Showing papers by "University of Hamburg published in 1998"

Queueing Networks and Markov Chains: Modeling and Performance Evaluation with Computer Science Applications

Abstract: Preface to the Second Edition. Preface to the First Edition. 1. Introduction. 1.1 Motivation. 1.2 Methodological Background. 1.3 Basics of Probability and Statistics. 2. Markov Chains. 2.1 Markov Processes. 2.2 Performance Measures. 2.3 Generation Methods. 3. Steady-State Solutions of Markov Chains. 3.1 Solution for a Birth Death Process. 3.2 Matrix-Geometric Method: Quasi-Birth-Death Process. 3.3 Hessenberg Matrix: Non-Markovian Queues. 3.4 Numerical Solution: Direct Methods. 3.5 Numerical Solution: Iterative Methods. 3.6 Comparison of Numerical Solution Methods. 4. Steady-State Aggregation/Disaggregation Methods. 4.1 Courtois' Approximate Method. 4.2 Takahashi's Iterative Method. 5. Transient Solution of Markov Chains. 5.1 Transient Analysis Using Exact Methods. 5.2 Aggregation of Stiff Markov Chains. 6. Single Station Queueing Systems. 6.1 Notation. 6.2 Markovian Queues. 6.3 Non-Markovian Queues. 6.4 Priority Queues. 6.5 Asymmetric Queues. 6.6 Queues with Batch Service and Batch Arrivals. 6.7 Retrial Queues. 6.8 Special Classes of Point Arrival Processes. 7. Queueing Networks. 7.1 Definitions and Notation. 7.2 Performance Measures. 7.3 Product-Form Queueing Networks. 8. Algorithms for Product-Form Networks. 8.1 The Convolution Algorithm. 8.2 The Mean Value Analysis. 8.3 Flow Equivalent Server Method. 8.4 Summary. 9. Approximation Algorithms for Product-Form Networks. 9.1 Approximations Based on the MVA. 9.2 Summation Method. 9.3 Bottapprox Method. 9.4 Bounds Analysis. 9.5 Summary. 10. Algorithms for Non-Product-Form Networks. 10.1 Nonexponential Distributions. 10.2 Different Service Times at FCFS Nodes. 10.3 Priority Networks. 10.4 Simultaneous Resource Possession. 10.5 Prograrns with Internal Concurrency. 10.6 Parallel Processing. 10.7 Networks with Asymmetric Nodes. 10.8 Networks with Blocking. 10.9 Networks with Batch Service. 11. Discrete-Event Simulation. 11.1 Introduction to Simulation. 11.2 Simulative or Analytic Solution? 11.3 Classification of Simulation Models. 11.4 Classification of Tools in DES. 11.5 The Role of Probability and Statistics in Simulation. 11.6 Applications. 12. Performance Analysis Tools. 12.1 PEPSY. 12.2 SPNP. 12. 3 MOSEL-2. 12.4 SHARPE. 12.5 Characteristics of Some Tools. 13. Applications. 13.1 Case Studies of Queueing Networks. 13.2 Case Studies of Markov Chains. 13.3 Case Studies of Hierarchical Models. Glossary. Bibliography. Index.

WinXAS: a program for X-ray absorption spectroscopy data analysis under MS-Windows.

Abstract: WinXAS is a new X-ray absorption spectroscopy (XAS) data-analysis program. It runs under the operating system MS-Windows 95/NT and offers several unique features. It has a user-friendly graphical environment and is capable of reading a variety of data formats. It contains a number of useful numerical algorithms beyond those used in conventional XAS analysis and offers a simple interface to the ab-initio theoretical code FEFF. The availability of fast macros in WinXAS makes it particularly useful for on-line data examination at synchrotron radiation facilities during XAS experiments as well as for the analysis of multiple-scan data such as those from time-resolved experiments.

A Potassium Channel Mutation in Neonatal Human Epilepsy

Abstract: Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene (KCNQ2) located on 20q13.3 was isolated and found to be expressed in brain. Expression of KCNQ2 in frog (Xenopus laevis) oocytes led to potassium-selective currents that activated slowly with depolarization. In a large pedigree with BFNC, a five-base pair insertion would delete more than 300 amino acids from the KCNQ2 carboxyl terminus. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.

Assessing health-related quality of life in chronically ill children with the German KINDL: first psychometric and content analytical results.

