usually of low bioavailability, which is enhanced by encapsulation into the nanoparticles.
Effect of External Electric Field on H‐Bonding and π‐Stacking Interactions in Guanine Aggregates
Authors: Jissy Akkarapattiakal K. , Datta Ayan
Published: October 2012

The structure and electronic properties of guanine oligomers and π stacks of guanine quartets (G‐quartets) with circulene are investigated under an external field through first‐principles calculations. An electric field induces nonplanarity in the guanine aggregates and also leads to an increase in the H‐bond distances. The calculations reveal that the binding energy of the circulenes with G‐quartets increases on application of an electric field along the stacking direction. The HOMO–LUMO gap decreases substantially under the influence of an external field. The contribution of a simple dipole–dipole interaction to the stability of the stacked system is also analyzed. The electric field along the perpendicular axis increases the dipole moments of the guanine dimer, trimer, and quartet. Such an increase in the dipole moment facilitates stacking with circulenes. The stability of G‐quartet–circulene π stacks depends on the phase of the dipole moment (in‐phase or out‐of‐phase) induced by an external electric field. The stability of stacks of bowl‐shaped circulenes with G‐quartets depends on the direction of the applied field.
A reliable and energy‐efficient routing protocol for underwater wireless sensor networks
Authors: Wahid Abdul , Lee Sungwon , Kim Dongkyun
Published: October 2012

Recently, underwater wireless sensor networks (UWSNs) have attracted much research attention to support various applications for pollution monitoring, tsunami warnings, offshore exploration, tactical surveillance, etc. However, because of the peculiar characteristics of UWSNs, designing communication protocols for UWSNs is a challenging task. Particularly, designing a routing protocol is of the most importance for successful data transmissions between sensors and the sink. In this paper, we propose a reliable and energy‐efficient routing protocol, named R‐ERP2R (Reliable Energy‐efficient Routing Protocol based on physical distance and residual energy). The main idea behind R‐ERP2R is to utilize physical distance as a routing metric and to balance energy consumption among sensors. Furthermore, during the selection of forwarding nodes, link quality towards the forwarding nodes is also considered to provide reliability and the residual energy of the forwarding nodes to prolong network lifetime. Using the NS‐2 simulator, R‐ERP2R is compared against a well‐known routing protocol (i.e. depth‐based routing) in terms of network lifetime, energy consumption, end‐to‐end delay and delivery ratio. The simulation results proved that R‐ERP2R performs better in UWSNs.Copyright © 2012 John Wiley & Sons, Ltd.
Energie‐ und Ressourceneffizienz von Gebäuden aus Kalksandstein
Authors: Vogdt Frank Ulrich , Schäfers Martin
Published: October 2012

Der Beitrag zeigt anhand von exemplarischen Ein‐ und Mehrfamilienhäusern in Mauerwerksbauweise, dass auch zukünftig national und europäisch angestrebte energetische Standards technisch problemlos mit Kalksandstein realisiert werden können. Hier erweist sich das von der KS‐Industrie entwickelte Konstruktionsprinzip der Funktionstrennung als besonders zukunftsweisend, da eine weitere Verbesserung des baulichen Wärmeschutzes ressourcenschonend durch eine einfache Erhöhung der Wärmedämmstoffdicke möglich wird.

Im Rahmen einer Lebenszyklusanalyse ergibt sich bei einer Verschärfung der energetischen Standards darüber hinausgehend eine positive ökologische Bilanz mit geringen Anteilen für Aufwendungen (z. B. Primärenergieaufwand) und Wirkungen (z. B. Emissionen von Treibhausgasen, wie CO2) aufgrund der hohen Ressourceneffizienz von KS. Ökonomisch ist nach derzeitigem Stand der Technik bzw. nach derzeitigem Preisgefüge für Bauprodukte und Energie ein über den moderaten Passivhausstandard hinausgehender Standard wie der “Nahezu‐Null‐Energie‐Haus‐Standard“ noch nicht wirtschaftlich. Dies ist jedoch nicht auf die KS‐Wandkonstruktionen sondern vielmehr auf die aufwendigere technische Gebäudeausstattung TGA, insbesondere zur Nutzung regenerativer Energie, zurückzuführen.

Resource efficiency of calcium silicate buildings. By means of two exemplarily regarded buildings (one family house and one apartment building) with masonry construction, the present article depicts, that future requirements, which will result from national and European legislation, can be realised with constructions of calcium silicate without any technical difficulties. In this context, exterior walls with separated functional layers, which were developed by the German calcium silicate industry turn to be particularly forward‐looking, due to the fact, that a further enhancement of the thermal insulation of such constructions can easily be realised by increasing the thickness of the insulating material.

