bluuebunny/crossref_metadata_2025_split huggingface dataset:
New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): Mutation within the GDF5 knuckle epitope causes noggin-resistance
Authors: Schwaerzer Gerburg K. , Hiepen Christian , Schrewe Heinrich , Nickel Joachim , Ploeger Frank , Sebald Walter , Mueller Thomas , Knaus Petra 
Published: October 2011

Abstract
Growth and differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) family, is essential for cartilage, bone, and joint formation. Antagonists such as noggin counteract BMP signaling by covering the ligand's BMP type I (BMPRI) and type II (BMPRII, ActRII, ActRIIB) interaction sites. The mutation GDF5-S94N is located within the BMPRII interaction site, the so-called knuckle epitope, and was identified in patients suffering from multiple synostoses syndrome (SYNS). SYNS is characterized by progressive symphalangism, carpal/tarsal fusions, deafness and mild facial dysmorphism. Here we present a novel molecular mechanism of a GDF5 mutation affecting chondrogenesis and osteogenesis. GDF5-S94N exhibits impaired binding to BMPRII causing alleviated Smad and non-Smad signaling and reduced chondrogenic differentiation of ATDC5 cells. Surprisingly, chondrogenesis in mouse micromass cultures was strongly enhanced by GDF5-S94N. By using quantitative techniques (SPR, reporter gene assay, ALP assay, qPCR), we uncovered that this gain of function is caused by strongly reduced affinity of GDF5-S94N to the BMP/GDF antagonist noggin and the consequential lack of noggin inhibition. Thus, since noggin is upregulated during chondrogenic differentiation, GDF5-S94N exceeds the GDF5 action, which results in the phenotypic outcome of SYNS. The detailed molecular characterization of GDF5-S94N as a noggin-resistant growth factor illustrates the potential of GDF5 mutants in applications with defined therapeutical needs. © 2012 American Society for Bone and Mineral Research
Cyr61 expression in osteosarcoma indicates poor prognosis and promotes intratibial growth and lung metastasis in mice
Authors: Sabile Adam A , Arlt Matthias JE , Muff Roman , Bode Beata , Langsam Bettina , Bertz Josefine , Jentzsch Thorsten , Puskas Gabor J , Born Walter , Fuchs Bruno 
Published: October 2011

Abstract
Osteosarcoma is the most frequent primary malignant bone tumor in children and adolescents with a high propensity for lung metastasis, the major cause of disease-related death. Reliable outcome-predictive markers and targets for osteosarcoma metastasis-suppressing drugs are urgently needed for more effective treatment of metastasizing osteosarcoma, which has a current mean 5-year survival rate of approximately 20%. This study investigated the prognostic value and the biological relevance of the extracellular matrix-associated growth factor Cyr61 of the CCN family of secreted proteins in osteosarcoma and metastasis. The prognostic value of Cyr61 was assessed with Kaplan-Meier analyses based on Cyr61 immunostaining of a tissue microarray of osteosarcoma biopsies collected from 60 patients with local or metastatic disease. Effects of Cyr61 overexpression on intratibial tumor growth and lung metastasis of the low metastatic human SaOS-2 osteosarcoma cell line were examined in severe combined immunodeficiency (SCID) mice. Cyr61-provoked signaling was studied in vitro in nonmanipulated SaOS-2 cells. Cyr61 immunostaining of osteosarcoma tissue cores correlated significantly (p = 0.02) with poor patient survival. Mice intratibially injected with Cyr61-overexpressing SaOS-2 cells showed faster tumor growth and an increase in number and outgrowth of lung metastases and consequently significantly (p = 0.0018) shorter survival than mice injected with control SaOS-2 cells. Cyr61-evoked PI-3K/Akt/GSK3β signaling in SaOS-2 cells resulted in a subcellular redistribution of the cell cycle inhibitor p21Cip1/WAF1. Cyr61 has considerable potential as a novel marker for poor prognosis in osteosarcoma and is an attractive target for primary tumor- and metastases-suppressing drugs. © 2012 American Society for Bone and Mineral Research
Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis
Authors: McClung Michael R , Boonen Steven , Törring Ove , Roux Christian , Rizzoli René , Bone Henry G , Benhamou Claude-Laurent , Lems Willem F , Minisola Salvatore , Halse Johan , Hoeck Hans C , Eastell Richard , Wang Andrea , Siddhanti Suresh , Cummings Steven R 
Published: October 2011