Abstract: Health-related quality of life is increasingly being considered as a relevant end-point and outcome criterion in evaluating the effects of medical treatment. While in adults quality of life instruments have been developed in terms of generic as well as disease-specific measures, quality of life assessment and children is a relatively new area. The current paper describes the application of a German generic quality of life instrument for children (the KINDL) in a group of 45 chronically ill children suffering from diabetes or asthma in comparison to 45 age- and gender-matched healthy children. The results of psychometric testing in these populations showed that the German KINDL is a reliable, valid and practical instrument to assess the health-related quality of life of children which should be supplemented by disease-specific modules and needs to be further tested in clinical populations.

Combined Molecular and Conventional Analyses of Nitrifying Bacterium Diversity in Activated Sludge: Nitrosococcus mobilis and Nitrospira-Like Bacteria as Dominant Populations

Abstract: The ammonia-oxidizing and nitrite-oxidizing bacterial populations occurring in the nitrifying activated sludge of an industrial wastewater treatment plant receiving sewage with high ammonia concentrations were studied by use of a polyphasic approach. In situ hybridization with a set of hierarchical 16S rRNA-targeted probes for ammonia-oxidizing bacteria revealed the dominance of Nitrosococcus mobilis-like bacteria. The phylogenetic affiliation suggested by fluorescent in situ hybridization (FISH) was confirmed by isolation of N. mobilis as the numerically dominant ammonia oxidizer and subsequent comparative 16S rRNA gene (rDNA) sequence and DNA-DNA hybridization analyses. For molecular fine-scale analysis of the ammonia-oxidizing population, a partial stretch of the gene encoding the active-site polypeptide of ammonia monooxygenase (amoA) was amplified from total DNA extracted from ammonia oxidizer isolates and from activated sludge. However, comparative sequence analysis of 13 amoA clone sequences from activated sludge demonstrated that these sequences were highly similar to each other and to the corresponding amoA gene fragments of Nitrosomonas europaea Nm50 and the N. mobilis isolate. The unexpected high sequence similarity between the amoA gene fragments of the N. mobilis isolate and N. europaea indicates a possible lateral gene transfer event. Although a Nitrobacter strain was isolated, members of the nitrite-oxidizing genus Nitrobacter were not detectable in the activated sludge by in situ hybridization. Therefore, we used the rRNA approach to investigate the abundance of other well-known nitrite-oxidizing bacterial genera. Three different methods were used for DNA extraction from the activated sludge. For each DNA preparation, almost full-length genes encoding small-subunit rRNA were separately amplified and used to generate three 16S rDNA libraries. By comparative sequence analysis, 2 of 60 randomly selected clones could be assigned to the nitrite-oxidizing bacteria of the genus Nitrospira. Based on these clone sequences, a specific 16S rRNA-targeted probe was developed. FISH of the activated sludge with this probe demonstrated that Nitrospira-like bacteria were present in significant numbers (9% of the total bacterial counts) and frequently occurred in coaggregated microcolonies with N. mobilis.

SOX10 mutations in patients with Waardenburg-Hirschsprung disease.

Abstract: Waardenburg syndrome (WS; deafness with pigmentary abnormalities) and Hirschsprung's disease (HSCR; aganglionic megacolon) are congenital disorders caused by defective function of the embryonic neural crest. WS and HSCR are associated in patients with Waardenburg-Shah syndrome (WS4), whose symptoms are reminiscent of the white coat-spotting and aganglionic megacolon displayed by the mouse mutants Dom (Dominant megacolon), piebald-lethal (sl) and lethal spotting (ls). The sl and ls phenotypes are caused by mutations in the genes encoding the Endothelin-B receptor (Ednrb) and Endothelin 3 (Edn3), respectively. The identification of Sox10 as the gene mutated in Dom mice (B.H. et al., manuscript submitted) prompted us to analyse the role of its human homologue SOX10 in neural crest defects. Here we show that patients from four families with WS4 have mutations in SOX10, whereas no mutation could be detected in patients with HSCR alone. These mutations are likely to result in haploinsufficiency of the SOX10 product. Our findings further define the locus heterogeneity of Waardenburg-Hirschsprung syndromes, and point to an essential role of SOX10 in the development of two neural crest-derived human cell lineages.

