Showing papers by "University of Freiburg published in 2009"
University of Ottawa1, Mario Negri Institute for Pharmacological Research2, University of Modena and Reggio Emilia3, Ottawa Hospital Research Institute4, University of Oxford5, University of Freiburg6, Veterans Health Administration7, Johnson & Johnson8, Johnson & Johnson Pharmaceutical Research and Development9, University of Birmingham10, McMaster University11, Johns Hopkins University12, University of Bern13, University of Copenhagen14, Medical Research Council15, GlaxoSmithKline16, University of California, San Francisco17, FHI 36018, Cochrane Collaboration19
TL;DR: Provide a structured summary including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings, systematic review registration number 2.
Abstract: Provide a structured summary including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings, systematic review registration number 2 Structured summary
3,655 citations
Cardiff University1, Medical Research Council2, University of Bristol3, National Institute for Health Research4, King's College5, Trinity College, Dublin6, University of Cambridge7, University of Nottingham8, Queen's University Belfast9, University of Southampton10, University of Manchester11, John Radcliffe Hospital12, UCL Institute of Neurology13, University of Bonn14, University of Hamburg15, Charité16, University of Erlangen-Nuremberg17, University of Duisburg-Essen18, Ludwig Maximilian University of Munich19, Heidelberg University20, University College Dublin21, University of Freiburg22, Washington University in St. Louis23, Brigham Young University24, University of Antwerp25, University College London26, Wellcome Trust Sanger Institute27, King's College London28, Aristotle University of Thessaloniki29, National Institutes of Health30, Mayo Clinic31
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Abstract: We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).
2,956 citations
University of Paris-Sud1, Institut Gustave Roussy2, French Institute of Health and Medical Research3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, Boston Children's Hospital11, University of Gothenburg12, University of Freiburg13, University of California, San Francisco14, Buck Institute for Research on Aging15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Howard Hughes Medical Institute25, Yale University26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, University of Göttingen45, Stony Brook University46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells
2,218 citations
TL;DR: It is proposed that ZEB1 links EMT-activation and stemness-maintenance by suppressingstemness-inhibiting microRNAs (miRNAs) and thereby is a promoter of mobile, migrating cancer stem cells.
Abstract: Invasion and metastasis of carcinomas is promoted by the activation of the embryonic 'epithelial to mesenchymal transition' (EMT) program, which triggers cellular mobility and subsequent dissemination of tumour cells. We recently showed that the EMT-activator ZEB1 (zinc finger E-box binding homeobox 1) is a crucial promoter of metastasis and demonstrated that ZEB1 inhibits expression of the microRNA-200 (miR-200) family, whose members are strong inducers of epithelial differentiation. Here, we report that ZEB1 not only promotes tumour cell dissemination, but is also necessary for the tumour-initiating capacity of pancreatic and colorectal cancer cells. We show that ZEB1 represses expression of stemness-inhibiting miR-203 and that candidate targets of miR-200 family members are also stem cell factors, such as Sox2 and Klf4. Moreover, miR-200c, miR-203 and miR-183 cooperate to suppress expression of stem cell factors in cancer cells and mouse embryonic stem (ES) cells, as demonstrated for the polycomb repressor Bmi1. We propose that ZEB1 links EMT-activation and stemness-maintenance by suppressing stemness-inhibiting microRNAs (miRNAs) and thereby is a promoter of mobile, migrating cancer stem cells. Thus, targeting the ZEB1-miR-200 feedback loop might form the basis of a promising treatment for fatal tumours, such as pancreatic cancer.
1,622 citations
TL;DR: Recent insights into the importing and sorting of mitochondrial proteins and their contributions to mitochondrial biogenesis are discussed.
1,271 citations
TL;DR: Findings support the existence of a consolidation mechanism, susceptible to anodal tDCS, which contributes to offline effects but not to online effects or long-term retention, and may hold promise for the rehabilitation of brain injury.