Abstract
Denosumab reduces the risk of new vertebral and nonvertebral fractures. Previous trials suggest that the efficacy of antiresorptives on fractures might differ by patients' characteristics, such as age, bone mineral density (BMD), and fracture history. In the FREEDOM study, 7808 women aged 60 to 90 years with osteoporosis were randomly assigned to receive subcutaneous injections of denosumab (60 mg) or placebo every 6 months for 3 years. New vertebral and nonvertebral fractures were radiologically confirmed. Subgroup analyses described in this article were prospectively planned before study unblinding to evaluate the effect of denosumab on new vertebral and nonvertebral fractures across various subgroups. Compared with placebo, denosumab decreased the risk of new vertebral fractures in the overall study population over 3 years. This effect did not significantly differ for any of the nine subgroups analyzed (p &gt; 0.09 for all potential interactions). Denosumab also reduced all nonvertebral fractures by 20% in the full study cohort over 3 years. This risk reduction was statistically significant in women with a baseline femoral neck BMD T-score ≤ −2.5 but not in those with a T-score &gt; −2.5; in those with a body mass index (BMI) &lt; 25 kg/m2 but not ≥ 25 kg/m2; and in those without but not with a prevalent vertebral fracture. These differential treatment effects were not explained by differences in BMD responses to denosumab. Denosumab 60 mg administered every 6 months for 3 years in women with osteoporosis reduced the risk of new vertebral fractures to a similar degree in all subgroups. The effect of denosumab on nonvertebral fracture risk differed by femoral neck BMD, BMI, and prevalent vertebral fracture at baseline. © 2012 American Society for Bone and Mineral Research
Fish out of water: terrestrial jumping by fully aquatic fishes
Authors: Gibb Alice C. , Ashley‐Ross Miriam A. , Pace Cinnamon M. , Long John H. 
Published: October 2011

AbstractMany teleosts that live at the water's edge will voluntarily strand themselves to evade predators or escape poor conditions—this behavior has been repeatedly observed in the field for killifishes (Cyprinodontiformes). Although most killifishes are considered fully aquatic and possess no obvious morphological specializations to facilitate terrestrial locomotion, individuals from several different species have been observed moving across land via a “tail flip” behavior that generates a terrestrial jump. Like aquatic fast starts, terrestrial jumps are produced by high‐curvature lateral flexion of the body (stage one), followed by contralateral flexion of the posterior body (stage two). Here, terrestrial jumps and aquatic fast starts are quantified for two littoral teleosts: Gambusia affinis (a killifish, Cyprinodontiformes) and Danio rerio (a small carp, Cypriniformes) to determine if the tail flip is produced by other (non‐killifish) teleosts and to test the null hypothesis that the tail flip is a fast start behavior, performed on land. Both Danio and Gambusia produce tail flip‐driven terrestrial jumps, which are kinematically distinct from aquatic escapes and characterized by (1) a prolonged stage one, during which the fish bends, lifting and rolling the center of mass over the caudal peduncle, and (2) a relatively brief stage two, wherein the caudal peduncle pushes against the substrate to launch the fish into the aerial phase. The ability of these fully aquatic fishes to employ the same structure to produce distinct kinematic patterns in disparate environments suggests that a new behavior has evolved to facilitate movement on land and that anatomical novelty is not a prerequisite for effective terrestrial locomotion. J. Exp. Zool. 315:649–653, 2011. © 2011 Wiley Periodicals, Inc.
Neuropeptide Y Y1 receptor hippocampal overexpression via viral vectors is associated with modest anxiolytic‐like and proconvulsant effects in mice
Authors: Olesen M.V. , Christiansen S.H. , Gøtzsche C.R. , Nikitidou L. , Kokaia M. , Woldbye D.P.D. 
Published: October 2011

AbstractNeuropeptide Y (NPY) exerts anxiolytic‐ and antidepressant‐like effects in rodents that appear to be mediated via Y1 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY in the hippocampus or amygdala has previously been shown to confer anxiolytic‐like effect in rodents. The present study explored an alternative and more specific approach: overexpression of Y1 receptors. Using a recombinant adeno‐associated viral vector (rAAV) encoding the Y1 gene (rAAV‐Y1), we, for the first time, induced overexpression of functional transgene Y1 receptors in the hippocampus of adult mice and tested the animals in anxiety‐ and depression‐like behavior. Hippocampal Y1 receptors have been suggested to mediate seizure‐promoting effect, so the effects of rAAV‐induced Y1 receptor overexpression were also tested in kainate‐induced seizures. Y1 receptor transgene overexpression was found to be associated with modest anxiolytic‐like effect in the open field and elevated plus maze tests, but no effect was seen on depression‐like behavior using the tail suspension and forced swim tests. However, the rAAV‐Y1 vector modestly aggravated kainate‐induced seizures. These data indicate that rAAV‐induced overexpression of Y1 receptors in the hippocampus could confer anxiolytic‐like effect accompanied by a moderate proconvulsant adverse effect. Further studies are clearly needed to determine whether Y1 gene therapy might have a future role in the treatment of anxiety disorders. © 2011 Wiley Periodicals, Inc.
“Chemische Techniken in die Biochemie tragen”
Authors: Remenyi Christian 
Published: October 2011