Sox10, a Novel Transcriptional Modulator in Glial Cells

Abstract: Sox proteins are characterized by possession of a DNA-binding domain with similarity to the high-mobility group domain of the sex determining factor SRY. Here, we report on Sox10, a novel protein with predominant expression in glial cells of the nervous system. During development Sox10 first appeared in the forming neural crest and continued to be expressed as these cells contributed to the forming PNS and finally differentiated into Schwann cells. In the CNS, Sox10 transcripts were originally confined to glial precursors and later detected in oligodendrocytes of the adult brain. Functional studies failed to reveal autonomous transcriptional activity for Sox10. Instead, Sox10 functioned synergistically with the POU domain protein Tst-1/Oct6/SCIP with which it is coexpressed during certain stages of Schwann cell development. Synergy depended on binding to adjacent sites in target promoters, was mediated by the N-terminal regions of both proteins, and could not be observed between Sox10 and several other POU domain proteins. Interestingly, Sox10 also modulated the function of Pax3 and Krox-20, two other transcription factors involved in Schwann cell development. We propose a role for Sox10 in conferring cell specificity to the function of other transcription factors in developing and mature glia.

Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K + channels causes epilepsy

Abstract: Epilepsy affects more than 0.5% of the world's population and has a large genetic component1. It is due to an electrical hyperexcitability in the central nervous system. Potassium channels are important regulators of electrical signalling, and benign familial neonatal convulsions (BFNC), an autosomal dominant epilepsy of infancy, is caused by mutations in the KCNQ2 or the KCNQ3 potassium channel genes2,3,4. Here we show that KCNQ2 and KCNQ3 are distributed broadly in brain with expression patterns that largely overlap. Expression in Xenopus oocytes indicates the formation of heteromeric KCNQ2/KCNQ3 potassium channels with currents that are at least tenfold larger than those of the respective homomeric channels. KCNQ2/KCNQ3 currents can be increased by intracellular cyclic AMP, an effect that depends on an intact phosphorylation site in the KCNQ2 amino terminus. KCNQ2 and KCNQ3 mutations identified in BFNC pedigrees compromised the function of the respective subunits, but exerted no dominant-negative effect on KCNQ2/KCNQ3 heteromeric channels. We predict that a 25% loss of heteromeric KCNQ2/KCNQ3-channel function is sufficient to cause the electrical hyperexcitability in BFNC. Drugs raising intracellular cAMP may prove beneficial in this form of epilepsy.

Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice.

Abstract: 1,25-Dihydroxyvitamin D3 plays a major role in intestinal calcium transport. To determine what phenotypic abnormalities observed in vitamin D receptor (VDR)-ablated mice are secondary to impaired intestinal calcium absorption rather than receptor deficiency, mineral ion levels were normalized by dietary means. VDR-ablated mice and control littermates were fed a diet that has been shown to prevent secondary hyperparathyroidism in vitamin D-deficient rats. This diet normalized growth and random serum ionized calcium levels in the VDR-ablated mice. The correction of ionized calcium levels prevented the development of parathyroid hyperplasia and the increases in PTH messenger RNA synthesis and in serum PTH levels. VDR-ablated animals fed this diet did not develop rickets or osteomalacia. However, alopecia was still observed in the VDR-ablated mice with normal mineral ions, suggesting that the VDR is required for normal hair growth. This study demonstrates that normalization of mineral ion homeostasis can prevent the development of hyperparathyroidism, osteomalacia, and rickets in the absence of the genomic actions of 1,25-dihydroxyvitamin D3.

Intravascular ultrasound-guided optimized stent deployment Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study)