Abstract: Motor skills can take weeks to months to acquire and can diminish over time in the absence of continued practice. Thus, strategies that enhance skill acquisition or retention are of great scientific and practical interest. Here we investigated the effect of noninvasive cortical stimulation on the extended time course of learning a novel and challenging motor skill task. A skill measure was chosen to reflect shifts in the task's speed–accuracy tradeoff function (SAF), which prevented us from falsely interpreting variations in position along an unchanged SAF as a change in skill. Subjects practiced over 5 consecutive days while receiving transcranial direct current stimulation (tDCS) over the primary motor cortex (M1). Using the skill measure, we assessed the impact of anodal (relative to sham) tDCS on both within-day (online) and between-day (offline) effects and on the rate of forgetting during a 3-month follow-up (long-term retention). There was greater total (online plus offline) skill acquisition with anodal tDCS compared to sham, which was mediated through a selective enhancement of offline effects. Anodal tDCS did not change the rate of forgetting relative to sham across the 3-month follow-up period, and consequently the skill measure remained greater with anodal tDCS at 3 months. This prolonged enhancement may hold promise for the rehabilitation of brain injury. Furthermore, these findings support the existence of a consolidation mechanism, susceptible to anodal tDCS, which contributes to offline effects but not to online effects or long-term retention.
1,239 citations
TL;DR: This work suggests an approach that exploits the profile likelihood that enables to detect structural non-identifiabilities, which manifest in functionally related model parameters, that might arise due to limited amount and quality of experimental data.
Abstract: Motivation: Mathematical description of biological reaction networks by differential equations leads to large models whose parameters are calibrated in order to optimally explain experimental data. Often only parts of the model can be observed directly. Given a model that sufficiently describes the measured data, it is important to infer how well model parameters are determined by the amount and quality of experimental data. This knowledge is essential for further investigation of model predictions. For this reason a major topic in modeling is identifiability analysis.
Results: We suggest an approach that exploits the profile likelihood. It enables to detect structural non-identifiabilities, which manifest in functionally related model parameters. Furthermore, practical non-identifiabilities are detected, that might arise due to limited amount and quality of experimental data. Last but not least confidence intervals can be derived. The results are easy to interpret and can be used for experimental planning and for model reduction.
Availability: An implementation is freely available for MATLAB and the PottersWheel modeling toolbox at http://web.me.com/andreas.raue/profile/software.html.
Contact: andreas.raue@me.com
Supplementary information:Supplementary data are available at Bioinformatics online.
1,150 citations
TL;DR: A general measure for the degree of non-Markovian behavior in open quantum systems is constructed based on the trace distance which quantifies the distinguishability of quantum states, which represents a functional of the dynamical map describing the time evolution of physical states.
Abstract: We construct a general measure for the degree of non-Markovian behavior in open quantum systems. This measure is based on the trace distance which quantifies the distinguishability of quantum states. It represents a functional of the dynamical map describing the time evolution of physical states, and can be interpreted in terms of the information flow between the open system and its environment. The measure takes on nonzero values whenever there is a flow of information from the environment back to the open system, which is the key feature of non-Markovian dynamics.
1,142 citations
TL;DR: In contrast to the conventional Pd/C catalyst, graphite oxide and graphene-based catalysts gave much higher activities with turnover frequencies exceeding 39,000 h(-1), accompanied by very low palladium leaching (<1 ppm).
Abstract: Pd2+-exchanged graphite oxide and chemically derived graphenes therefrom were employed as supports for Pd nanoparticles. The influence of catalyst preparation, carbon functionalization, and catalyst morphology on the catalytic activity in the Suzuki−Miyaura coupling reactions was investigated. The catalysts were characterized by means of spectroscopy (FT-IR, solid-state 13C NMR, AAS, XPS), X-ray scattering (WAXS), surface area analysis (BET, methylene blue adsorption), and electron microscopy (TEM, ESEM). In contrast to the conventional Pd/C catalyst, graphite oxide and graphene-based catalysts gave much higher activities with turnover frequencies exceeding 39 000 h−1, accompanied by very low palladium leaching (<1 ppm).
1,113 citations
TL;DR: Inorganic solid-state materials doped with rare-earth ions are very promising and are in the focus of current research activities for the development of economical light sources like white-light-emitting diodes and display panels with enhanced efficiency.