The results of a life‐cycle assessment show that higher energy standards of buildings lead to reduced ecological impacts (for example emission of green house gas like CO2) along the whole life cycle of the building compared to lower energy standards due to the high resource efficiency of calcium silicate constructions. In an economical point of view, higher building‐energy standards than moderate passive house standard like nearly zero energy standard are not profitable at present if current price levels for building products and energy are considered. This does not result from calcium silicate wall constructions but particular from elaborated building technologies, especially for the generation of energy from renewable resources.
In Würde altern – Energieeffizienz und Nachhaltigkeit im Wohnungsbau
Authors: Horschler Stefan
Published: October 2012

Anders sieht die Situation im attraktiven Wohnumfeld, mit hohem Wirtschaftspotential und in strukturstarken Gegenden aus; hier wird eine Platzierung der Immobilie am Markt immer möglich sein: allerdings auch ohne eine energetische Optimierung. Außerdem gilt für die Rentabilität einer Immobilie, dass diese möglichst geringe Unterhaltungs‐ und Wartungskosten aufweist. Nachfolgend werden Einzelaspekte des nachhaltigen Bauens aus energetischer, ökonomischer, konstruktiver und baupraktischer Sicht kommentiert.

Aging with dignity – energetic efficiency and sustainability in housing construction. Individuals need to be treated individually – this applies both to humans when it comes to health problems e.g. and to building. Each case for itself demands the definition of the valid criteria for sustainability, even though this may be difficult. For example: Is it economically sensible to establish property with a high level of energetic efficiency up to energetic autonomy at a location, which is urbanistic unattractive, has the outlook of shrinking numbers of inhabitants and therefore no expected further utilization in future? In this case it will be quite difficult to position the object at the market, even though it has its excellent energetic standard. However different will be the situation of an object in an attractive neighbourhood: High economic potential always allows the merchandise of a building, regardless in what energetic shape it comes. For the rentability of a building applies, that costs for maintenance it may be as small costs as possible.

In the following you will find comments on individual aspects of sustainable building from energetic, economic, constructive and practical points of view.
Nachhaltigkeitsanalyse für das Mauerwerksrecycling
Authors: Herbst Tristan , Schneider Sarah , Beck Tabea , Flassenberg Georg
Published: October 2012

In Deutschland fällt mittelfristig eine nicht unerhebliche Menge an Mauerwerksbruch an. Im Sinne einer nachhaltigen Kreislaufwirtschaft sind diese Restmassen zukünftig einem möglichst hochwertigen Recycling zuzuführen. Im Rahmen des IGF‐Forschungsvorhabens 17022 N der Forschungsvereinigung Porenbetonindustrie e.V., Berlin, wird im Gesamtkontext “SIM Stoffkreislauf im Mauerwerksbau“ die Nachhaltigkeit verschiedener Recyclingoptionen für Mauerwerksbruch unter Einbeziehung der Hauptwandbausteinarten Ziegel, Kalksandstein, Porenbeton und Leichtbeton sowie unter Beachtung material‐ und verfahrenstechnischer sowie ökologischer, ökonomischer und sozialer Aspekte ganzheitlich untersucht und bewertet. Auf Grundlage der dabei gewonnenen Erkenntnisse wird ein rechnergestütztes Analysetool zur Nachhaltigkeitsbewertung für das Mauerwerksrecycling entwickelt. Auf diesem Wege sollen im Sinne der aktuellen gesetzlichen Vorgaben nachhaltige Stoffkreisläufe im Mauerwerksbau geschlossen und somit letztlich die Deponierung von Mauerwerksrestmassen vermieden werden.

Sustainability analysis for the recycling of masonry. In Germany, a not unimportant quantity of masonry rubble is generated in the medium term. With regard to a sustainable closed substance cycle waste management, these rest masses have to be recycled if possible. Within the IGF research project “Sustainability Analysis for the Recycling of Masonry”, different recycling options will be assessed with regard to their sustainability performance. In doing so, the main kinds of masonry units (clay units, calcium silicate units, autoclaved aerated concrete units, aggregate concrete units), their material properties, the processing technologies as well as ecological, economic and social aspects will be considered. Based on the results, a web‐based tool will be developed to assess the sustainability of different recycling options for masonry rubble.
Integrale Gebäudeplanung am Beispiel eines Geschossbaus in Ziegelmauerwerk
Authors: Butenweg Christoph , Gellert Christoph
Published: October 2012