Abstract: Objectives A study was set up to validate the safety and feasibility of intravascular ultrasound-guided stenting without subsequent anticoagulation, and its impact on the 6 months restenosis rate. Methods The study was designed to be multicentred, prospective, and observational. Results One hundred and sixty-one patients with stable angina and a de novo coronary artery lesion were enrolled. In four patients, the implantation of a Palmaz–Schatz (with spiral bridge) stent had failed. One of these four patients died 3 days following bypass surgery. In two other patients, intravascular ultrasound assessment was not performed. One hundred and twenty-five of the remaining 155 patients (81%) were treated with aspirin (100mg.day−1), because all three criteria for optimized stent expansion were met. Twenty-two of the remaining 38 patients (25%), in whom at least one criterion was not met were treated with aspirin and acenocoumarol (3 months, INR 2·5–3·5), while 16 patients only received aspirin. Stent thrombosis was documented in two patients (1·3%) for which repeat angioplasty was performed. During the hospital stay, there were no deaths or Q-wave myocardial infarctions. Five patients (3·2%) sustained a non-Q-wave myocardial infarction. During the follow-up period (198±38 days, complete for all patients, except one), one patient (0·6%) sustained a Q-wave myocardial infarction, one (0·6%) underwent bypass surgery, and repeat angioplasty was performed in nine patients (5·7%). In two of the nine patients, repeat angioplasty involved another lesion. Therefore, the target lesion revascularization rate during follow-up was 4·5% (seven patients).At quantitative coronary angiography, the minimal lumen diameter (mean±SD) increased from 1·12± 0·34mm before to 2·89±0·35mm after stenting. Repeat angiography at 6 months was performed in 144 patients (92%). The minimal lumen diameter at follow-up was 2·12±0·67mm. Restenosis (diameter stenosis of 50% or more) was documented in 12 patients or 8·3%. When the two patients with documented stent thrombosis are included, the restenosis rate amounts to 9·7%. Conclusions These data confirm that, in selected patients, stents can safely be implanted without the use of systemic anticoagulation, provided optimal stent expansion is achieved. The exact role of intravascular ultrasound in the achievement of these results needs to be established by appropriately designed studies. In the meantime, intra-vascular ultrasound coupled with the Palmaz–Schatz stent incorporating a spiral bridge, may have contributed considerably to the immediate angiographic outcome, which in turn may explain the favourable clinical and angiographic outcome at 6 months.

Wet-chemical synthesis of doped colloidal nanoparticles : yvo4:ln (ln = eu, sm, dy)

Abstract: Colloidal solutions and redispersible powders of nanocrystalline, lanthanide-doped YVO4 have been prepared via a hydrothermal method at 200 °C. High-resolution transmission electron micrographs of size-selected samples show highly crystalline particles ranging in size from about 10 to 30 nm. The particles exhibit the tetragonal zircon structure known for bulk material. Upon UV excitation of the vanadate host, the energy is transferred to the lanthanide ion and strong luminescence (f−f transitions) is observed. By analyzing line splitting and intensity pattern in the luminescence spectrum of the europium-doped sample, we are able to verify that the dopant ions enter the same lattice site as in bulk material despite the nanocrystalline nature of the sample and the low-temperature synthesis. For YVO4:Eu nanoparticles a luminescence quantum yield of 15% at room-temperature was observed.

Importance of Extracellular Polymeric Substances from Thiobacillus ferrooxidans for Bioleaching

Abstract: Leaching bacteria such as Thiobacillus ferrooxidans attach to pyrite or sulfur by means of extracellular polymeric substances (EPS) (lipopolysaccharides). The primary attachment to pyrite at pH 2 is mediated by exopolymer-complexed iron(III) ions in an electrochemical interaction with the negatively charged pyrite surface. EPS from sulfur cells possess increased hydrophobic properties and do not attach to pyrite, indicating adaptability to the substrate or substratum.

Phylogeography of mitochondrial DNA in western Europe

Abstract: For most of the past century, prehistorians have had to rely on the fossil and archaeological records in order to reconstruct the past. In the last few decades, this evidence has been substantially supplemented from classical human genetics. More recently, phylogenetic analyses of DNA sequences that incorporate geographical information have provided a high-resolution tool for the investigation of prehistoric demographic events, such as founder effects and population expansions. These events can be dated using a molecular clock when the mutation rate and founder haplotypes are known. We have previously applied such methods to sequence data from the mitochondrial DNA control region, to suggest that most extant mitochondrial sequences in western Europe have a local ancestry in the Early Upper Palaeolithic, with a smaller proportion arriving from the Near East in the Neolithic. Here, we describe a cladistic notation for mitochondrial variation and expand upon our earlier analysis to present a more detailed portrait of the European mitochondrial record.