Abstract: Because fossil fuels are becoming scarce and because of the expected climate change, our standard of living can only be maintained by a significant increase in energy efficiency. Large amounts of energy are consumed for lighting and during operation of displays. Thus, the targets are the development of economical light sources like white-light-emitting diodes and display panels with enhanced efficiency. Solar energy is converted into electricity by solar cells, and their efficiency must be improved considerably. A possible contribution might be delivered by phosphors which allow the conversion of thermal radiation into electrical energy. Although the target of energy efficiency is very important, we must not overlook that medical imaging diagnostic methods require efficient and sensitive detectors. For the solution of these central questions, inorganic solid-state materials doped with rare-earth ions are very promising and are therefore in the focus of current research activities.
944 citations
TL;DR: This systematic analysis shows that microfracture provides effective short-term functional improvement of knee function but insufficient data are available on its long-term results.
Abstract: Background Despite the popularity of microfracture as a first-line treatment for articular cartilage defects in the knee, systematic information on its clinical efficacy for articular cartilage repair and long-term improvement of knee function is not available. Hypothesis Systematic analysis of the existing clinical literature of microfracture in the knee can improve the understanding of the advantages and limitations of this cartilage repair technique and can help to optimize its indications and clinical outcomes. Study design Systematic review. Methods A comprehensive literature search was performed using established search engines (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials) to identify original human studies of articular cartilage repair with microfracture. Modified Coleman Methodology Scores were used to analyze the quality of the existing studies. Clinical efficacy of articular cartilage repair was evaluated by systematic analysis of short- and long-term functional outcome scores, macroscopic and microscopic repair cartilage quality, and findings of postoperative magnetic resonance imaging. Results Twenty-eight studies describing 3122 patients were included in the review. The average follow-up was 41 months, with only 5 studies reporting follow-up of 5 years or more. Six studies were randomized controlled trials and the mean Coleman Methodology Score was 58 (range, 22-97). Microfracture effectively improved knee function in all studies during the first 24 months after microfracture, but the reports on durability of the initial functional improvement were conflicting. Several factors were identified that affected clinical outcome. Defect fill on magnetic resonance imaging was highly variable and correlated with functional outcome. Macroscopic repair cartilage quality positively affected long-term failure rate, while the influence of histologic repair tissue quality remained inconclusive. Conclusion This systematic analysis shows that microfracture provides effective short-term functional improvement of knee function but insufficient data are available on its long-term results. Shortcomings of the technique include limited hyaline repair tissue, variable repair cartilage volume, and possible functional deterioration. The quality of the currently available data on micro-fracture is still limited by the variability of results and study designs. Further well-designed studies are needed to determine the long-term efficacy of microfracture and to define its specific clinical indications compared to other cartilage repair techniques.
TL;DR: Evidence is provided that signals from the commensal microflora contribute to the differentiation of a lymphocyte population coexpressing stimulatory natural killer cell receptors and the transcription factor RORγt that produced interleukin 22 (IL-22).
Abstract: The mucosal immune system of the intestine is separated from a vast array of microbes by a single layer of epithelial cells. Cues from the commensal microflora are needed to maintain epithelial homeostasis, but the molecular and cellular identities of these cues are unclear. Here we provide evidence that signals from the commensal microflora contribute to the differentiation of a lymphocyte population coexpressing stimulatory natural killer cell receptors and the transcription factor RORgammat that produced interleukin 22 (IL-22). The emergence of these IL-22-producing RORgammathiNKp46+NK1.1(int) cells depended on RORgammat expression, which indicated that these cells may have been derived from lymphoid tissue-inducer cells. IL-22 released by these cells promoted the production of antimicrobial molecules important in the maintenance of mucosal homeostasis.
TL;DR: This normative analysis provides a heuristic framework for organizing past and future research on implicit measures and reviews past research on the 2 implicit measures that are currently most popular: effects in implicit association tests and affective priming tasks.