Moderne Mauerwerksbauten müssen nach heutigen Anforderungen architektonisch, statisch, energetisch sowie schall‐ und brandschutztechnisch optimal ausgelegt sein. Aufgrund der Komplexität und engen Verzahnung der einzelnen Anforderungen ist eine integrale Gebäudeplanung zur Erzielung einer qualitativ hochwertigen Bauwerkslösung unbedingt notwendig. Diese erfordert von den Fachplanern vertieftes Spezialwissen in den verschiedenen Bereichen, um insbesondere die Schnittstellen und Bauwerksdetails korrekt zu planen und auszuführen. Der Beitrag stellt die integrale Gebäudeplanung am Beispiel eines Geschossbaus in Ziegelbauweise mit Lösungen für wesentliche Detailpunkte vor.

Integral building planning using the example of a multi‐storey clay brick building. Nowadays masonry buildings are optimized to fulfil the requirements on modern buildings with respect to architecture, stability, static, energy efficiency and fire protection. A high quality building can only be achieved with an integral building planning in which the complexity and close connections between the requirements are taken into account. The correct planning and execution of interfaces and building details is a challenge and demands designing engineers with in‐depth knowledge in different application areas. The article introduces the integral building planning on the example of a multi‐storey clay brick building and presents solutions for essential building details.
Qualitätssiegel Nachhaltiger Wohnungsbau – ein Leitfaden und neues Zertifizierungssystem
Authors: Vogler Ingrid
Published: October 2012

Unternehmerische Entscheidungen in der Wohnungswirtschaft müssen sich im Spannungsfeld von sozialen, ökologischen und kulturellen Ansprüchen an den Wohnungsbau und betriebswirtschaftliche Rentabilität bewegen. Diese Dimensionen sind miteinander in Ausgleich zu bringen und keine kann auf Kosten einer anderen maximiert werden. Die Beschreibung und Messung (im Sinne von Benchmarks) von Nachhaltigkeitsaspekten machen nachhaltiges Handeln sichtbar und transparent, stellen aber allein für sich noch nicht automatisch eine nachhaltige Qualität sicher. Die Dokumentation einer nachhaltigen Qualität für neu errichtete Wohngebäude ist aber ein Baustein und Teil eines konsequenten Nachhaltigkeitsmanagements und einer Umsetzung von Nachhaltigkeit als Unternehmensziel. Der Artikel stellt das “Qualitätssiegel Nachhaltiger Wohnungsbau“ vor und führt in einige Aspekte vertiefend ein.

Quality label for sustainable housing – a guide and a new certification system. Management decisions in the housing industry must be taken in the field between social, environmental and cultural requirements of the residential construction and have to be economically efficient. These various dimensions have to be balanced and none of the dimensions can be maximized at the expense of another. The description and measurement (in terms of benchmarks) of sustainability makes sustainable action visible and transparent. But certification by itself does not automatically lead to a sustainable quality. The documentation of a sustainable quality of newly constructed residential buildings is a component and part of a consistent sustainability management and implementation of sustainability as a business objective. The article presents the “quality label sustainable housing”, and introduces some aspects in a more profound level.
Host defense against DNA virus infection in shrimp is mediated by the siRNA pathway
Authors: Huang Tianzhi , Zhang Xiaobo
Published: October 2012

The RNA interference (RNAi) system of eukaryotes using siRNAs has been documented as an immune response against invasion by RNA viruses. However, whether the siRNA pathway can be triggered by the infection with DNA viruses in animals remains to be investigated. In the present study, we show that Marsupenaeus japonicus shrimp can generate an antiviral siRNA (vp28‐siRNA) in response to infection by a double‐stranded DNA virus, white spot syndrome virus (WSSV). After challenging with WSSV, vp28‐siRNA is detected in all the WSSV‐infected organs and tissues of shrimp as early as 24 h postinfection (p.i.). The results indicate that the host Dicer2 and Ago2 proteins are required for the biogenesis and function of vp28‐siRNA, respectively. We show further that vp28‐siRNA predominates in the cytoplasm of shrimp hemocytes at 48 h p.i. Knockdown of Dicer2 by special siRNA or inhibition of vp28‐siRNA with locked nucleic acid antisense oligonucleotides both lead to a significant increase in WSSV copy number at 24–48 h p.i. Our study highlights a novel aspect of the siRNA pathway in the immune response of animals against infection by DNA viruses.
Hybrid PEDOT–Metal Nanoparticles – New Substitutes for PEDOT:PSS in Electrochromic Layers – Towards Improved Performance
Authors: Mumtaz Muhammad , Ouvrard Blanche , Maillaud Laurent , Labrugere Christine , Cloutet Eric , Cramail Henri , Delville Marie‐Helene
Published: October 2012

