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Showing papers by "Martin Luther University of Halle-Wittenberg published in 2011"


Journal ArticleDOI
TL;DR: A review of the literature and cumulative experience of the multidisciplinary International Neural Monitoring Study Group with IONM spanning nearly 15 years confirms there is little uniformity in application of and results from nerve monitoring across different centers and helps identify areas where additional research is necessary.
Abstract: Intraoperative neural monitoring (IONM) during thyroid and parathyroid surgery has gained widespread acceptance as an adjunct to the gold standard of visual nerve identification. Despite the increasing use of IONM, review of the literature and clinical experience confirms there is little uniformity in application of and results from nerve monitoring across different centers. We provide a review of the literature and cumulative experience of the multidisciplinary International Neural Monitoring Study Group with IONM spanning nearly 15 years. The study group focused its initial work on formulation of standards in IONM as it relates to important areas: 1) standards of equipment setup/endotracheal tube placement and 2) standards of loss of signal evaluation/intraoperative problem-solving algorithm. The use of standardized methods and reporting will provide greater uniformity in application of IONM. In addition, this report clarifies the limitations of IONM and helps identify areas where additional research is necessary. This guideline is, at its forefront, quality driven; it is intended to improve the quality of neural monitoring, to translate the best available evidence into clinical practice to promote best practices. We hope this work will minimize inappropriate variations in monitoring rather than to dictate practice options.

815 citations


Journal ArticleDOI
Jo Ann Banks1, Tomoaki Nishiyama2, Mitsuyasu Hasebe3, Mitsuyasu Hasebe4, John L. Bowman5, John L. Bowman6, Michael Gribskov1, Claude W. dePamphilis7, Victor A. Albert8, Naoki Aono3, Tsuyoshi Aoyama3, Tsuyoshi Aoyama4, Barbara A. Ambrose9, Neil W. Ashton10, Michael J. Axtell7, Elizabeth I. Barker10, Michael S. Barker11, Jeffrey L. Bennetzen12, Nicholas D. Bonawitz1, Clint Chapple1, Chaoyang Cheng, Luiz Gustavo Guedes Corrêa13, Michael Dacre14, Jeremy D. DeBarry12, Ingo Dreyer13, Marek Eliáš15, Eric M. Engstrom16, Mark Estelle17, Liang Feng12, Cédric Finet18, Sandra K. Floyd5, Wolf B. Frommer19, Tomomichi Fujita20, Lydia Gramzow21, Michael Gutensohn1, Michael Gutensohn22, Jesper Harholt23, Mitsuru Hattori24, Mitsuru Hattori25, Alexander Heyl26, Tadayoshi Hirai27, Yuji Hiwatashi3, Yuji Hiwatashi4, Masaki Ishikawa, Mineko Iwata, Kenneth G. Karol9, Barbara Koehler13, Uener Kolukisaoglu28, Uener Kolukisaoglu29, Minoru Kubo, Tetsuya Kurata30, Sylvie Lalonde19, Kejie Li1, Ying Li31, Ying Li1, Amy Litt9, Eric Lyons32, Gerard Manning14, Takeshi Maruyama20, Todd P. Michael33, Koji Mikami20, Saori Miyazaki34, Saori Miyazaki3, Shin-Ichi Morinaga24, Shin-Ichi Morinaga3, TakashiMurata4, TakashiMurata3, Bernd Mueller-Roeber35, David R. Nelson36, Mari Obara, Yasuko Oguri, Richard G. Olmstead37, Naoko T. Onodera38, Bent O. Petersen23, Birgit Pils39, Michael J. Prigge17, Stefan A. Rensing40, Diego Mauricio Riaño-Pachón35, Diego Mauricio Riaño-Pachón41, Alison W. Roberts42, Yoshikatsu Sato, Henrik Vibe Scheller43, Henrik Vibe Scheller32, Burkhard Schulz1, Christian Schulz44, Eugene V. Shakirov45, Nakako Shibagaki46, Naoki Shinohara20, Dorothy E. Shippen45, Iben Sørensen47, Iben Sørensen23, Ryo Sotooka20, Nagisa Sugimoto, Mamoru Sugita25, Naomi Sumikawa3, Milos Tanurdzic48, Günter Theißen21, Peter Ulvskov23, Sachiko Wakazuki, Jing-Ke Weng14, Jing-Ke Weng1, William G.T. Willats23, Daniel Wipf49, Paul G. Wolf50, Lixing Yang12, Andreas Zimmer40, Qihui Zhu12, Therese Mitros32, Uffe Hellsten51, Dominique Loqué43, Robert Otillar51, Asaf Salamov51, Jeremy Schmutz51, Harris Shapiro51, Erika Lindquist51, Susan Lucas51, Daniel S. Rokhsar32, Daniel S. Rokhsar51, Igor V. Grigoriev51 
20 May 2011-Science
TL;DR: The genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported, is reported, finding that the transition from a gametophytes- to a sporophyte-dominated life cycle required far fewer new genes than the Transition from a non Seed vascular to a flowering plant.
Abstract: Vascular plants appeared ~410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.