Abstract: Implicit measures can be defined as outcomes of measurement procedures that are caused in an automatic manner by psychological attributes. To establish that a measurement outcome is an implicit measure, one should examine (a) whether the outcome is causally produced by the psychological attribute it was designed to measure, (b) the nature of the processes by which the attribute causes the outcome, and (c) whether these processes operate automatically. This normative analysis provides a heuristic framework for organizing past and future research on implicit measures. The authors illustrate the heuristic function of their framework by using it to review past research on the 2 implicit measures that are currently most popular: effects in implicit association tests and affective priming tasks.
deCODE genetics1, University of Iceland2, University of Western Australia3, Sir Charles Gairdner Hospital4, University Medical Center Groningen5, University of Freiburg6, University of Groningen7, Queen's University8, University of Cologne9, Sogang University10, Soonchunhyang University11, Copenhagen University Hospital12, Uppsala University13, The Chinese University of Hong Kong14, Duke University15, Emory University16, University of Pennsylvania17, University of Otago18, University of Verona19
TL;DR: A genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly with myocardial infarction in six different populations.
Abstract: Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
TL;DR: Mounting evidence indicates multiple reciprocal interactions of E-cadherin and β-catenin with EMT-inducing transcriptional repressors to stabilize an invasive mesenchymal phenotype of epithelial tumor cells.
Abstract: The embryonic program ‘epithelial-mesenchymal transition’ (EMT) is activated during tumor invasion in disseminating cancer cells. Characteristic to these cells is a loss of E-cadherin expression, which can be mediated by EMT-inducing transcriptional repressors, e.g. ZEB1. Consequences of a loss of E-cadherin are an impairment of cell-cell adhesion, which allows detachment of cells, and nuclear localization of β-catenin. In addition to an accumulation of cancer stem cells, nuclear β-catenin induces a gene expression pattern favoring tumor invasion, and mounting evidence indicates multiple reciprocal interactions of E-cadherin and β-catenin with EMT-inducing transcriptional repressors to stabilize an invasive mesenchymal phenotype of epithelial tumor cells.
TL;DR: This review focuses on recent knowledge of the behavioral, endocrine, genetic, and neural effects of OT and AVP in humans and provides a synthesis of recent advances made in the effort to implicate the oxytocinergic system in the treatment of psychopathological states.
TL;DR: The present review provides an overview of the DUSP family before focusing on atypical DUSPs, emerging as a group of proteins with vastly diverse substrate specificity and function.
Abstract: DUSPs (dual-specificity phosphatases) are a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate. DUSPs have been implicated as major modulators of critical signalling pathways that are dysregulated in various diseases. DUSPs can be divided into six subgroups on the basis of sequence similarity that include slingshots, PRLs (phosphatases of regenerating liver), Cdc14 phosphatases (Cdc is cell division cycle), PTENs (phosphatase and tensin homologues deleted on chromosome 10), myotubularins, MKPs (mitogen-activated protein kinase phosphatases) and atypical DUSPs. Of these subgroups, a great deal of research has focused on the characterization of the MKPs. As their name suggests, MKPs dephosphorylate MAPK (mitogen-activated protein kinase) proteins ERK (extracellular-signal-regulated kinase), JNK (c-Jun N-terminal kinase) and p38 with specificity distinct from that of individual MKP proteins. Atypical DUSPs are mostly of low-molecular-mass and lack the N-terminal CH2 (Cdc25 homology 2) domain common to MKPs. The discovery of most atypical DUSPs has occurred in the last 6 years, which has initiated a large amount of interest in their role and regulation. In the past, atypical DUSPs have generally been grouped together with the MKPs and characterized for their role in MAPK signalling cascades. Indeed, some have been shown to dephosphorylate MAPKs. The current literature hints at the potential of the atypical DUSPs as important signalling regulators, but is crowded with conflicting reports. The present review provides an overview of the DUSP family before focusing on atypical DUSPs, emerging as a group of proteins with vastly diverse substrate specificity and function.
TL;DR: This review puts the current knowledge of marine picocyanobacterial genomics into an environmental context and presents previously unpublished genomic information arising from extensive genomic comparisons in order to provide insights into the adaptations of these marine microbes to their environment and how they are reflected at the genomic level.