Abstract“Chemoselektive Reaktionen für die Synthese und Anwendung funktionaler Proteine” — so lautet der Name eines neuen Schwerpunktprogramms der DFG. Die Nachrichten aus der Chemie fragten zwei der Initiatoren, Christian Hackenberger und Dirk Schwarzer, nach dem Ursprung und den Zielen.
Sprechen Sie Reach?
Authors: Geldsetzer Felix O. 
Published: October 2011

AbstractEinstufungen, Kennzeichnungen und Sicherheitsdatenblätter ändern sich mit den neuen Verordnungen zur Registrierung und Verpackung. Dazu gehören neue Begriffe wie “akut toxisch der Kategorie 1 bis 3” statt “sehr giftig” und “giftig”.
Biomarker für den Zustand einer Zelle
Authors: Poole Jason C. , Gaige Tony , Stupack Jackie , Leonetti Nicole A. , Vilalta Adriαn 
Published: October 2011

AbstractDie Zahl an Mitochondrien in einer Zelle verändert sich als Antwort auf Stimuli, etwa durch Arzneimittel, und zelluläre Zustände. Das Verhältnis von mitochondrialer zu nukleärer DNA ist daher ein Indikator für den metabolischen Status einer Zelle. Quantitative PCR bestimmt präzise den Mitochondriengehalt.
Stroke risk and NSAIDs: a systematic review of observational studies
Authors: Varas‐Lorenzo Cristina , Riera‐Guardia Nuria , Calingaert Brian , Castellsague Jordi , Pariente Antoine , Scotti Lorenza , Sturkenboom Miriam , Perez‐Gutthann Susana 
Published: October 2011

ABSTRACTAimsTo perform a quantitative systematic review of observational studies on the risk of stroke associated with the use of individual NSAIDs.Methods and resultsSearches were conducted using the Medline database within PubMed (1990–2008). Observational cohort or case–control studies were eligible if reported on the risk of cardiovascular events associated with individual NSAIDs versus the nonuse of NSAIDs. We found 3193 articles, in which 75 were eligible for review and abstraction. Of the 75 articles, 6 reported relative risk (RR) of stroke. Data were abstracted into a database using a standardized entry form. Two authors assessed study quality, and discrepancies were resolved by consensus.The pooled RR of all subtypes of incident stroke was increased with the current use of rofecoxib (RR = 1.64, 95% CI = 1.15–2.33) and diclofenac (RR = 1.27, 95% CI = 1.08–1.48). The pooled estimates for naproxen, ibuprofen, and celecoxib were close to unity. The risk of ischemic stroke was also increased with rofecoxib (RR = 1.82, 95% CI = 1.09–3.04) and diclofenac (RR = 1.20, 95% CI = 0.99–1.45). Data were inadequate to estimate the pooled RR by dose and duration, for other individual NSAIDs or nonischemic stroke subtypes.ConclusionThis meta‐analysis supports an increased risk of ischemic stroke with the current use of rofecoxib and diclofenac. Additional studies are required to evaluate most individual NSAIDS, the effect of dose and duration, and the subtypes of stroke. Copyright © 2011 John Wiley & Sons, Ltd.
Sexual adjustment following early stage cervical and endometrial cancer: prospective controlled multi‐centre study
Authors: Juraskova Ilona , Butow Phyllis , Bonner Carissa , Robertson Rosalind , Sharpe Louise 
Published: October 2011

