Showing papers by "Martin Luther University of Halle-Wittenberg published in 2006"

European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium

Abstract: European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium Furio Pacini, Martin Schlumberger, Henning Dralle, Rossella Elisei, Johannes W A Smit, Wilmar Wiersinga and the European Thyroid Cancer Taskforce Section of Endocrinology and Metabolism, University of Siena, Via Bracci, 53100 Siena, Italy, Service de Medicine Nucleaire, Institut Gustave Roussy, Villejuif, France, Department of General, Visceral and Vascular Surgery, University of Halle, Germany, Department of Endocrinology, University of Pisa, Italy, Department of Endocrinology and Metabolic Disease, Leiden University Medical Center, The Netherlands and Department of Endocrinology and Metabolism, University of Amsterdam, The Netherlands

Insights into social insects from the genome of the honeybee Apis mellifera

Abstract: Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.

Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis Based on Aggregate Data

Abstract: Purpose This systematic review and meta-analysis were performed to assess the efficacy and tolerability of chemotherapy in patients with advanced gastric cancer. Methods Randomized phase II and III clinical trials on first-line chemotherapy in advanced gastric cancer were identified by electronic searches of Medline, Embase, the Cochrane Controlled Trials Register, and Cancerlit; hand searches of relevant abstract books and reference lists; and contact to experts. Meta-analysis was performed using the fixed-effect model. Overall survival, reported as hazard ratio (HR) with 95% CI, was the primary outcome measure. Results Analysis of chemotherapy versus best supportive care (HR = 0.39; 95% CI, 0.28 to 0.52) and combination versus single agent, mainly fluorouracil (FU) -based chemotherapy (HR = 0.83; 95% CI = 0.74 to 0.93) showed significant overall survival benefits in favor of chemotherapy and combination chemotherapy, respectively. In addition, comparisons of FU/cisplatin-containing regimens with versus ...

Bent-core liquid crystals: polar order, superstructural chirality and spontaneous desymmetrisation in soft matter systems

Abstract: An overview on the recent developments in the field of liquid crystalline bent-core molecules (so-called banana liquid crystals) is given. After some basic issues, dealing with general aspects of the systematisation of the mesophases, development of polar order and chirality in this class of LC systems and explaining some general structure–property relationships, we focus on fascinating new developments in this field, such as modulated, undulated and columnar phases, so-called B7 phases, phase biaxiality, ferroelectric and antiferroelectric polar order in smectic and columnar phases, amplification and switching of chirality and the spontaneous formation of superstructural and supramolecular chirality.

Stabilization of Soil Organic Matter: Association with Minerals or Chemical Recalcitrance?

Abstract: Soil organic matter (OM) can be stabilized against decomposition by association with minerals, by its inherent recalcitrance and by occlusion in aggregates. However, the relative contribution of these factors to OM stabilization is yet unknown. We analyzed pool size and isotopic composition (14C, 13C) of mineral-protected and recalcitrant OM in 12 subsurface horizons from 10 acidic forest soils. The results were related to properties of the mineral phase and to OM composition as revealed by CPMAS 13C-NMR and CuO oxidation. Stable OM was defined as that material which survived treatment of soils with 6 wt% sodium hypochlorite (NaOCl). Mineral-protected OM was extracted by subsequent dissolution of minerals by 10% hydrofluoric acid (HF). Organic matter resistant against NaOCl and insoluble in HF was considered as recalcitrant OM. Hypochlorite removed primarily 14C-modern OM. Of the stable organic carbon (OC), amounting to 2.4–20.6 g kg−1 soil, mineral dissolution released on average 73%. Poorly crystalline Fe and Al phases (Feo, Alo) and crystalline Fe oxides (Fed−o) explained 86% of the variability of mineral-protected OC. Atomic Cp/(Fe+Al)p ratios of 1.3–6.5 suggest that a portion of stable OM was associated with polymeric Fe and Al species. Recalcitrant OC (0.4–6.5 g kg−1 soil) contributed on average 27% to stable OC and the amount was not correlated with any mineralogical property. Recalcitrant OC had lower Δ14C and δ13C values than mineral-protected OC and was mainly composed of aliphatic (56%) and O-alkyl (13%) C moieties. Lignin phenols were only present in small amounts in either mineral-protected or recalcitrant OM (mean 4.3 and 0.2 g kg−1 OC). The results confirm that stabilization of OM by interaction with poorly crystalline minerals and polymeric metal species is the most important mechanism for preservation of OM in these acid subsoil horizons.