Abstract: Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus numerically dominate the picophytoplankton of the world ocean, making a key contribution to global primary production. Prochlorococcus was isolated around 20 years ago and is probably the most abundant photosynthetic organism on Earth. The genus comprises specific ecotypes which are phylogenetically distinct and differ markedly in their photophysiology, allowing growth over a broad range of light and nutrient conditions within the 45 degrees N to 40 degrees S latitudinal belt that they occupy. Synechococcus and Prochlorococcus are closely related, together forming a discrete picophytoplankton clade, but are distinguishable by their possession of dissimilar light-harvesting apparatuses and differences in cell size and elemental composition. Synechococcus strains have a ubiquitous oceanic distribution compared to that of Prochlorococcus strains and are characterized by phylogenetically discrete lineages with a wide range of pigmentation. In this review, we put our current knowledge of marine picocyanobacterial genomics into an environmental context and present previously unpublished genomic information arising from extensive genomic comparisons in order to provide insights into the adaptations of these marine microbes to their environment and how they are reflected at the genomic level.
TL;DR: It is suggested that UV‐B‐specific interaction of COP1 and UVR8 in the nucleus is a very early step in signalling and responsible for the plant's coordinated response toUV‐B ensuring UV‐ B acclimation and protection in the natural environment.
Abstract: The ultraviolet-B (UV-B) portion of the solar radiation functions as an environmental signal for which plants have evolved specific and sensitive UV-B perception systems. The UV-B-specific UV RESPONSE LOCUS 8 (UVR8) and the multifunctional E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) are key regulators of the UV-B response. We show here that uvr8-null mutants are deficient in UV-B-induced photomorphogenesis and hypersensitive to UV-B stress, whereas overexpression of UVR8 results in enhanced UV-B photomorphogenesis, acclimation and tolerance to UV-B stress. By using sun simulators, we provide evidence at the physiological level that UV-B acclimation mediated by the UV-B-specific photoregulatory pathway is indeed required for survival in sunlight. At the molecular level, we demonstrate that the wild type but not the mutant UVR8 and COP1 proteins directly interact in a UV-B-dependent, rapid manner in planta. These data collectively suggest that UV-B-specific interaction of COP1 and UVR8 in the nucleus is a very early step in signalling and responsible for the plant's coordinated response to UV-B ensuring UV-B acclimation and protection in the natural environment.
TL;DR: Surgical treatment of displaced proximal humeral fractures with use of the locking proximal Humeral plate that was evaluated in the present study can lead to a good functional outcome provided that the correct surgical technique is used.
Abstract: Background The treatment of unstable displaced proximal humeral fractures, especially in the elderly, remains controversial. The objective of the present prospective, multicenter, observational study was to evaluate the functional outcome and the complication rate after open reduction and internal fixation of proximal humeral fractures with use of a locking proximal humeral plate. Methods One hundred and eighty-seven patients (mean age, 62.9 +/- 15.7 years) with an acute proximal humeral fracture were managed with open reduction and internal fixation with a locking proximal humeral plate. At the three-month, six-month, and one-year follow-up examinations, 165 (88%), 158 (84%), and 155 (83%) of the 187 patients were assessed with regard to pain, shoulder mobility, and strength. The Constant score was determined at each interval, and the Disabilities of the Arm, Shoulder and Hand (DASH) score was determined for the injured and contralateral extremities at the time of the one-year follow-up. Results Between three months and one year, the mean range of motion and the mean Constant score for the injured shoulders improved substantially. Twelve months after surgery, the mean Constant score for the injured side was 70.6 +/- 13.7 points, corresponding to 85.1% +/- 14.0% of the score for the contralateral side. The mean DASH score at the time of the one-year follow-up was 15.2 +/- 16.8 points. Sixty-two complications were encountered in fifty-two (34%) of 155 patients at the time of the one-year follow-up. Twenty-five complications (40%) were related to incorrect surgical technique and were present at the end of the operative procedure. The most common complication, noted in twenty-one (14%) of 155 patients, was intraoperative screw perforation of the humeral head. Twenty-nine patients (19%) had an unplanned second operation within twelve months after the fracture. Conclusions Surgical treatment of displaced proximal humeral fractures with use of the locking proximal humeral plate that was evaluated in the present study can lead to a good functional outcome provided that the correct surgical technique is used. Because many of the complications were related to incorrect surgical technique, it behooves the treating surgeon to perform the operation correctly to avoid iatrogenic errors.