AbstractObjectiveThe primary aim of this study was to investigate objective and subjective aspects of sexual adjustment for women with early stage cervical and endometrial cancer during the first 6 months post‐treatment, compared to women with benign and pre‐invasive gynaecological conditions. ‘Objective’ aspects of sexual function were operationalised as the frequency of sexual activity and ‘subjective’ aspects as the perceived quality of sexual interactions.MethodThis multi‐centre controlled study compared sexual outcomes of women treated for early stage cervical and endometrial cancer (n = 53) with (i) benign gynaecological patients (n = 60), as a comparison group for the physical effects of major pelvic surgery, and (ii) pre‐invasive cancer patients (n = 52), as a comparison group for the emotional effect of the perceived threat of cancer. All patients were assessed at baseline and at 6 months follow‐up using standardised measures of objective and subjective aspects of sexual function, overall satisfaction with sexual life, relationship satisfaction and psychological distress.ResultsDespite experiencing treatment‐related physical changes, women with early stage cervical and endometrial cancer did not report more severe or longer‐lasting sexual sequelae than the benign or pre‐invasive groups. There were no significant differences between the three groups or changes over time for the objective, subjective or overall measures of sexual function, controlling for age, psychological distress and relationship satisfaction.ConclusionThe current findings suggest that early stage cervical and endometrial cancer patients fare as well as benign and pre‐invasive cancer groups in terms of sexual adjustment over the 6 months post‐treatment. Copyright © 2011 John Wiley & Sons, Ltd.
Comments on “An Essay on Contact Angle Measurements”: Determination of Surface Roughness and Modeling of the Wetting Behavior
Authors: Terriza Antonia , Alvarez Rafael , Yubero Francisco , Borras Ana , González‐Elipe Agustin R. 
Published: October 2011

AbstractThis commentary addresses the problem of determining surface roughness values and their use to assess the wetting behavior of surfaces. For very rough surfaces it is shown that depending on the observation scale by atomic force microscopy (AFM) quite different RMS roughness values can be obtained and that only the values taken at saturation can be used for properly describing the roughness of the examined materials. This effect has clear consequences when trying to apply wetting models to account for the influence of roughness on contact angles. These ideas are discussed with examples taken from rough polymer surfaces subjected to plasma etching.magnified image
High efficiency orange‐red phosphorescent organic light emitting diodes based on a Pt(II)‐pyridyltriazolate complex from a structure optimized for charge balance and reduced efficiency roll‐off
Authors: Li Minghang , Lin Ming‐Te , Chen Wei‐Hsuan , McDougald Roy , Arvapally Ravi , Omary Mohammad , Shepherd Nigel D. 
Published: October 2011

AbstractWe report a high power efficiency (PE) of 44.7 ± 0.5 lm/W, high external quantum efficiency (EQE) of 19.7 ± 0.1% at 500 Cd/m2, and efficiency roll‐off of only 4% of the peak value at a useful brightness of 1000 Cd/m2 from orange‐red emitting, organic light emitting diodes featuring 1,1‐bis[(di‐4‐tolylamino)phenyl]cyclohexane (TAPC) as the hole transport layer/electron blocking layer, an emissive layer consisting of 65% bis[3,5‐bis(2‐pyridyl)‐1,2,4‐triazolato]platinum(II) (Pt(ptp)2) doped into 4,4′‐bis(carbazol‐9‐yl)triphenylamine (CBP), and 1,3,5‐tris(phenyl‐2‐benzimidazolyl)‐benzene (TPBI) as the electron transport layer (ETL). Based on a comparison of these structures with devices that did not incorporate an electron/exciton blocker and devices featuring N,N′‐dicarbazolyl‐3,5‐benzene (mCP) as the electron/exciton blocking layer, we ascribe the high efficiency and low efficiency roll‐off to better charge balance, and enhanced confinement of excitons and the recombination zone to the emissive layer.
The precipitation response to the desiccation of Lake Chad
Authors: Lauwaet D. , van Lipzig N. P. M. , Van Weverberg K. , De Ridder K. , Goyens C. 
Published: October 2011

AbstractLocated in the semi‐arid African Sahel, Lake Chad has shrunk from a surface area of 25000 km2 in 1960 to about 1350 km2 due to a series of droughts and anthropogenic influences. The disappearance of such a large open‐water body can be expected to have a noticeable effect on the meteorology in the surroundings of the lake. The impact could extend even further to the west as westward propagating convective systems pass Lake Chad in the rainfall season. This study examines the sensitivity of the regional hydrology and convective processes to the desiccation of the lake using a regional atmospheric model. Three Lake Chad scenarios are applied reflecting the situation in 1960, the current situation and a potential future scenario in which the lake and the surrounding wetlands have disappeared. The model simulations span the months July–September in 2006, which includes the rainfall season in the Lake Chad area. Total precipitation amounts and the components of the hydrological cycle are found to be hardly affected by the existence of the lake. A filled Lake Chad does, however, increase the precipitation at the east side of the lake. The model results indicate that the boundary layer moisture and temperature are significantly altered downwind of the lake. By investigating a mesoscale convective system (MCS) case, this is found to affect the development and progress of the system. At first, the MCS is intensified by the more unstable boundary layer air but the persistence of the system is altered as the cold pool propagation becomes less effective. The proposed mechanism is able to explain the differences in the rainfall patterns nearby Lake Chad between the scenarios. This highlights the local sensitivity to the desiccation of Lake Chad whereas the large‐scale atmospheric processes are not affected. Copyright © 2011 Royal Meteorological Society
Dimensional changes associated with freeze‐drying of the internal elastic lamina from cerebral arteries
Authors: Campbell G. J. , Roach M. R. 
Published: October 2011