ClC-5, the chloride channel mutated in Dent’s disease, colocalizes with the proton pump in endocytotically active kidney cells

Abstract: Loss-of-function mutations of the ClC-5 chloride channel lead to Dent’s disease, a syndrome characterized by low molecular weight proteinuria, hypercalciuria, and kidney stones. We show that ClC-5 is expressed in renal proximal tubule cells, which normally endocytose proteins passing the glomerular filter. Expression is highest below the brush border in a region densely packed with endocytotic vesicles, where ClC-5 colocalizes with the H+-ATPase and with internalized proteins early after uptake. In intercalated cells of the collecting duct it again localizes to apical intracellular vesicles and colocalizes with the proton pump in α-intercalated cells. In transfected cells, ClC-5 colocalizes with endocytosed α2-macroglobulin. Cotransfection with a GTPase-deficient rab5 mutant leads to enlarged early endosomes that stain for ClC-5. We suggest that ClC-5 may be essential for proximal tubular endocytosis by providing an electrical shunt necessary for the efficient acidification of vesicles in the endocytotic pathway, explaining the proteinuria observed in Dent’s disease.

mtDNA Analysis Reveals a Major Late Paleolithic Population Expansion from Southwestern to Northeastern Europe

Abstract: mtDNA sequence variation was studied in 419 individuals from nine Eurasian populations, by high-resolution RFLP analysis, and it was followed by sequencing of the control region of a subset of these mtDNAs and a detailed survey of previously published data from numerous other European populations. This analysis revealed that a major Paleolithic population expansion from the "Atlantic zone" (southwestern Europe) occurred 10,000-15,000 years ago, after the Last Glacial Maximum. As an mtDNA marker for this expansion we identified haplogroup V, an autochthonous European haplogroup, which most likely originated in the northern Iberian peninsula or southwestern France at about the time of the Younger Dryas. Its sister haplogroup, H, which is distributed throughout the entire range of Caucasoid populations and which originated in the Near East approximately 25,000-30,000 years ago, also took part in this expansion, thus rendering it by far the most frequent (40%-60%) haplogroup in western Europe. Subsequent migrations after the Younger Dryas eventually carried those "Atlantic" mtDNAs into central and northern Europe. This scenario, already implied by archaeological records, is given overwhelming support from both the distribution of the autochthonous European Y chromosome type 15, as detected by the probes 49a/f, and the synthetic maps of nuclear data.

Experimental tests of factorization in charmless nonleptonic two-body B decays

Abstract: Using a theoretical framework based on the next-to-leading-order QCD-improved effective Hamiltonian and a factorization ansatz for the hadronic matrix elements of the four-quark operators, we reassess branching fractions in two-body nonleptonic decays $\stackrel{\ensuremath{\rightarrow}}{B}PP,PV,VV,$ involving the lowest-lying light pseudoscalar $(P)$ and vector $(V)$ mesons in the standard model. We work out the parametric dependence of the decay rates, making use of the currently available information on the weak mixing matrix elements, form factors, decay constants, and quark masses. Using the sensitivity of the decay rates on the effective number of colors, ${N}_{c},$ as a criterion of theoretical predictivity, we classify all the current-current (tree) and penguin transitions in five different classes. The recently measured charmless two-body $\stackrel{\ensuremath{\rightarrow}}{B}\mathrm{PP}$ decays ${(B}^{+}\ensuremath{\rightarrow}{K}^{+}{\ensuremath{\eta}}^{\ensuremath{'}}, {B}^{0}\ensuremath{\rightarrow}{K}^{0}{\ensuremath{\eta}}^{\ensuremath{'}}, {B}^{0}\ensuremath{\rightarrow}{K}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}, {B}^{+}\ensuremath{\rightarrow}{\ensuremath{\pi}}^{+}{K}^{0},$ and charge conjugates) are dominated by the ${N}_{c}$-stable QCD penguin transitions (class-IV transitions) and their estimates are consistent with the data. The measured charmless $\stackrel{\ensuremath{\rightarrow}}{B}\mathrm{PV} {(B}^{+}\ensuremath{\rightarrow}\ensuremath{\omega}{K}^{+}, {B}^{+}\ensuremath{\rightarrow}\ensuremath{\omega}{h}^{+})$ and $\stackrel{\ensuremath{\rightarrow}}{B}\mathrm{VV}$ transition $(\stackrel{\ensuremath{\rightarrow}}{B}\ensuremath{\varphi}{K}^{*}),$ on the other hand, belong to the penguin (class-V) and tree (class-III) transitions. The class-V penguin transitions are ${N}_{c}$ sensitive and/or involve large cancellations among competing amplitudes, making their decay rates in general more difficult to predict. Some of these transitions may also receive significant contributions from annihilation and/or final state interactions. We propose a number of tests of the factorization framework in terms of the ratios of branching ratios for some selected $\stackrel{\ensuremath{\rightarrow}}{B}{h}_{1}{h}_{2}$ decays involving light hadrons ${h}_{1}$ and ${h}_{2},$ which depend only moderately on the form factors. We also propose a set of measurements to determine the effective coefficients of the current-current and QCD penguin operators. The potential impact of $\stackrel{\ensuremath{\rightarrow}}{B}{h}_{1}{h}_{2}$ decays on the CKM phenomenology is emphasized by analyzing a number of decay rates in the factorization framework.