750 citations


Journal ArticleDOI
TL;DR: The addition of oxaliplatin to capecitabine improves DFS in patients with stage III colon cancer, and XELOX is an additional adjuvant treatment option for these patients.
Abstract: Purpose This multicenter, randomized trial compared capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil (FU) and folinic acid (FA) as adjuvant therapy for patients with stage III colon cancer. Patients and Methods Patients who had undergone curative resection were randomly assigned to XELOX (oxaliplatin 130 mg/m 2 on day 1 plus capecitabine 1,000 mg/m 2 twice daily on days 1 to 14 every 3 weeks for 24 weeks) or a standard bolus FU/FA adjuvant regimen (Mayo Clinic for 24 weeks or Roswell Park for 32 weeks). The primary study end point was disease-free survival (DFS). Results The intention-to-treat population comprised 1,886 patients; 944 patients were randomly assigned to XELOX and 942 to FU/FA (Mayo Clinic, n 664; Roswell Park, n 278). After 57 months of follow-up for the primary analysis, 295 patients (31.3%) in the XELOX group had relapsed, developed a new primary colon cancer, or died compared with 353 patients (37.5%) in the FU/FA group (hazard ratio [HR] for DFS, 0.80; 95% CI, 0.69 to 0.93; P .0045). The 3-year DFS rate was 70.9% with XELOX and 66.5% with FU/FA. The HR for overall survival (OS) for XELOX compared to FU/FA was 0.87 (95% CI, 0.72 to 1.05; P .1486). The 5-year OS for XELOX and FU/FA were 77.6% and 74.2%, respectively. Follow-up is ongoing. Preplanned multivariate and subgroup analyses supported the robustness of these findings. Conclusion The addition of oxaliplatin to capecitabine improves DFS in patients with stage III colon cancer. XELOX is an additional adjuvant treatment option for these patients. J Clin Oncol 29. © 2011 by American Society of Clinical Oncology

643 citations


Proceedings ArticleDOI
30 Jun 2011
TL;DR: The Functional Mockup Interface (FMI) as discussed by the authors is a tool independent standard for the exchange of dynamic models and for co-simulation, which was developed by Daimler AG within the ITEA2 project MODELISAR.
Abstract: The Functional Mockup Interface (FMI) is a tool independent standard for the exchange of dynamic models and for co-simulation. The development of FMI was initiated and organized by Daimler AG within the ITEA2 project MODELISAR. The primary goal is to support the exchange of simulation models between suppliers and OEMs even if a large variety of different tools are used. The FMI was developed in a close collaboration between simulation tool vendors and research institutes. In this article an overview about FMI is given and technical details about the solution are discussed.

528 citations


Journal ArticleDOI
TL;DR: Soluble guanylate cyclase (sGC), a key enzyme of the nitric oxide (NO) signaling pathway, is attracting rapidly growing interest as a therapeutic target in cardiopulmonary disease, with several sGC agonists currently in clinical development.
Abstract: Soluble guanylate cyclase (sGC), a key enzyme of the nitric oxide (NO) signaling pathway, is attracting rapidly growing interest as a therapeutic target in cardiopulmonary disease, with several sGC agonists currently in clinical development. On binding of NO to a prosthetic heme group on sGC, the enzyme catalyzes synthesis of the second messenger cGMP, which produces vasorelaxation and inhibits smooth muscle proliferation, leukocyte recruitment, and platelet aggregation through a number of downstream mechanisms.1,2 Impaired NO and cGMP signaling has been implicated in the pathogenesis of cardiovascular disease, including systemic arterial and pulmonary hypertension (PH), coronary artery disease, peripheral vascular disease (including erectile dysfunction), and atherosclerosis.1,3,–,5 Organic nitrates that target the NO signaling pathway have been used to treat cardiovascular disease for >150 years. More recently, gaseous NO administered by inhalation has been approved for the treatment of persistent PH of the newborn.3,6 These agents nonetheless have several important limitations. Cardiovascular disease is associated with resistance to NO and organic nitrates.7 This may be due to the oxidative stress–induced alteration of the redox state of the prosthetic heme on sGC (from ferrous to ferric) that weakens the binding of heme to the enzyme and renders sGC unresponsive to NO.1,8 Furthermore, the long-term efficacy of organic nitrates is limited by the development of tolerance.9 Nitric oxide may also have numerous cytotoxic effects, mostly attributed to the reactive oxidant peroxynitrite (formed from the diffusion-controlled reaction of NO with superoxide).3,10 Peroxynitrite interacts with proteins and lipids, altering cellular signaling, disrupting mitochondrial function, and damaging DNA, which can eventually culminate in cellular dysfunction and/or death.3 Because the beneficial effects of NO appear to be …