Hybrid organic–inorganic nanocomposites of poly(3,4‐ethylenedioxythiophene) (PEDOT) and silver or gold {PEDOT–metal (PEDOT–M) nano‐objects (M = Ag, Au) (particle diameter down to 60 nm)} were prepared by a one‐pot oxidative aqueous dispersion polymerization using ammonium persulfate as an oxidant and the corresponding metal salts as co‐oxidant (HAuCl4 and AgNO3) in the presence of pyrrole‐modified‐poly(N‐vinylpyrrolidone‐co‐vinyl alcohol) (PVP‐co‐PVAL‐mod‐Py) stabilizer. The hydrophilic character of such a stabilizer enhances the polymer layer through hydrophilic interactions, which leads to a smooth surface with high wetting properties for subsequent electropolymerizations. PEDOT–M is more conducting than the commercially available PEDOT:PSS, in which the PSS acts as an insulating agent (electrical conductivities up to 1.25 S cm–1). These nanocomposites were used to replace PEDOT:PSS as anchoring layer for further EDOT monomer polymerization, providing an improvement of the electrochromic properties of PEDOT in terms of not only contrast ratio and coloration efficiency but also switching time response.
On the effect of preferential sampling in spatial prediction
Authors: Gelfand Alan E. , Sahu Sujit K. , Holland David M.
Published: October 2012

The choice of the sampling locations in a spatial network is often guided by practical demands. In particular, many locations are preferentially chosen to capture high values of a response, for example, air pollution levels in environmental monitoring. Then, model estimation and prediction of the exposure surface become biased because of the selective sampling. As prediction is often the main utility of the modeling, we suggest that the effect of preferential sampling lies more importantly in the resulting predictive surface than in parameter estimation. We take demonstration of this effect as our focus.

In particular, our contribution is to offer a direct simulation‐based approach to assessing the effects of preferential sampling. We compare two predictive surfaces over the study region, one originating from the notion of an “operating” intensity, driving the selection of monitoring sites, the other under complete spatial randomness. We can consider a range of response models. They may reflect the operating intensity, introduce alternative informative covariates, or just propose a flexible spatial model. Then, we can generate data under the given model. Upon fitting the model and interpolating (kriging), we will obtain two predictive surfaces to compare with the known truth. It is important to note that we need suitable metrics to compare the surfaces and that the predictive surfaces are random, so we need to make expected comparisons. We also present an examination of real data using ozone exposures. Here, what we can show is that, within a given network, there can be substantial differences in the spatial prediction using preferentially chosen locations versus roughly randomly selected locations and that the latter provide much improved predictive validation. Copyright © 2012 John Wiley & Sons, Ltd.
Bayesian spatial–temporal model for cardiac congenital anomalies and ambient air pollution risk assessment
Authors: Warren Joshua , Fuentes Montserrat , Herring Amy , Langlois Peter
Published: October 2012

We introduce a Bayesian spatial–temporal hierarchical multivariate probit regression model that identifies weeks during the first trimester of pregnancy, which are impactful in terms of cardiac congenital anomaly development. The model is able to consider multiple pollutants and a multivariate cardiac anomaly grouping outcome jointly while allowing the critical windows to vary in a continuous manner across time and space. We utilize a dataset of numerical chemical model output that contains information regarding multiple species of PM 2.5. Our introduction of an innovative spatial–temporal semiparametric prior distribution for the pollution risk effects allows for greater flexibility to identify critical weeks during pregnancy, which are missed when more standard models are applied. The multivariate kernel stick‐breaking prior is extended to include space and time simultaneously in both the locations and the masses in order to accommodate complex data settings. Simulation study results suggest that our prior distribution has the flexibility to outperform competitor models in a number of data settings. When applied to the geo‐coded Texas birth data, weeks 3, 7 and 8 of the pregnancy are identified as being impactful in terms of cardiac defect development for multiple pollutants across the spatial domain. Copyright © 2012 John Wiley & Sons, Ltd.
Erosive water level regime and climatic variability forcing of beach–dune systems on south‐western Vancouver Island, British Columbia, Canada
Authors: Heathfield Derek K. , Walker Ian J. , Atkinson David E.
Published: October 2012