Neutral Higgs-Boson Pair Production at Hadron Colliders: QCD Corrections

Abstract: Neutral Higgs-boson-pair production provides the possibility of studying the trilinear Higgs couplings at future high-energy colliders. We present the QCD corrections to the gluon-initiated processes in the limit of a heavy top quark in the loops and the Drell-Yan-like pair production of scalar and pseudoscalar Higgs particles. The pp cross sections are discussed for CERN LHC energies within the standard model and its minimal supersymmetric extension. The QCD corrections are large, enhancing the total cross sections significantly.

Mutation of the Sry-related Sox10 gene in Dominant megacolon, a mouse model for human Hirschsprung disease

Abstract: The spontaneous mouse mutant Dominant megacolon (Dom) is a valuable model for the study of human congenital megacolon (Hirschsprung disease). Here we report that the defect in the Dom mouse is caused by mutation of the gene encoding the Sry-related transcription factor Sox10. This assignment is based on (i) colocalization of the Sox10 gene with the Dom mutation on chromosome 15; (ii) altered Sox10 expression in the gut and in neural-crest derived structures of cranial ganglia of Dom mice; (iii) presence of a frameshift in the Sox10 coding region, and (iv) functional inactivation of the resulting truncated protein. These results identify the transcriptional regulator Sox10 as an essential factor in mouse neural crest development and as a further candidate gene for human Hirschsprung disease, especially in cases where it is associated with features of Waardenburg syndrome.

Extended drainage versus resection in surgery for chronic pancreatitis: a prospective randomized trial comparing the longitudinal pancreaticojejunostomy combined with local pancreatic head excision with the pylorus-preserving pancreatoduodenectomy.

Abstract: OBJECTIVE: To analyze the efficacy of extended drainage--that is, longitudinal pancreaticojejunostomy combined with local pancreatic head excision (LPJ-LPHE)-and pylorus-preserving pancreatoduodenectomy (PPPD) in terms of pain relief, control of complications arising from adjacent organs, and quality of life. SUMMARY BACKGROUND DATA: Based on the hypotheses of pain origin (ductal hypertension and perineural inflammatory infiltration), drainage and resection constitute the main principles of surgery for chronic pancreatitis. METHODS: Sixty-one patients were randomly allocated to either LPJ-LPHE (n = 31) or PPPD (n = 30). The interval between symptoms and surgery ranged from 12 months to 10 years (mean 5.1 years). In addition to routine pancreatic diagnostic workup, a multidimensional psychometric quality-of-life questionnaire and a pain score were used. Endocrine and exocrine functions were assessed in terms of oral glucose tolerance and serum concentrations of insulin, C-peptide, and HbA1c, as well as fecal chymotrypsin and pancreolauryl testing. During a median follow-up of 24 months (range 12 to 36), patients were reassessed in the outpatient clinic. RESULTS: One patient died of cardiovascular failure in the LPJ-LPHE group (3.2%); there were no deaths in the PPPD group. Overall, the rate of in-hospital complications was 19.4% in the LPJ-LPHE group and 53.3% in the PPPD group, including delayed gastric emptying in 9 of 30 patients (30%; p < 0.05). Complications of adjacent organs were definitively resolved in 93.5% in the LPJ-LPHE group and in 100% in the PPPD group. The pain score decreased by 94% after LPJ-LPHE and by 95% after PPPD. Global quality of life improved by 71% in the LPJ-LPHE group and by 43% in the PPPD group (p < 0.01). CONCLUSIONS: Both procedures are equally effective in terms of pain relief and definitive control of complications affecting adjacent organs, but extended drainage by LPJ-LPHE provides a better quality of life.