508 citations


Journal ArticleDOI
TL;DR: Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.
Abstract: OBJECTIVE This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12). RESULTS TRT reduced HOMA-IR in the overall population by 15.2% at 6 months ( P = 0.018) and 16.4% at 12 months ( P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA 1c : treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate. CONCLUSIONS Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.

484 citations


Journal ArticleDOI
TL;DR: For the development of commercial biochar projects, reliable data on biochar production technologies is needed as mentioned in this paper, and a wide range of data on the costs of char production (between 51 US$ per tonne pyrolysis biochar from yard waste and 386 US$per tonne retort charcoal) and on the GHG balance of biochar systems are published.
Abstract: For the development of commercial biochar projects, reliable data on biochar production technologies is needed. For this purpose, peer-reviewed scientific articles on carbonization technologies (pyrolysis, gasification, hydrothermal carbonization, and flash carbonization) have been analyzed. Valuable information is provided by papers on pyrolysis processes, less information is available on gasification processes, and few papers about hydrothermal and flash carbonization technologies were identified. A wide range of data on the costs of char production (between 51 US$ per tonne pyrolysis biochar from yard waste and 386 US$ per tonne retort charcoal) and on the GHG balance of biochar systems (between −1054 kg CO2e and +123 kg CO2e per t dry biomass feedstock) have been published. More data from pilot projects are needed to improve the evaluation of biochar production technologies. Additional research on the influence of biochar application on surface albedo, atmospheric soot concentration, and yield respons...

478 citations


Journal ArticleDOI
Abbas Dehghan1, Josée Dupuis2, Josée Dupuis3, Maja Barbalić4, Joshua C. Bis5, Gudny Eiriksdottir, Chen Lu2, Niina Pellikka, Henri Wallaschofski6, Johannes Kettunen7, Peter Henneman8, Jens Baumert, David P. Strachan9, Christian Fuchsberger, Veronique Vitart10, James F. Wilson10, Guillaume Paré11, Silvia Naitza, Megan E. Rudock12, Ida Surakka13, Eco J. C. de Geus14, Behrooz Z. Alizadeh, Jack M. Guralnik3, Alan R. Shuldiner, Toshiko Tanaka, Robert Y.L. Zee11, Renate B. Schnabel15, Vijay Nambi16, Maryam Kavousi1, Samuli Ripatti13, Matthias Nauck6, Nicholas L. Smith5, Albert V. Smith, Jouko Sundvall, Paul Scheet17, Yongmei Liu12, Aimo Ruokonen18, Lynda M. Rose11, Martin G. Larson2, Martin G. Larson3, Ron C. Hoogeveen16, Nelson B. Freimer11, Alexander Teumer, Russell P. Tracy, Lenore J. Launer3, Julie E. Buring11, Jennifer F. Yamamoto3, Jennifer F. Yamamoto2, Aaron R. Folsom19, Eric J.G. Sijbrands1, James S. Pankow19, Paul Elliott20, John F. Keaney2, John F. Keaney3, Wei Sun21, Antti-Pekka Sarin13, João D. Fontes3, João D. Fontes2, Sunita Badola, Brad C. Astor16, Albert Hofman1, Anneli Pouta, Karl Werdan22, Karin Halina Greiser22, Karin Halina Greiser23, Oliver Kuss22, Henriette E. Meyer zu Schwabedissen, Joachim Thiery24, Yalda Jamshidi9, Yalda Jamshidi25, Ilja M. Nolte, Nicole Soranzo7, Tim D. Spector9, Henry Völzke, Alex Parker26, Thor Aspelund27, David W. Bates11, Lauren Young26, Kim Tsui26, David S. Siscovick5, Xiuqing Guo28, Jerome I. Rotter28, Manuela Uda, David Schlessinger, Igor Rudan10, Igor Rudan29, Andrew A. Hicks, Brenda W.J.H. Penninx14, Barbara Thorand, Christian Gieger, Joe Coresh16, Gonneke Willemsen14, Tamara B. Harris3, André G. Uitterlinden1, Marjo-Riitta Järvelin, Kenneth Rice5, Dörte Radke, Veikko Salomaa, Ko Willems van Dijk8, Eric Boerwinkle4, Ramachandran S. Vasan, Luigi Ferrucci, Quince Gibson, Stefania Bandinelli, Harold Snieder, Dorret I. Boomsma14, Xiangjun Xiao17, Harry Campbell10, Caroline Hayward10, Peter P. Pramstaller, Cornelia M. van Duijn1, Leena Peltonen7, Bruce M. Psaty, Vilmundur Gudnason27, Paul M. Ridker11, Georg Homuth, Wolfgang Koenig30, Christie M. Ballantyne16, Jacqueline C.M. Witteman1, Emelia J. Benjamin, Markus Perola, Daniel I. Chasman11 
TL;DR: A genome-wide association analysis of CRP identified 18 loci that were associated with CRP levels and highlighted immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.
Abstract: Background—C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels. Methods and Results—We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2) or the immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1) or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found a significant interaction of body ...