Drugs, their targets and the nature and number of drug targets

Abstract: What is a drug target? And how many such targets are there? Here, we consider the nature of drug targets, and by classifying known drug substances on the basis of the discussed principles we provide an estimation of the total number of current drug targets.

Clinical presentation and penetrance of Pheochromocytoma/ Paraganglioma syndromes.

Abstract: Context: The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma/paraganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations. Objective: Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations. Design, Setting, and Participants: The International SDH Consortium studied 116 individuals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland. Main Outcome Measures: Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, patholo...

Overcoming the stratum corneum: the modulation of skin penetration. A review.

Abstract: It is preferred that topically administered drugs act either dermally or transdermally. For that reason they have to penetrate into the deeper skin layers or permeate the skin. The outermost layer of the human skin, the stratum corneum, is responsible for its barrier function. Most topically administered drugs do not have the ability to penetrate the stratum corneum. In these cases modulations of the skin penetration profiles of these drugs and skin barrier manipulations are necessary. A skin penetration enhancement can be achieved either chemically, physically or by use of appropriate formulations. Numerous chemical compounds have been evaluated for penetration-enhancing activity, and different modes of action have been identified for skin penetration enhancement. In addition to chemical methods, skin penetration of drugs can be improved by physical options such as iontophoresis and phonophoresis, as well as by combinations of both chemical and physical methods or by combinations of several physical methods. There are cases where skin penetration of the drug used in the formulation is not the aim of the topical administration. Penetration reducers can be used to prevent chemicals entering the systemic circulation. This article concentrates on the progress made mainly over the last decade by use of chemical penetration enhancers. The different action modes of these substances are explained, including the basic principles of the physical skin penetration enhancement techniques and examples for their application.

Investigation, Treatment, and Monitoring of Late-Onset Hypogonadism in Males: ISA, ISSAM, EAU, EAA, and ASA Recommendations

Abstract: Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. Cross-sectional and longitudinal data indicate that the testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men (1–4). The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. This has been comprehensively reviewed and summarized by the Institute of Medicine in ‘Testosterone and Aging: Clinical Research Directions’ (5). Long-term data on the effects of testosterone treatment in the older population are limited mainly to effects on body composition and bone mass (6–11). Key questions of the effects of testosterone on patient reported outcomes and functional benefits that may retard physical or mental frailty of the elderly or improve the quality of life are not yet available. Specific risk data on the prostate and cardiovascular systems are needed.

Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets

Abstract: Tissue factor (TF) is an essential cofactor for the activation of blood coagulation in vivo. We now report that quiescent human platelets express TF pre-mRNA and, in response to activation, splice this intronic-rich message into mature mRNA. Splicing of TF pre-mRNA is associated with increased TF protein expression, procoagulant activity, and accelerated formation of clots. Pre-mRNA splicing is controlled by Cdc2-like kinase (Clk)1, and interruption of Clk1 signaling prevents TF from accumulating in activated platelets. Elevated intravascular TF has been reported in a variety of prothrombotic diseases, but there is debate as to whether anucleate platelets—the key cellular effector of thrombosis—express TF. Our studies demonstrate that human platelets use Clk1-dependent splicing pathways to generate TF protein in response to cellular activation. We propose that platelet-derived TF contributes to the propagation and stabilization of a thrombus.

Long-term persistence and multifractality of precipitation and river runoff records

Abstract: [1] We discuss and compare the multifractal temporal scaling properties of precipitation and river discharge records on large timescales. To detect long-term correlations and multifractal behavior in the presence of trends, we apply recently developed methods (detrended fluctuation analysis (DFA) and multifractal DFA) that can systematically detect nonstationarities and overcome trends in the data at all timescales. We find that above some crossover time that usually is several weeks, the daily runoffs are characterized by an asymptotic scaling exponent that indicates a slow power law decay of the runoff autocorrelation function and varies from river to river in a wide range. Below the crossovers, pronounced short-term correlations occur. In contrast, most of the precipitation series show scaling behavior corresponding to a rapid decay of the autocorrelation function. For the multifractal characterization of the data we determine the generalized Hurst exponents and fit them by three operational models. While the fits based on the universal multifractal model describe well the scaling behavior of the positive moments in nearly all runoff and precipitation records, positive as well as negative moments are consistent with two-parameter fits from a modified version of the multiplicative cascade model for all runoff records and most of the precipitation records. For some precipitation records with weak multifractality, however, a simple bifractal characterization gives the best fit of the data.