Increases in the frequency and magnitude of extreme water levels and storm surges are correlated with known indices of climatic variability (CV), including the El Niño Southern Oscillation (ENSO) and the Pacific Decadal Oscillation (PDO), along some areas of the British Columbia coast. Since a shift to a positive PDO regime in 1977, the effects of ENSO events have been more frequent, persistent, and intense. Teleconnected impacts include more frequent storms, higher surges, and enhanced coastal erosion. The response of oceanographic forcing mechanisms (i.e. tide, surge, wave height, wave period) to CV events and their role in coastal erosion remain unclear, particularly in western Canada. As a first step in exploring the interactions between ocean–atmosphere forcing and beach–dune responses, this paper assembles the historic erosive total water level (TWL) regime and explores relations with observed high magnitude storms that have occurred in the Tofino‐Ucluelet region (Wickaninnish Bay) on the west coast of Vancouver Island, British Columbia, Canada. Extreme events where TWL exceeded an erosional threshold (i.e. elevation of the beach–foredune junction) of 5·5 m aCD are examined to identify dominant forcing mechanisms and to classify a regime that describes erosive events driven principally by wave conditions (61·5%), followed by surge (21·8%), and tidal (16·7%) effects. Furthermore, teleconnections between regional CV phenomena, extreme storm events and, by association, coastal erosion, are explored. Despite regional sea level rise (eustatic and steric), rapid crustal uplift rates have resulted in a falling relative sea level and, in some sedimentary systems, shoreline progradation at rates approaching +1·5 m a–1 over recent decades. Foredune erosion occurs locally with a recurrence interval of approximately 1·53 years followed by rapid rebuilding due to high onshore sand supply and often in the presence of large woody debris and rapidly colonizing vegetation in the backshore. Copyright © 2012 John Wiley & Sons, Ltd.
Kinematics of active earthflows revealed by digital image correlation and DEM subtraction techniques applied to multi‐temporal LiDAR data
Authors: Daehne Alexander , Corsini Alessandro
Published: October 2012

Earthflow‐type landslides are persistent natural hazards having deep socio‐economic and environmental consequences. They have significantly contributed to the geomorphic evolution of mountainous slopes in Europe since the Late Glacial. An understanding of their complex kinematics is crucial to better constrain the processes governing their occurrence and mobility.

In this work we explored the possibility to quantify displacement vectors on a spatially distributed basis and to quantify volumetric transfer at the slope scale with regard to a large flow‐type landslide located in the northern Apennines of Italy. For this purpose we applied digital image correlation (DIC) and digital elevation model differencing (DEMoD) techniques to multi‐temporal airborne LiDAR surveys of 2006, 2007 and 2009.

The DIC was applied to greyscale slope gradient maps retrieved after precise co‐registration of LiDAR surveys. Thereby, movement patterns over various sectors of the landslide were reconstructed and quantified, most notably up to 20 m in the head zone, up to 51 m in the lower main track, and up to about 27 m at the landslide toe. The DEMoD analysis revealed significant mass transfer from the source to the tracks and toe zone, with the upper flow tracks acting as temporal storage of large amounts of material. The mass balance indicated that significant amounts of advancing landslide debris were eroded by a local stream. An integrated analysis of DEMoD and DIC results allowed for a discussion of governing processes, such as the transition from slide to flow, the influence of underlying topography on earthflow mobility, and the role of undrained loading as a mechanism of toe zone reactivation.

In conclusion, the successful application of DIC and DEMoD to the case study underlines the added value of high‐resolution DEMs in the analysis of earthflow kinematics toward a better understanding of their role in the geomorphic evolution of slopes. Copyright © 2012 John Wiley & Sons, Ltd.
Rapid estimation of nuclear magnetic resonance experiment time in low-concentration environmental samples
Authors: Masoom Hussain , Courtier-Murias Denis , Farooq Hashim , Soong Ronald , Simpson Myrna J. , Maas Werner , Kumar Rajeev , Monette Martine , Stronks Henry , Simpson André J.
Published: October 2012