463 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated leaching of dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), and dissolved methane (CH4), at forests, grasslands, and croplands across Europe.
Abstract: Estimates of carbon leaching losses from different land use systems are few and their contribution to the net ecosystem carbon balance is uncertain. We investigated leaching of dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), and dissolved methane (CH4), at forests, grasslands, and croplands across Europe. Biogenic contributions to DIC were estimated by means of its δ13C signature. Leaching of biogenic DIC was 8.3±4.9 g m−2 yr−1 for forests, 24.1±7.2 g m−2 yr−1 for grasslands, and 14.6±4.8 g m−2 yr−1 for croplands. DOC leaching equalled 3.5±1.3 g m−2 yr−1 for forests, 5.3±2.0 g m−2 yr−1 for grasslands, and 4.1±1.3 g m−2 yr−1 for croplands. The average flux of total biogenic carbon across land use systems was 19.4±4.0 g C m−2 yr−1. Production of DOC in topsoils was positively related to their C/N ratio and DOC retention in subsoils was inversely related to the ratio of organic carbon to iron plus aluminium (hydr)oxides. Partial pressures of CO2 in soil air and soil pH determined DIC concentrations and fluxes, but soil solutions were often supersaturated with DIC relative to soil air CO2. Leaching losses of biogenic carbon (DOC plus biogenic DIC) from grasslands equalled 5–98% (median: 22%) of net ecosystem exchange (NEE) plus carbon inputs with fertilization minus carbon removal with harvest. Carbon leaching increased the net losses from cropland soils by 24–105% (median: 25%). For the majority of forest sites, leaching hardly affected actual net ecosystem carbon balances because of the small solubility of CO2 in acidic forest soil solutions and large NEE. Leaching of CH4 proved to be insignificant compared with other fluxes of carbon. Overall, our results show that leaching losses are particularly important for the carbon balance of agricultural systems.

392 citations


Journal ArticleDOI
TL;DR: In this article, the authors compared eleven different indicators for quantifying surface urban heat islands that were most frequently used in recent publications on remote sensing-based urban heat island assessments and found that the indicators individually reveal diurnal and seasonal patterns but show rather low correlations over time, and for single points in time, the different indicators show only weak correlations.

347 citations


Journal ArticleDOI
TL;DR: In this article, a large dataset was collected to form base to repeated soil inventories at 12 CarboEurope sites under different climate and land-use, and with different soil types, where concentrations of organic carbon, bulk density, and fine earth fraction were determined to 60 cm depth at 100 sampling points per site.
Abstract: . Precise determination of changes in organic carbon (OC) stocks is prerequisite to understand the role of soils in the global cycling of carbon and to verify changes in stocks due to management. A large dataset was collected to form base to repeated soil inventories at 12 CarboEurope sites under different climate and land-use, and with different soil types. Concentration of OC, bulk density (BD), and fine earth fraction were determined to 60 cm depth at 100 sampling points per site. We investigated (1) time needed to detect changes in soil OC, assuming future re-sampling of 100 cores; (2) the contribution of different sources of uncertainties to OC stocks; (3) the effect of OC stock calculation on mass rather than volume base for change detection; and (4) the potential use of pedotransfer functions (PTF) for estimating BD in repeated inventories. The period of time needed for soil OC stocks to change strongly enough to be detectable depends on the spatial variability of soil properties, the depth increment considered, and the rate of change. Cropland sites, having small spatial variability, had lower minimum detectable differences (MDD) with 100 sampling points (105 p 28 gC m−2 for the upper 10 cm of the soil) than grassland and forest sites (206 p 64 and 246 p 64 gC m−2 for 0–10 cm, respectively). Expected general trends in soil OC indicate that changes could be detectable after 2–15 yr with 100 samples if changes occurred in the upper 10 cm of stone-poor soils. Error propagation analyses showed that in undisturbed soils with low stone contents, OC concentrations contributed most to OC stock variability while BD and fine earth fraction were more important in upper soil layers of croplands and in stone rich soils. Though the calculation of OC stocks based on equivalent soil masses slightly decreases the chance to detect changes with time at most sites except for the croplands, it is still recommended to account for changing bulk densities with time. Application of PTF for the estimation of bulk densities caused considerable underestimation of total variances of OC stocks if the error associated with the PTF was not accounted for, which rarely is done in soil inventories. Direct measurement of all relevant parameters approximately every 10 yr is recommended for repeated soil OC inventories.