Migration of vascular plants to secondary woodlands in southern sweden

Abstract: 1 We studied the migration of field layer plants across ecotones between ancient woodlands and recent deciduous woods on former arable land varying in age between 30 and 75 years. 2 Number and percentage cover of woodland species in recent woods decreased with increasing distance to the ancient woods, and increased with the age of the recent woods, indicating dispersal limitation during secondary succession. 3 Colonization by typical woodland plants was observed in 183 of 200 species × site combinations. In 72 combinations, a colonization front was characterized by logarithmic or linear decrease in species cover, indicating establishment of isolated individuals and gradual infill of gaps. This pattern was most common in ant-dispersed species and less frequent in species with adhesive or ingested seeds. 4 Migration rates were calculated for 49 woodland species. Mean migration rates based on maximum cover in recent woods varied from 0.00 to 1.00 m year−1 between species, with a median migration rate of 0.30 m year−1. Migration rates calculated on occurrence of the farthest individual ranged from 0.00 to 1.25 m year−1, with a median rate of 0.53 m year−1. 5 Ant-dispersed species had lower migration rates based on maximum cover compared with species with adhesive or ingested seeds. No differences between dispersal modes were found when comparing migration rates based on the farthest individuals. Most of the calculated migration rates (84%) exceeded the rate of possible vegetative spread of woodland species. 6 Establishment of a field layer vegetation in secondary woods comparable to that of the adjacent ancient stands proceeded at a rate of c. 0.3–0.5 m year−1. We conclude that scale and intensity of temperate forest management should be adjusted to the relatively slow migration of the field layer flora in order to enable complete recovery during a management cycle.

The Neural Cell Adhesion Molecule Is a Receptor for Rabies Virus

Abstract: Previous reports strongly suggest that, in addition to the nicotinic acetylcholine receptor, rabies virus can use other, as-yet-unidentified receptors. We found that laboratory cell lines susceptible to rabies virus infection express the neural cell adhesion molecule (NCAM) (CD56) on their surface, whereas resistant cells do not, supporting the idea that NCAM could be a rabies virus receptor. We observed that (i) incubation with rabies virus decreases the surface expression of NCAM; (ii) treatment of susceptible cells with heparan sulfate, a ligand for NCAM, or with NCAM antibodies significantly reduces the rabies virus infection; and (iii) preincubation of rabies virus inoculum with soluble NCAM protein as a receptor decoy drastically neutralizes the capacity of rabies virus to infect susceptible cells. Moreover, we demonstrated that transfection of resistant L fibroblasts with the NCAM-encoding gene induces rabies virus susceptibility whereas absence of NCAM in the primary cortical cell cultures prepared from NCAM-deficient mice reduces the rabies virus infection and virus production. This provides evidence that NCAM is an in vitro receptor for the rabies virus. Moreover, the in vivo relevance for the use of NCAM as a receptor was demonstrated by the infection of NCAM-deficient mice, in which rabies mortality was delayed and brain invasion by rabies virus was drastically restricted. Our results showed that NCAM, which is expressed mainly in the adult nervous system, plays an important role in rabies infection. However, it cannot be excluded that receptors other than NCAM are utilized. Thus, the description of NCAM as a new rabies virus receptor would be another example of the use by viruses of more than one receptor to gain entry into the host.

mtDNA Haplogroup X: An Ancient Link between Europe/Western Asia and North America?

Abstract: Summary On the basis of comprehensive RFLP analysis, it has been inferred that ∼97% of Native American mtDNAs belong to one of four major founding mtDNA lineages, designated haplogroups "A"–"D." It has been proposed that a fifth mtDNA haplogroup (haplogroup X) represents a minor founding lineage in Native Americans. Unlike haplogroups A–D, haplogroup X is also found at low frequencies in modern European populations. To investigate the origins, diversity, and continental relationships of this haplogroup, we performed mtDNA high-resolution RFLP and complete control region (CR) sequence analysis on 22 putative Native American haplogroup X and 14 putative European haplogroup X mtDNAs. The results identified a consensus haplogroup X motif that characterizes our European and Native American samples. Among Native Americans, haplogroup X appears to be essentially restricted to northern Amerindian groups, including the Ojibwa, the Nuu-Chah-Nulth, the Sioux, and the Yakima, although we also observed this haplogroup in the Na-Dene–speaking Navajo. Median network analysis indicated that European and Native American haplogroup X mtDNAs, although distinct, nevertheless are distantly related to each other. Time estimates for the arrival of X in North America are 12,000–36,000 years ago, depending on the number of assumed founders, thus supporting the conclusion that the peoples harboring haplogroup X were among the original founders of Native American populations. To date, haplogroup X has not been unambiguously identified in Asia, raising the possibility that some Native American founders were of Caucasian ancestry.