Nuclear magnetic resonance (NMR) spectroscopy is an essential tool for studying environmental samples but is often hindered by low sensitivity, especially for the direct detection of nuclei such as13C. In very heterogeneous samples with NMR nuclei at low abundance, such as soils, sediments, and air particulates, it can take days to acquire a conventional13C spectrum. The present study describes a prescreening method that permits the rapid prediction of experimental run time in natural samples. The approach focuses the NMR chemical shift dispersion into a single spike, and, even in samples with extremely low carbon content, the spike can be observed in two to three minutes, or less. The intensity of the spike is directly proportional to the total concentration of nuclei of interest in the sample. Consequently, the spike intensity can be used as a powerful prescreening method that answers two key questions: (1) Will this sample produce a conventional NMR spectrum? (2) How much instrument time is required to record a spectrum with a specific signal-to-noise (S/N) ratio? The approach identifies samples to avoid (or pretreat) and permits additional NMR experiments to be performed on samples producing high-quality NMR data. Applications in solid- and liquid-state13C NMR are demonstrated, and it is shown that the technique is applicable to a range of nuclei. Environ. Toxicol. Chem. 2013;32:129–136. © 2012 SETAC
A gas‐kinetic scheme for the modified Baer–Nunziato model of compressible two‐phase flow
Authors: Pan L. , Zhao G. P. , Wang S. H.
Published: October 2012

Numerical methods for the Baer–Nunziato model of compressible two‐phase flow have attracted much attention in recent years. In this paper, a two‐phase Bhatnagar–Gross–Krook (BGK) model is constructed in which the non‐conservative terms in the Baer–Nunziato model are considered as the external forces and the collisions both with particles of their phases and other phases are taken into consideration. On the basis of this BGK model, the so‐called modified Baer–Nunziato model is derived and a gas‐kinetic scheme for this modified model is presented. The distribution functions are constructed at the cell interface based on the integral solutions of the BGK equations for both phases. Then, numerical fluxes can be obtained by taking moments of the distribution functions, and non‐conservative terms are explicitly introduced into the construction of numerical fluxes. In this method, not only the iterative processes in the exact Riemann solvers are eliminated but also the collisions with the particles of other phases are taken into account. Copyright © 2012 John Wiley & Sons, Ltd.
Adjustment for Population Stratification via Principal Components in Association Analysis of Rare Variants
Authors: Zhang Yiwei , Guan Weihua , Pan Wei
Published: October 2012

For unrelated samples, principal component (PC) analysis has been established as a simple and effective approach to adjusting for population stratification in association analysis of common variants (CVs, with minor allele frequencies MAF > 5%). However, it is less clear how it would perform in analysis of low‐frequency variants (LFVs, MAF between 1% and 5%), or of rare variants (RVs, MAF < 5%). Furthermore, with next‐generation sequencing data, it is unknown whether PCs should be constructed based on CVs, LFVs, or RVs. In this study, we used the 1000 Genomes Project sequence data to explore the construction of PCs and their use in association analysis of LFVs or RVs for unrelated samples. It is shown that a few top PCs based on either CVs or LFVs could separate two continental groups, European and African samples, but those based on only RVs performed less well. When applied to several association tests in simulated data with population stratification, using PCs based on either CVs or LFVs was effective in controlling Type I error rates, while nonadjustment led to inflated Type I error rates. Perhaps the most interesting observation is that, although the PCs based on LFVs could better separate the two continental groups than those based on CVs, the use of the former could lead to overadjustment in the sense of substantial power loss in the absence of population stratification; in contrast, we did not see any problem with the use of the PCs based on CVs in all our examples.
Endogenous transforming growth factor‐beta promotes quiescence of primary microglia in vitro
Authors: Spittau Björn , Wullkopf Lena , Zhou Xiaolai , Rilka Jennifer , Pfeifer Dietmar , Krieglstein Kerstin
Published: October 2012

Microglia are the immune cells of the central nervous system (CNS) and play important roles under physiological and pathophysiological conditions. Activation of microglia has been reported for a variety of CNS diseases and is believed to be involved in inflammation‐mediated neurodegeneration. Loss of TGFβ1 results in increased microgliosis and neurodegeneration in mice which indicates that TGFβ1 is an important regulator of microglial functions in vivo. Here, we addressed the role of endogenous TGFβ signaling for microglia in vitro. We clearly demonstrate active TGFβ signaling in primary microglia and further introduce Klf10 as a new TGFβ target gene in microglia. Moreover, we provide evidence that microglia express and release TGFβ1 that acts in an autocrine manner to activate microglial TGFβ/Smad signaling in vitro. Using microarrays, we identified TGFβ‐regulated genes in microglia that are involved in TGFβ1 processing, its extracellular storage as well as activation of latent TGFβ. Finally, we demonstrate that pharmacological inhibition of microglial TGFβ signaling resulted in upregulation of the proinflammatory markers IL6 and iNOS and downregulation of the alternative activation markers Arg1 and Ym1 in vitro. Together, these data clearly show that endogenous TGFβ1 and autocrine TGFβ signaling is important for microglial quiescence in vitro and further suggest the upregulation of TGFβ1 in neurodegenerative diseases as a mechanism to regulate microglia functions and silence neuroinflammation. © 2012 Wiley Periodicals, Inc.
Changing Northern catchments: Is altered hydrology, temperature or both going to shape future stream communities and ecosystem processes?
Authors: Friberg Nikolai , Bergfur Jenny , Rasmussen Jes , Sandin Leonard
Published: October 2012