Journal ArticleDOI
TL;DR: In this review, advances in understanding mechanisms of biotrophy, necrotrophy and hemibiotrophic lifestyles are described and special emphasis is given to biosynthesis, chemical diversity and mode of action of various fungal toxins produced during the infection process.

Journal ArticleDOI
TL;DR: The Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy and concluded that rodent data can well be used as a basis for human risk evaluation and conjectures that rats are insensitive to estrogens compared to humans can be refuted.
Abstract: Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure...

Journal ArticleDOI
TL;DR: HTPheno, an open source image analysis pipeline, supplies a flexible and adaptable ImageJ plugin which can be used for automated image analysis in high-throughput plant phenotyping and therefore to derive new biological insights, such as determination of fitness.
Abstract: In the last few years high-throughput analysis methods have become state-of-the-art in the life sciences. One of the latest developments is automated greenhouse systems for high-throughput plant phenotyping. Such systems allow the non-destructive screening of plants over a period of time by means of image acquisition techniques. During such screening different images of each plant are recorded and must be analysed by applying sophisticated image analysis algorithms. This paper presents an image analysis pipeline (HTPheno) for high-throughput plant phenotyping. HTPheno is implemented as a plugin for ImageJ, an open source image processing software. It provides the possibility to analyse colour images of plants which are taken in two different views (top view and side view) during a screening. Within the analysis different phenotypical parameters for each plant such as height, width and projected shoot area of the plants are calculated for the duration of the screening. HTPheno is applied to analyse two barley cultivars. HTPheno, an open source image analysis pipeline, supplies a flexible and adaptable ImageJ plugin which can be used for automated image analysis in high-throughput plant phenotyping and therefore to derive new biological insights, such as determination of fitness.

Journal ArticleDOI
15 Aug 2011-Entropy
TL;DR: It is shown that minimum entropy production can be obtained when the thermoelectric potential is a specific, optimal value, and based on a historical overview, the compatibility approach together with the thermodynamic arguments is reconsidered.
Abstract: Fifty years ago, the optimization of thermoelectric devices was analyzed by considering the relation between optimal performances and local entropy production. Entropy is produced by the irreversible processes in thermoelectric devices. If these processes could be eliminated, entropy production would be reduced to zero, and the limiting Carnot efficiency or coefficient of performance would be obtained. In the present review, we start with some fundamental thermodynamic considerations relevant for thermoelectrics. Based on a historical overview, we reconsider the interrelation between optimal performances and local entropy production by using the compatibility approach together with the thermodynamic arguments. Using the relative current density and the thermoelectric potential, we show that minimum entropy production can be obtained when the thermoelectric potential is a specific, optimal value.

Journal ArticleDOI
TL;DR: The persistence or disappearance of antibodies to MOG may have prognostic relevance for acute childhood demyelination in patients diagnosed with childhood MS.
Abstract: Objective: To study the longitudinal dynamics of anti–myelin oligodendrocyte glycoprotein (MOG) autoantibodies in childhood demyelinating diseases. Methods: We addressed the kinetics of anti-MOG immunoglobulins in a prospective study comprising 77 pediatric patients. This was supplemented by a cross-sectional study analyzing 126 pediatric patients with acute demyelination and 62 adult patients with multiple sclerosis (MS). MOG-transfected cells were used for detection of antibodies by flow cytometry. Results: Twenty-five children who were anti-MOG immunoglobulin (Ig) positive at disease onset were followed for up to 5 years. Anti-MOG antibodies rapidly and continuously declined in all 16 monophasic patients with acute disseminated encephalomyelitis and in one patient with clinically isolated syndrome. In contrast, in 6 of 8 patients (75%) eventually diagnosed with childhood MS, the antibodies to MOG persisted with fluctuations showing a second increase during an observation period of up to 5 years. Antibodies to MOG were mainly IgG 1 and their binding was largely blocked by pathogenic anti-MOG antibodies derived from a spontaneous animal model of autoimmune encephalitis. The cross-sectional part of our study elaborated that anti-MOG Ig was present in about 25% of children with acute demyelination, but in none of the pediatric or adult controls. Sera from 4/62 (6%) adult patients with MS had anti-MOG IgG at low levels. Conclusions: The persistence or disappearance of antibodies to MOG may have prognostic relevance for acute childhood demyelination.