Phase III Trial of Capecitabine Plus Oxaliplatin As Adjuvant Therapy for Stage III Colon Cancer: A Planned Safety Analysis in 1,864 Patients

Abstract: Purpose To report the results of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil/leucovorin (FU/LV) as adjuvant therapy for stage III colon cancer. Patients and Methods Patients with stage III colon carcinoma were randomly assigned to receive either XELOX (intravenous oxaliplatin plus oral capecitabine; 3-week cycle for eight cycles) or standard intravenous bolus FU/LV administered as the Mayo Clinic (Mayo; Rochester, MN) or Roswell Park (RP; Buffalo, NY) regimen for a similar length of time. A total of 1,886 patients were randomly assigned. Results The safety population comprised 1,864 patients, of whom 938 received XELOX and 926 received FU/LV. Most treatment-related adverse events (AEs) occurred at similar rates in both treatment arms. However, patients receiving XELOX experienced less all-grade diarrhea, alopecia, and more neurosensory toxicity, vomiting, and hand-foot syndrome than those patients receiving FU/LV. Compared with M...

Thrombolytic therapy in pregnancy

Abstract: Pregnancy due to its physiological changes is a procoagulant state. The rate of cardiac valve prosthesis thrombosis, deep venous thrombosis and pulmonary embolism are all increased. Thrombolytic therapy with tissue plasminogen activator (rt-PA) is an approved therapy for ischemic stroke, myocardial infarction, pulmonary embolism and thrombosis of cardiac valve prosthesis. However, there are no data from controlled randomized trials in pregnant patients. Thrombolytic therapy has been rarely used in pregnancy with only 28 cases of rt-PA thrombolysis reported in the literature so far. Indications for rt-PA thrombolysis were stroke (n = 10), thrombosis of cardiac valve prosthesis (n = 7), pulmonary embolism (n = 7), deep venous thrombosis (n = 3), and myocardial infarction (n = 1). Remarkably, all thrombosis of cardiac valve prostheses occurred after switching from warfarin to heparin in order to prevent teratogenicity and fetal loss. Two patients died (7%) and three suffered from complications that were managed conservatively (11%). In another three patients thrombolysis was not successful. Thrombolysis complication rates were similar compared to non-pregnant patients for the above mentioned indications. Six out of the 26 fetus from surviving mothers died (23%), three of them after induced abortion for maternal reasons (12%). A likely causal relation to the prior thrombolysis could only be established in two fetal fatalities (8%). None of the live born children suffered a permanent deficit. Considering that rt-PA does not cross the placenta and taking into account that the complication rates do not exceed those of large randomised controlled trials thrombolytic therapy should not be withheld in pregnant patients in case of life-threatening or potentially debilitating thrombembolic disease.

Open versus closed treatment of fractures of the mandibular condylar process–a prospective randomized multi-centre study

Abstract: Summary Aim The aim of this international prospective randomized multi-centre study was to compare operative and conservative treatment of displaced condylar fractures of the mandible. Methods and patients Out of a total of 88 randomized patients from 7 centres, 66 patients with 79 fractures of the mandibular condylar process completed the study and were evaluated. All fractures were displaced, being either angulated between 10° and 45° or the ascending ramus was shortened by more than 2 mm. The follow-up examinations 6 weeks and 6 months following treatment included evaluation of radiographic measurements, clinical, functional and subjective parameters including visual analogue scale for pain and the Mandibular Function Impairment Questionnaire index for dysfunction. Results Correct anatomical position of the fragments was achieved significantly more often in the operative group in contrast to the closed treatment group. Regarding mouth opening/lateral excursion/protrusion, significant (p=0.01) differences were observed between both groups (open 47/16/7 mm versus closed 41/13/5 mm). The visual analogue scoring revealed significant (p=0.03) differences with less pain in the operative treatment group (2.9 open versus 13.5 closed). The Mandibular Function Impairment Questionnaire index recorded a significant (p=0.001) difference with less pain and discomfort in the open treatment group (10.5 versus 2.4 points). Conclusion Both treatment options for condylar fractures of the mandible yielded acceptable results. However, operative treatment, irrespective of the method of internal fixation used, was superior in all objective and subjective functional parameters.