TL;DR: Thermally reduced graphite oxides (TrGO) with specific surface areas of 600 to 950 m(2) · g(-1) were obtained by oxidation of graphite followed by thermal expansion at 600 °C.
Abstract: Exfoliation of expanded GO represents an attractive route to functionalized graphenes as versatile 2D carbon nanomaterials and components of a wide variety of polymer nanocomposites. Thermally reduced graphite oxides (TrGO) with specific surface areas of 600 to 950 m2 · g−1 were obtained by oxidation of graphite followed by thermal expansion at 600 °C. Thermal post treatment at 700 °C and 1 000 °C increased carbon content (81 to 97 wt.-%) and lowered resistivity (1 600 to 50 Ω · cm). During melt extrusion with PC, iPP, SAN and PA6, exfoliation afforded uniformly dispersed graphenes with aspect ratio > 200. In comparison to conventional 0D and 1D carbon nanoparticles, TrGO afforded nanocomposites with improved stiffness and lower percolation threshold. Recent progress and new strategies in development of functionalized graphenes and graphene-based nanocomposites are highlighted.
TL;DR: The greatest challenges to boron chemistry are still the synthesis of monophasic products in macroscopic quantities and in the form of single crystals, the unequivocal identification and determination of crystal structures, and a thorough understanding of their electronic situation.
Abstract: Many of the fundamental questions regarding the solid-state chemistry of boron are still unsolved, more than 200 years after its discovery. Recently, theoretical work on the existence and stability of known and new modifications of the element combined with high-pressure and high-temperature experiments have revealed new aspects. A lot has also happened over the last few years in the field of reactions between boron and main group elements. Binary compounds such as B(6)O, MgB(2), LiB(1-x), Na(3)B(20), and CaB(6) have caused much excitement, but the electron-precise, colorless boride carbides Li(2)B(12)C(2), LiB(13)C(2), and MgB(12)C(2) as well as the graphite analogue BeB(2)C(2) also deserve special attention. Physical properties such as hardness, superconductivity, neutron scattering length, and thermoelectricity have also made boron-rich compounds attractive to materials research and for applications. The greatest challenges to boron chemistry, however, are still the synthesis of monophasic products in macroscopic quantities and in the form of single crystals, the unequivocal identification and determination of crystal structures, and a thorough understanding of their electronic situation. Linked polyhedra are the dominating structural elements of the boron-rich compounds of the main group elements. In many cases, their structures can be derived from those that have been assigned to modifications of the element. Again, even these require a critical revision and discussion.
TL;DR: This work has identified the intermediate cleaving peptidase ICP55, which removes an amino acid from a characteristic set of MPP-generated N-termini, solving the controversial situation ofMPP specificity and suggesting that Icp55 converts instable intermediates into stable proteins.
TL;DR: This work shows that alternative functional programs of hematopoietic stem cells (HSCs) are governed by gradual differences in methylation levels and identifies DNA methylation as an essential epigenetic mechanism to protect stem cells from premature activation of predominant differentiation programs.
Abstract: DNA methylation is a dynamic epigenetic mark that undergoes extensive changes during differentiation of self-renewing stem cells. However, whether these changes are the cause or consequence of stem cell fate remains unknown. Here, we show that alternative functional programs of hematopoietic stem cells (HSCs) are governed by gradual differences in methylation levels. Constitutive methylation is essential for HSC self-renewal but dispensable for homing, cell cycle control and suppression of apoptosis. Notably, HSCs from mice with reduced DNA methyltransferase 1 activity cannot suppress key myeloerythroid regulators and thus can differentiate into myeloerythroid, but not lymphoid, progeny. A similar methylation dosage effect controls stem cell function in leukemia. These data identify DNA methylation as an essential epigenetic mechanism to protect stem cells from premature activation of predominant differentiation programs and suggest that methylation dynamics determine stem cell functions in tissue homeostasis and cancer.
TL;DR: Quantitative VA measures are thus obtainable in the very low-vision range using FrACT, which can reproducibly quantify VA in the CF and HM range.