Journal ArticleDOI
TL;DR: A cloning approach that facilitates the assembly of multiple repeat-encoding DNA fragments that translate into dTALEs with pre-defined DNA binding specificity that allow rapid generation of highly specific TALE-type DNA binding domains that target binding sites of predefined length and sequence is presented.
Abstract: Transcription activator-like effector (TALE) DNA binding proteins show tremendous potential as molecular tools for targeted binding to any desired DNA sequence. Their DNA binding domain consists of tandem arranged repeats, and due to this repetitive structure it is challenging to generate designer TALEs (dTALEs) with user-defined specificity. We present a cloning approach that facilitates the assembly of multiple repeat-encoding DNA fragments that translate into dTALEs with pre-defined DNA binding specificity. This method makes use of type IIS restriction enzymes in two sequential cut-ligase reactions to build dTALE repeat arrays. We employed this modular approach for generation of a dTALE that differentiates between two highly similar DNA sequences that are both targeted by the Xanthomonas TALE, AvrBs3. These data show that this modular assembly system allows rapid generation of highly specific TALE-type DNA binding domains that target binding sites of predefined length and sequence. This approach enables the rapid and flexible production of dTALEs for gene regulation and genome editing in routine and high-throughput applications.

Journal ArticleDOI
TL;DR: In this paper, the effects of climate or weather extremes such as drought and heat waves on biodiversity and ecosystem functions are studied in a single study in order to address general patterns across different categories of responses and to analyse effects of weather extremes on various ecosystem functions.
Abstract: Summary 1. Studying the effects of climate or weather extremes such as drought and heat waves on biodiversity and ecosystem functions is one of the most important facets of climate change research. In particular, primary production is amounting to the common currency in field experiments world-wide. Rarely, however, are multiple ecosystem functions measured in a single study in order to address general patterns across different categories of responses and to analyse effects of climate extremes on various ecosystem functions. 2. We set up a long-term field experiment, where we applied recurrent severe drought events annually for five consecutive years to constructed grassland communities in central Europe. The 32 response parameters studied were closely related to ecosystem functions such as primary production, nutrient cycling, carbon fixation, water regulation and community stability. 3. Surprisingly, in the face of severe drought, above- and below-ground primary production of plants remained stable across all years of the drought manipulation. 4. Yet, severe drought significantly reduced below-ground performance of microbes in soil indicated by reduced soil respiration, microbial biomass and cellulose decomposition rates as well as mycorrhization rates. Furthermore, drought reduced leaf water potential, leaf gas exchange and leaf protein content, while increasing maximum uptake capacity, leaf carbon isotope signature and leaf carbohydrate content. With regard to community stability, drought induced complementary plant–plant interactions and shifts in flower phenology, and decreased invasibility of plant communities and primary consumer abundance. 5. Synthesis. Our results provide the first field-based experimental evidence that climate extremes initiate plant physiological processes, which may serve to regulate ecosystem productivity. A potential reason for different dynamics in various ecosystem services facing extreme climatic events may lie in the temporal hierarchy of patterns of fast versus slow response. Such data on multiple response parameters within climate change experiments foster the understanding of mechanisms of resilience, of synergisms or decoupling of biogeochemical processes, and of fundamental response dynamics to drought at the ecosystem level including potential tipping points and thresholds of regime shift. Future work is needed to elucidate the role of biodiversity and of biotic interactions in modulating ecosystem response to climate extremes.

Journal ArticleDOI
TL;DR: This review gives a short overview over the instrumentation used in cryo-TEM experiments and over the sample preparation procedure.

Journal ArticleDOI
TL;DR: This study provides a global view of the evolution of LESS in the field of minimally invasive urologic surgery and shows that a broad range of procedures have been effectively performed, primarily in the academic setting, within diverse health care systems around the world.