Complete genome of the mutualistic, N2-fixing grass endophyte Azoarcus sp. strain BH72

Abstract: Azoarcus sp. strain BH72, a mutualistic endophyte of rice and other grasses, is of agrobiotechnological interest because it supplies biologically fixed nitrogen to its host and colonizes plants in remarkably high numbers without eliciting disease symptoms. The complete genome sequence is 4,376,040-bp long and contains 3,992 predicted protein-coding sequences. Genome comparison with the Azoarcus-related soil bacterium strain EbN1 revealed a surprisingly low degree of synteny. Coding sequences involved in the synthesis of surface components potentially important for plant-microbe interactions were more closely related to those of plant-associated bacteria. Strain BH72 appears to be 'disarmed' compared to plant pathogens, having only a few enzymes that degrade plant cell walls; it lacks type III and IV secretion systems, related toxins and an N-acyl homoserine lactones-based communication system. The genome contains remarkably few mobile elements, indicating a low rate of recent gene transfer that is presumably due to adaptation to a stable, low-stress microenvironment.

Measurement of the Bending Strength of Vapor-Liquid-Solid Grown Silicon Nanowires

Abstract: The fracture strength of silicon nanowires grown on a [111] silicon substrate by the vapor-liquid-solid process was measured. The nanowires, with diameters between 100 and 200 nm and a typical length of 2 Im, were subjected to bending tests using an atomic force microscopy setup inside a scanning electron microscope. The average strength calculated from the maximum nanowire deflection before fracture was around 12 GPa, which is 6% of the Young’s modulus of silicon along the nanowire direction. This value is close to the theoretical fracture strength, which indicates that surface or volume defects, if present, play only a minor role in fracture initiation. Nanowires (NWs) are of interdisciplinary interest to applications in the fields of biomedical sensing, nano- and optoelectronics and photovoltaics due to their electrical, optical, mechanical, and geometrical properties that may deviate substantially from bulk. 1 To name some particularly exciting applications, the reader is referred to the following list: (i) high-frequency electromechanical resonators, 2 (ii) high-aspect ratio tips for surface probe microscopy, 3 (iii) sensor array for electrical detection of cancer markers, 4 (iv) Si NW arrays for photovoltaics, 5 and (v) nanoscale light-emitting diodes. 6 For all these applications the mechanical stability of the NWs is essential for their atomic scale manipulation, functionalization, or integration into device schemes. Several methods were used in the past to access the mechanical properties of silicon NWs and nanobeams. An atomic force microscope (AFM) was used for bending tests of single crystal, micromachined silicon beams (from 1 mm down to 200 nm in width, beam axis oriented in [110] direction). No change in Young’s modulus, but an increase in bending strength by a factor of up to 38 was observed from the millimeter down to the nanometer scale. 7 AFM measurements were also done on silicon NWs (from 10 to 100 nm in diameter, grown along the [111] direction) where a bending modulus of 186 GPa (188 GPa in bulk) was measured. 8

Long-term management impacts on soil C, N and physical fertility: Part II: Bad Lauchstadt static and extreme FYM experiments

Abstract: Manure is a source of plant nutrients and can make a valuable contribution to soil organic matter (SOM). Two experimental sites were studied on a Halpic Phaeozem soil near Bad Lauchstadt in Germany. The first experiment, called the static experiment, commenced in 1902. The impact of fresh farmyard manure (FYM) (0, 20 and 30 t ha −1 2 year −1 ) combined with P, K and N fertiliser application on total organic C (C T ), labile C (C L ), non-labile C (C NL ), total N (N T ), mean weight diameter (MWD) and unsaturated hydraulic conductivity ( K unsat ) was investigated. The second experiment commenced in 1984 and investigated the effect of extreme rates of fresh FYM applications (0, 50, 100 and 200 t ha −1 year −1 ) and cropping, or a continuous tilled fallow on the same soil properties. At both sites a nearby grassland site served as a reference. On the static experiment, FYM application increased all C fractions, particularly C L , where application of 30 t ha −1 2 year −1 increased C L by 70% compared with no FYM application. Fertiliser additions to the static experiment had a positive influence on C fractions while N T increased from both FYM and fertiliser application. MWD increased as a result of FYM application, but did not reach that of the grassland site. Both fertiliser and FYM application increased K unsat (10 mm tension) on the static experiment. In the second experiment application of 200 t ha −1 year −1 of FYM increased concentrations of C L by 173% and of C NL by 80%, compared with no FYM application to make them equivalent to, or greater than the grassland site. A continuously tilled fallow resulted in significant decreases in all C fractions, N T and MWD compared with the cropped site, while K unsat (10 mm tension) was increased on the 0 and 50 t ha −1 year −1 treatments as a result of a recent tillage. There was no difference in K unsat between the cropped and the continuous tilled fallow at FYM applications of 100 and 200 t ha −1 year −1 . There were similar significant positive correlations of all C fractions and N T with MWD on both experimental sites but the relationships were much stronger on the extreme FYM experiment. Weaker relationships of C fractions and N T with K unsat (10 mm tension) occurred for the static experimental site but these were not significant for the extreme FYM experimental site. The strongest relationship between C fractions and K unsat was with C L . This research has shown that applications of FYM can increase SOM and improve soil physical fertility. However, the potential risk of very high rates of FYM on the environment need to be taken into consideration, especially since the application of organic materials to soils is likely to increase in the future.