AbstractThe shrinkage associated with the freeze‐drying of the internal elastic lamina isolated from human cerebral arteries of various outside diameters has been assessed with the use of a new technique. The net linear shrinkage of freeze‐drying remains essentially constant at 6.9 % ± 0.21 % SE (Standard Error) regardless of the outside diameter of the artery. A comparison of the shrinkage between the circumferential and longitudinal orientations of the tissue did not reveal a statistically significant difference which means that the shrinkage is planar‐isotropic.
SIMSEM—A simulated scanning electron microscope
Authors: Crawford D. , Gerneke D. A. 
Published: October 2011

AbstractA computer‐based simulator for a scanning electron microscope (SEM) has been developed. The simulator, called SIMSEM, is interactive – it teaches students the fundamentals of scanning electron microscopy and the basic methods for operating a SEM in the secondary‐electron or backscattered imaging modes. We anticipate that this type of system will find wide acceptance in SEM laboratories pursuing a policy of research productivity in a multi‐user environment with a high turn‐over of students.In this paper, hardware and software systems in SIMSEM are described and an example of a SIMSEM session is given.
A Mobile Sn Nanowire Inside a β‐Ga2O3 Tube: A Practical Nanoscale Electrically/Thermally Driven Switch
Authors: Zou Rujia , Zhang Zhenyu , Tian Qiwei , Ma Guanxing , Song Guosheng , Chen Zhigang , Hu Junqing 
Published: October 2011

AbstractNanoelectromechanical system switches are seen as key devices for fast switching in communication networks since they can be switched between transmitting and receiving states with an electrostatic command. Herein, the fabrication of practical, nanoscale electrically/thermally driven switches is reported based on a mobile Sn nanowire inside a β‐Ga2O3 tube. The melting point of Sn inside the Ga2O3 tube is found to be as low as 58 °C—far below the value of bulk Sn (231.89 °C)—and its crystal phase (β‐Sn) remains unchanged even at temperatures as low as –170 °C. Thus a miniaturization of the unique wide‐temperature‐range thermometer based on the linear thermal expansion of liquid Sn fillings in the Ga2O3 tube is realized. In addition, the electrical properties of the Sn‐nanowire‐filled β‐Ga2O3 tubes are carefully determined: importantly, the resistance demonstrates a sudden drop (rise) when two Sn nanowires contact (separate), due to the thermally driven motion of the liquid Sn fillings inside the tube. Thus this structure can be switched between its on and off states by controlling the motion, merging or splitting, of the Sn nanowires inside the tube, either electrically, by applying a current, or thermally, at a predetermined temperature.
The DigiHome Service‐Oriented Platform
Authors: Romero Daniel , Hermosillo Gabriel , Taherkordi Amirhosein , Nzekwa Russel , Rouvoy Romain , Eliassen Frank 
Published: October 2011

SUMMARYNowadays, the computational devices are everywhere. In malls, offices, streets, cars, and even homes, we can find devices providing and consuming functionality to improve the user satisfaction. These devices include sensors that provide information about the environment state (e.g., temperature, occupancy, light levels), service providers (e.g., Internet TVs, GPS), smartphones (that contain user preferences), and actuators that act on the environment (e.g., closing the blinds, activating the alarm, changing the temperature). Although these devices exhibit communication capabilities, their integration into a larger monitoring system remains a challenging task, partly because of the strong heterogeneity of technologies and protocols. Therefore, in this article, we focus on home environments and propose a middleware solution, called DigiHome, that applies the Service Component Architecture (SCA) component model to integrate data and events generated by heterogeneous devices in this kind of environments. DigiHome exploits the SCA extensibility to incorporate the REpresentational State Transfer (REST) architectural style and, in this way, leverages on the integration of multiscale systems‐of‐systems (from wireless sensor networks to the Internet). Additionally, the platform applies Complex Event Processing technology that detects application‐specific situations. We claim that the modularization of concerns fostered by DigiHome and materialized in a service‐oriented architecture, makes it easier to incorporate new services and devices in smart home environments. The benefits of the DigiHome platform are demonstrated on smart home scenarios covering home automation, emergency detection, and energy saving situations. Copyright © 2011 John Wiley & Sons, Ltd.