Journal ArticleDOI
TL;DR: A largely ignored role of these organisms in attenuating pollutant loads in freshwaters and their potential use in environmental biotechnology is suggested.
Abstract: Research on freshwater fungi has concentrated on their role in plant litter decomposition in streams. Higher fungi dominate over bacteria in terms of biomass, production and enzymatic substrate degradation. Microscopy-based studies suggest the prevalence of aquatic hyphomycetes, characterized by tetraradiate or sigmoid spores. Molecular studies have consistently demonstrated the presence of other fungal groups, whose contributions to decomposition are largely unknown. Molecular methods will allow quantification of these and other microorganisms. The ability of aquatic hyphomycetes to withstand or mitigate anthropogenic stresses is becoming increasingly important. Metal avoidance and tolerance in freshwater fungi implicate a sophisticated network of mechanisms involving external and intracellular detoxification. Examining adaptive responses under metal stress will unravel the dynamics of biochemical processes and their ecological consequences. Freshwater fungi can metabolize organic xenobiotics. For many such compounds, terrestrial fungal activity is characterized by cometabolic biotransformations involving initial attack by intracellular and extracellular oxidative enzymes, further metabolization of the primary oxidation products via conjugate formation and a considerable versatility as to the range of metabolized pollutants. The same capabilities occur in freshwater fungi. This suggests a largely ignored role of these organisms in attenuating pollutant loads in freshwaters and their potential use in environmental biotechnology.

Journal ArticleDOI
TL;DR: The mechanism of length control during nuclear processing of pre‐mRNAs is relatively well understood and is based on the changes in the processivity of poly(A) polymerase induced by two RNA‐binding proteins.
Abstract: Poly(A) tails have long been known as stable 3' modifications of eukaryotic mRNAs, added during nuclear pre-mRNA processing. It is now appreciated that this modification is much more diverse: A whole new family of poly(A) polymerases has been discovered, and poly(A) tails occur as transient destabilizing additions to a wide range of different RNA substrates. We review the field from the perspective of poly(A) tail length. Length control is important because (1) poly(A) tail shortening from a defined starting point acts as a timer of mRNA stability, (2) changes in poly(A) tail length are used for the purpose of translational regulation, and (3) length may be the key feature distinguishing between the stabilizing poly(A) tails of mRNAs and the destabilizing oligo(A) tails of different unstable RNAs. The mechanism of length control during nuclear processing of pre-mRNAs is relatively well understood and is based on the changes in the processivity of poly(A) polymerase induced by two RNA-binding proteins. Developmentally regulated poly(A) tail extension also generates defined tails; however, although many of the proteins responsible are known, the reaction is not understood mechanistically. Finally, destabilizing oligoadenylation does not appear to have inherent length control. Rather, average tail length results from the balance between polyadenylation and deadenylation.

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TL;DR: A novel and computationally efficient method to design optimal control places, and an iteration approach that only computes the reachability graph of a plant Petri net model once in order to obtain a maximally permissive liveness-enforcing supervisor for an FMS.
Abstract: Deadlock prevention plays an important role in the modeling and control of flexible manufacturing systems (FMS). This paper presents a novel and computationally efficient method to design optimal control places, and an iteration approach that only computes the reachability graph of a plant Petri net model once in order to obtain a maximally permissive liveness-enforcing supervisor for an FMS. By using a vector covering approach, a minimal covering set of legal markings and a minimal covered set of first-met bad markings (FBM) are computed. At each iteration, an FBM from the minimal covered set is selected. By solving an integer linear programming problem, a place invariant is designed to prevent the FBM from being reached and no marking in the minimal covering set of legal markings is forbidden. This process is carried out until no FBM can be reached. In order to make the considered problem computationally tractable, binary decision diagrams (BDD) are used to compute the sets of legal markings and FBM, and solve the vector covering problem to get a minimal covering set of legal markings and a minimal covered set of FBM. Finally, a number of FMS examples are presented to illustrate the proposed approaches.

Journal ArticleDOI
TL;DR: The PP-LFERs revealed that partition coefficients into membrane lipids can be two log units higher than those into storage lipids for H-bond donor compounds, suggesting that distinguishing between the two lipids is necessary to account for the bioaccumulation of these compounds.
Abstract: Lipids have been considered as the predominant components for bioaccumulation of organic chemicals. However, differences in accumulation properties between different types of lipid (e.g., storage and membrane lipids) have rarely been considered. Moreover, in view of toxic effects on organisms, chemical accumulation specifically in biological membranes is of particular importance. In this review article, partition coefficients of 240 neutral organic compounds between liposomes (phospholipid membrane vesicles) and water (Klipw), reported in the literature or measured additionally for this work, were evaluated. Values of log Klipw and log Kow (octanol–water partition coefficients) differ by 0.4 on average. Polyparameter linear free energy relationships (PP-LFERs) can describe the log Klipw data even better (standard deviations = 0.28–0.31) than the log Kow model. Recent experimental data for highly hydrophobic compounds fit well to the PP-LFERs and do not indicate the existence of a previously postulated “hy...