Histone modification and the control of heterochromatic gene silencing in Drosophila.

Abstract: Covalent modifications of histones index structurally and functionally distinct chromatin domains in eukaryotic nuclei. Drosophila with its polytene chromosomes and developed genetics allows detailed cytological as well as functional analysis of epigenetic histone modifications involved in the control of gene expression pattern during development. All H3K9 mono- and dimethylation together with all H3K27 methylation states and H4K20 trimethylation are predominant marks of pericentric heterochromatin. In euchromatin, bands and interbands are differentially indexed. H3K4 and H3K36 methylation together with H3S10 phosphorylation are predominant marks of interband regions whereas in bands different H3K27 and H4K20 methylation states are combined with acetylation of H3K9 and H3K14. Genetic dissection of heterochromatic gene silencing in position-effect variegation (PEV) by Su(var) and E(var) mutations allowed identification and functional analysis of key factors controlling the formation of heterochromatin. SU(VAR)3-9 association with heterochromatic sequences followed by H3K9 methylation initiates the establishment of repressive SU(VAR)3-9/HP1/SU(VAR)3-7 protein complexes. Differential enzymatic activities of novel point mutants demonstrate that the silencing potential of SU(VAR)3-9 is mainly determined by the kinetic properties of the HMTase reaction. In Su(var)3-9ptn a significantly enhanced enzymatic activity results in H3K9 hypermethylation, enhanced gene silencing and extensive chromatin compaction. Mutations in factors controlling active histone modification marks revealed the dynamic balance between euchromatin and heterochromatin. Further analysis and definition of Su(var) and E(var) genes in Drosophila will increase our understanding of the molecular hierarchy of processes controlling higher-order structures in chromatin.

Phase-rectified signal averaging detects quasi-periodicities in non-stationary data

Abstract: We present an efficient technique for the study of quasi-periodic oscillations in noisy, non-stationary signals, which allows the assessment of system dynamics despite phase resetting and noise. It is based on the definition of anchor points in the signal (in the simplest case increases or decreases of the signal) which are used to align (i.e., phase-rectify) the oscillatory fluctuations followed by an averaging of the surroundings of the anchor points. We give theoretical arguments for the advantage of the technique, termed phase-rectified signal averaging (PRSA), over conventional spectral analysis and show in a numerical test using surrogate heartbeat data that the threshold intensity for the detection of additional quasi-periodic components is approximately 75% lower with PRSA. With the use of different anchor point criteria PRSA is capable of separately analysing quasi-periodicities that occur during increasing or decreasing parts of the signal. We point to a variety of applications in the analysis of medical, biological, and geophysical data containing quasi-periodicities besides non-stationarities and 1 / f noise.

Organometallic benzene-vanadium wire: A one-dimensional half-metallic ferromagnet.

Abstract: Using density functional theory we perform theoretical investigations of the electronic properties of a freestanding one-dimensional organometallic vanadium-benzene wire. This system represents the limiting case of multidecker Vn(C6H6)(n+1) clusters which can be synthesized with established methods. We predict that the ground state of the wire is a 100% spin-polarized ferromagnet (half-metal). Its density of states is metallic at the Fermi energy for the minority electrons and shows a semiconductor gap for the majority electrons. We find that the half-metallic behavior is conserved up to 12% longitudinal elongation of the wire. Ab initio electron transport calculations reveal that finite size vanadium-benzene clusters coupled to ferromagnetic Ni or Co electrodes will work as nearly perfect spin filters.