Abstract: The Freiburg Visual Acuity Test (FrACT) has been suggested as a promising test for quantifying the visual acuity (VA) of patients with very low vision, a condition often classified using the semi-quantitative clinical scale “counting fingers” (CF), “hand motion” (HM), “light perception” (LP) and “no light perception”. The present study was designed to assess FrACT performance in a sizable number of CF, HM, and LP patients in order to generate a setting for future clinical studies in the low vision range. We examined a total of 41 patients (LP, n = 11; CF, n = 15; HM, n = 15) with various eye diseases (e.g., diabetic retinopathy, ARMD), covering the clinical VA scale from LP to CF. The FrACT optotypes were presented at a distance of 50 cm on a 17-inch LCD monitor with four random orientations. After training, two FrACT measurements (test and retest) were taken, each comprising 30 trials. FrACT measures reproducibly the VA of CF and HM patients. In CF patients, FrACT resulted in a mean logMAR = 1.98 ± 0.24 (corresponding to a decimal VA of 0.010), for HM in a mean logMAR = 2.28 ± 0.15 (corresponding to a decimal VA of 0.0052). In all LP patients the FrACT values were close to what would be obtained by random guessing. The mean test–retest 95% confidence interval was 0.21 logMAR for CF patients and 0.31 logMAR for HM respectively. Test-retest variability declined from 24 to 30 trials, showing that at least 30 trials are necessary. FrACT can reproducibly quantify VA in the CF and HM range. We observed a floor effect for LP, and it was not quantifiable further. Quantitative VA measures are thus obtainable in the very low-vision range using FrACT.
TL;DR: In these letters, the authors outlined measures to allow precise estimation of gene expression in quantitative RT-PCR.
Abstract: Two recent letters to the editor of The Plant Cell ([Gutierrez et al, 2008][1]; [Udvardi et al, 2008][2]) highlighted the importance of following correct experimental protocol in quantitative RT-PCR (qRT-PCR) In these letters, the authors outlined measures to allow precise estimation of gene
Proceedings Article•
19 Sep 2009TL;DR: A new admissible heuristic called the landmark cut heuristic is introduced, which compares favourably with the state of the art in terms of heuristic accuracy and overall performance.
Abstract: Current heuristic estimators for classical domain-independent planning are usually based on one of four ideas: delete relaxations, critical paths, abstractions, and, most recently, landmarks. Previously, these different ideas for deriving heuristic functions were largely unconnected.
We prove that admissible heuristics based on these ideas are in fact very closely related. Exploiting this relationship, we introduce a new admissible heuristic called the landmark cut heuristic, which compares favourably with the state of the art in terms of heuristic accuracy and overall performance.
TL;DR: The 3D metal-organic framework (MOF) (3)(infinity) is found to be a reversibly dehydratable-hydratable water-stable MOF material with a large loading spread as a candidate for solid adsorbents in heat transformation cycles for refrigeration, heat pumping, and heat storage.
Abstract: The 3D metal−organic framework (MOF) 3∞{[Ni3(μ3-btc)2(μ4-btre)2(μ-H2O)2]·∼22H2O} is found to be a reversibly dehydratable−hydratable water-stable MOF material with a large loading spread of 210 g/kg as a candidate for solid adsorbents in heat transformation cycles for refrigeration, heat pumping, and heat storage.
TL;DR: A micromachined 252-channel ECoG (electrocorticogram)-electrode array, which is made of a thin polyimide foil substrate enclosing sputtered platinum electrode sites and conductor paths, designed to cover large parts of a hemisphere of a macaque monkey's cortex.
Abstract: We present a micromachined 252-channel ECoG (electrocorticogram)-electrode array, which is made of a thin polyimide foil substrate enclosing sputtered platinum electrode sites and conductor paths. The array subtends an area of approximately 35 mm by 60 mm and is designed to cover large parts of a hemisphere of a macaque monkey’s cortex. Eight omnetics connectors are directly soldered to the foil. This leads to a compact assembly size which enables a chronic implantation of the array and allows free movements of the animal between the recording sessions. The electrode sites are 1 mm in diameter and were characterized by electrochemical impedance spectroscopy. At 1 kHz, the electrode impedances vary between