Journal ArticleDOI
19 May 2011-PLOS ONE
TL;DR: Synthetic TAL proteins with designed repeat compositions were created using a novel modular cloning strategy termed “Golden TAL Technology” and activated targeted expression of exogenous as well as endogenous genes.
Abstract: TAL (transcription activator-like) effectors are translocated by Xanthomonas bacteria into plant cells where they activate transcription of target genes. DNA target sequence recognition occurs in a unique mode involving a central domain of tandem repeats. Each repeat recognizes a single base pair in a contiguous DNA sequence and a pair of adjacent hypervariable amino acid residues per repeat specifies which base is bound. Rearranging the repeats allows the design of novel TAL proteins with predictable DNA-recognition specificities. TAL protein-based transcriptional activation in plant cells is mediated by a C-terminal activation domain (AD). Here, we created synthetic TAL proteins with designed repeat compositions using a novel modular cloning strategy termed “Golden TAL Technology”. Newly programmed TAL proteins were not only functional in plant cells, but also in human cells and activated targeted expression of exogenous as well as endogenous genes. Transcriptional activation in different human cell lines was markedly improved by replacing the TAL-AD with the VP16-AD of herpes simplex virus. The creation of TAL proteins with potentially any desired DNA-recognition specificity allows their versatile use in biotechnology.

Journal ArticleDOI
01 May 2011-Ecology
TL;DR: The results challenge the traditional view regarding the fate and role of lignin during litter decomposition and suggest that bioavailable, soluble compounds became a limiting factor for CO2 production.
Abstract: Lignin is a main component of plant litter. Its degradation is thought to be critical for litter decomposition rates and the build-up of soil organic matter. We studied the relationships between lignin degradation and the production of dissolved organic carbon (DOC) and of CO2 during litter decomposition. Needle or leaf litter of five species (Norway spruce, Scots pine, mountain ash, European beech, sycamore maple) and of different decomposition stage (freshly fallen and up to 27 months of field exposure) was incubated in the laboratory for two years. Lignin degradation was followed with the CuO method. Strong lignin degradation occurred during the first 200 incubation days, as revealed by decreasing yields of lignin-derived phenols. Thereafter lignin degradation leveled off. This pattern was similar for fresh and decomposed litter, and it stands in contrast to the common view of limited lignin degradation in fresh litter. Dissolved organic carbon and CO2 also peaked in the first period of the incubation but were not interrelated. In the later phase of incubation, CO2 production was positively correlated with DOC amounts, suggesting that bioavailable, soluble compounds became a limiting factor for CO2 production. Lignin degradation occurred only when CO2 production was high, and not limited by bioavailable carbon. Thus carbon availability was the most important control on lignin degradation. In turn, lignin degradation could not explain differences in DOC and CO2 production over the study period. Our results challenge the traditional view regarding the fate and role of lignin during litter decomposition. Lignin degradation is controlled by the availability of easily decomposable carbon sources. Consequently, it occurs particularly in the initial phase of litter decomposition and is hampered at later stages if easily decomposable resources decline.

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TL;DR: New tools for site-specific genome targeting in human cells are generated from TALE proteins, paving the way for new approaches to personalized medicine.
Abstract: New tools for site-specific genome targeting in human cells are generated from TALE proteins.

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TL;DR: It is found that Jacob, a messenger that can couple extrasynaptic NMDA-receptor activity to CREB dephosphorylation, accumulates in the nucleus after Aβ oligomer administration and that the nuclear accumulation of Jacob can be blocked by a simultaneous application of ifenprodil.

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TL;DR: Subtropical broad-leaved forests in southeastern China support a high diversity of woody plants, and a number of environmen...
Abstract: Subtropical broad-leaved forests in southeastern China support a high diversity of woody plants. Using a comparative study design with 30 × 30 m plots (n = 27) from five successional stages ( 1 m in height in each plot and counted all woody recruits (bank of all seedlings ≤1 m in height) in each central 10 × 10 m quadrant of each plot. In addition, we measured a number of environmen...

Journal ArticleDOI
TL;DR: In this paper, the dynamics of the polymer matrix in filled rubbers is modified by the presence of solid particles, and the authors used low-field proton NMR to investigate model filled samples consisting of a dispersion of g...
Abstract: The dynamics of the polymer matrix in filled rubbers is modified by the presence of solid particles. We used low-field proton NMR to investigate model filled samples consisting of a dispersion of g...