Global change is predicted to increase temperature substantially in the North as well as altering run‐off regimes with less synchronicity as the importance of snow melt declines. River biota and ecosystem processes will be influenced across all levels of organization, both in concert and individually. It is of vital importance that the impacts, and their likely magnitude, can be identified in order to deploy suitable adaptation strategies at the catchment scale. In this paper, we re‐analyse four data sets from studies conducted in Greenland (66–69oN), Iceland (64oN), Sweden (60oN) and Denmark (55–57oN) to try and tease out the likely impacts of water temperature and hydrology in shaping the stream communities and ecosystem processes in high‐latitude catchments. Water temperature was the environmental variable that best explained macroinvertebrate community composition across latitudes. In contrast, no significant relationship between macroinvertebrate community composition and measures of hydraulic stability (or nutrients) was found. We found a strong linear relationship between decay rate of leaf litter and water temperature (r2 = 0.68; p < 0.0001) independent of latitudes. Our study suggests that temperature could be the primary driver of ecosystem change in future with northern catchments likely to be especially vulnerable. Copyright © 2012 John Wiley & Sons, Ltd.
Spinal 5‐HT3 receptors facilitate behavioural hypersensitivity induced by elevated calcium channel alpha‐2‐delta‐1 protein
Authors: Chang E.Y. , Chen X. , Sandhu A. , Li C‐Y. , Luo Z.D.
Published: October 2012

Background

Peripheral nerve injury induces up‐regulation of the calcium channel alpha‐2‐delta‐1 proteins in the dorsal root ganglia and dorsal spinal cord that correlates with neuropathic pain development. Similar behavioural hypersensitivity was also observed in injury‐free transgenic (TG) mice over‐expressing the alpha‐2‐delta‐1 proteins in neuronal tissues. To investigate pathways regulating alpha‐2‐delta‐1 protein‐mediated behavioural hypersensitivity, we examined whether spinal serotonergic 5‐HT3 receptors are involved similarly in the modulation of behavioural hypersensitivity induced by either peripheral nerve injury in a nerve injury model or neuronal alpha‐2‐delta‐1 over‐expression in the TG model.

Methods

The effects of blocking behavioural hypersensitivity in these two models by intrathecal or systemic injections of 5‐HT3 receptor antagonist, ondansetron, were compared.

Results

Our data indicated that the TG mice displayed similar behavioural hypersensitivities to non‐painful mechanical stimulation (tactile allodynia) and painful thermal stimulation (thermal hyperalgesia) as that observed in the nerve injury model. Interestingly, tactile allodynia and thermal hyperalgesia in both models can be blocked similarly by intrathecal, but not systemic, injection of ondansetron.

Conclusions

Our data suggest that spinal 5‐HT3 receptors are likely to play a role in alpha‐2‐delta‐1‐mediated behavioural hypersensitivities through a descending serotonergic facilitation.
Protective effect of curcumin against formaldehyde‐induced genotoxicity in A549 Cell Lines
Authors: Zhang Ben‐Yan , Shi Yu‐Qin , Chen Xin , Dai Juan , Jiang Zhong‐Fa , Li Ning , Zhang Zhi‐Bing
Published: October 2012

Formaldehyde is ubiquitous in the environment. It is known to be a genotoxic substance. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde‐induced genotoxicity in human lung cancer cell lines A549. To test this hypothesis, we investigated the effects of antioxidant on formaldehyde‐induced genotoxicity in A549 Cell Lines. Formaldehyde exposure caused induction of DNA–protein cross‐links (DPCs). Curcumin is an important antioxidant. Formaldehyde significantly increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) activity. In addition, the activation of NF‐κB and AP‐1 were induced by formaldehyde treatment. Pretreatment with curcumin counteracted formaldehyde‐induced oxidative stress, ameliorated DPCs and attenuated activation of NF‐κB and AP‐1 in A549 Cell Lines. These results, taken together, suggest that formaldehyde induced genotoxicity through its ROS and lipid peroxidase activity and caused DPCs effects in A549 cells. Copyright © 2012 John Wiley & Sons, Ltd.
Mollugin inhibits proliferation and induces apoptosis by suppressing fatty acid synthase in HER2‐overexpressing cancer cells
Authors: Do Minh Truong , Hwang Yong Pil , Kim Hyung Gyun , Na MinKyun , Jeong Hye Gwang
Published: October 2012

Mollugin is a naphthohydroquine found in the roots of Rubia cordifolia, and has been reported to have a variety of biological activities, including anti‐inflammatory and apoptotic effects. In the present study, we investigated the molecular mechanisms by which mollugin exerts anti‐tumor effect in HER2‐overexpressing cancer cells. Our results showed that mollugin exhibited potent inhibitory effects on cancer cell proliferation, especially in HER2‐overexpressing SK‐BR‐3 human breast cancer cells and SK‐OV‐3 human ovarian cancer cells in a dose‐ and time‐dependent manner without affecting immortalized normal mammary epithelial cell line MCF‐10A. Furthermore, we found that a blockade of Akt/SREBP‐1c signaling through mollugin treatment significantly reduced FAS expression and subsequently suppressed cell proliferation and induced apoptosis in HER2‐overexpressing cancer cells. Mollugin treatment caused a dose‐dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF‐κB activation. The combination of mollugin with a MEK1/2 inhibitor may be required in order to achieve optimal efficacy in HER2‐overexpressing cancers. These data provide evidence that mollugin inhibits proliferation and induces apoptosis in HER2‐overexpressing cancer cells by blocking expression of the FAS gene through modulation of a HER2/Akt/SREBP‐1c signaling pathway. Our findings suggest that mollugin is a novel modulator of the HER2 pathway in HER2‐overexpressing cancer cells with a potential role in the treatment and prevention of human breast and ovarian cancer with HER2 overexpression. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
Azithromycin suppresses human osteoclast formation and activity in vitro
Authors: Gannon Siobhan C. , Cantley Melissa D. , Haynes David R. , Hirsch Robert , Bartold P. Mark
Published: October 2012

Azithromycin is an antibiotic with anti‐inflammatory properties used as an adjunct to treat periodontitis, a common inflammatory mediated condition featuring pathologic alveolar bone resorption. This study aimed to determine the effect of azithromycin on human osteoclast formation and resorptive activity in vitro. Osteoclasts were generated from peripheral blood mononuclear cells stimulated with macrophage colony stimulating factor (M‐CSF) and receptor activator of nuclear factor kappa B (RANK) ligand. The effects of azithromycin at concentrations ranging from 0.5 to 40 µg/ml were tested. Osteoclast formation and activity, acidification, actin ring formation and expression of mRNA, and protein encoding for key osteoclast genes were assessed. The results demonstrated that azithromycin reduced osteoclast resorptive activity at all concentrations tested with osteoclast formation being significantly reduced at the higher concentrations (20 and 40 µg/ml). mRNA and protein expression of key osteoclast transcription factor Nuclear Factor of Activated T cells (NFATc1) was significantly reduced by azithromycin at later stages of osteoclast development (day 17). Azithromycin also reduced tumor necrosis factor receptor associated factor‐6 (TRAF6) mRNA expression at day 14, and cathepsin K mRNA expression at days 14 and 17. Integrin β3 and MMP‐9 mRNA expression was reduced by azithromycin at day 17 in osteoclasts cultured on dentine. The osteoclast proton pump did not appear to be affected by azithromycin, however formation of the actin ring cytoskeleton was inhibited. This study demonstrates that azithromycin inhibits human osteoclast function in vitro, which may account for at least some of the beneficial clinical effects observed with azithromycin treatment in periodontitis. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
Tumor associated macrophages and neutrophils in tumor progression
Authors: Galdiero Maria R. , Garlanda Cecilia , Jaillon Sébastien , Marone Gianni , Mantovani Alberto
Published: October 2012

Tumor‐associated macrophages (TAMs) are a key component of the tumor microenvironment and orchestrate various aspects of cancer. Diversity and plasticity are hallmarks of cells of the monocyte–macrophage lineage. In response to distinct signals macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a spectrum of activation states. Metabolic adaptation is a key component of macrophage plasticity and polarization, instrumental to their function in homeostasis, immunity and inflammation. Generally, TAMs acquire an M2‐like phenotype that plays important roles in many aspects of tumor growth and progression. There is now evidence that also neutrophils can be driven towards distinct phenotypes in response to microenvironmental signals. The identification of mechanisms and molecules associated with macrophage and neutrophil plasticity and polarized activation provides a basis for new diagnostic and therapeutic strategies. J. Cell. Physiol. 228: 1404–1412, 2013. © 2012 Wiley Periodicals, Inc.