Potassium Channel Distribution, Clustering, and Function in Remyelinating Rat Axons

Abstract: The K+ channel α-subunits Kv1.1 and Kv1.2 and the cytoplasmic β-subunit Kvβ2 were detected by immunofluorescence microscopy and found to be colocalized at juxtaparanodes in normal adult rat sciatic nerve. After demyelination by intraneural injection of lysolecithin, and during remyelination, the subcellular distributions of Kv1.1, Kv1.2, and Kvβ2 were reorganized. At 6 d postinjection (dpi), axons were stripped of myelin, and K+ channels were found to be dispersed across zones that extended into both nodal and internodal regions; a few days later they were undetectable. By 10 dpi, remyelination was underway, but Kv1.1 immunoreactivity was absent at newly forming nodes of Ranvier. By 14 dpi, K+ channels were detected but were in the nodal gap between Schwann cells. By 19 dpi, most new nodes had Kv1.1, Kv1.2, and Kvβ2, which precisely colocalized. However, this nodal distribution was transient. By 24 dpi, the majority of K+ channels was clustered within paranodal regions of remyelinated axons, leaving a gap that overlapped with Na+ channel immunoreactivity. Inhibition of Schwann cell proliferation delayed both remyelination and the development of the K+ channel distributions described. Conduction studies indicate that neither 4-aminopyridine (4-AP) nor tetraethylammonium alters normal nerve conduction. However, during remyelination, 4-AP profoundly increased both compound action potential amplitude and duration. The level of this effect matched closely the nodal presence of these voltage-dependent K+channels. Our results suggest that K+ channels may have a significant effect on conduction during remyelination and that Schwann cells are important in K+ channel redistribution and clustering.

On the statistical properties of deterministic simulation models for mobile fading channels

Abstract: Rice's (9144, 1945) sum of sinusoids can be used for an efficient approximation of colored Gaussian noise processes and is therefore of great importance to the software and hardware realization of mobile fading channel models. Although several methods can be found in the literature for the computation of the parameters characterizing a proper set of sinusoids, less is reported about the statistical properties of the resulting (deterministic) simulation model. In this paper, not only is the simulation model's amplitude and phase probability density function (PDF) investigated, but also higher order statistics [e.g., level-crossing rate (LCR) and average duration of fades (ADFs)]. It is shown that due to the deterministic nature of the simulation model, analytical expressions for the PDF of the amplitude and phase, autocorrelation function (ACF), crosscorrelation function (CCF), LCR, and ADFs can be derived. We also propose a new procedure for the determination of an optimal set of sinusoids, i.e., the method results for a given number of sinusoids in an optimal approximation of Gaussian, Rayleigh, and Rice processes with given Doppler power spectral density (PSD) properties. It is shown that the new method can easily be applied to the approximation of various other kinds of distribution functions, such as the Nakagami (1960) and Weibull distributions. Moreover, a quasi-optimal parameter computation method is presented.

Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: First results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation

Abstract: In a multicentre trial involving 20 transplant centres from 10 countries haematopoietic stem cells were obtained either from the bone marrow of 33 sibling donors or from the peripheral blood of 33 such donors after administration of filgrastim (10 μg/kg/day). The haematopoietic stem cells were infused into their HLA-identical recipients suffering from acute leukaemias in remission or chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT. Pain and haematoma at the harvest site and mild anaemia were the most frequent complaints of BM donors. Severe or life-threatening complications were not seen with any type of harvest procedure. Time to platelet recovery greater than 20 × 109/l was 15 days (95% confidence interval (CI) 13–16 days) in the PBPCT group and 19 days (CI 16–25) in the BMT group. Time to neutrophil recovery greater than 0.5 × 109/l was 14 days (CI 12–15 days) in the PBPCT group as compared to 15 days (CI 15–16 days) in the BMT group. The numbers of platelet transfusions administered to PBPCT and BMT patients were 12 (range: 1–28) and 10 (range: 3–39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18 patients (54%) transplanted with PBPC developed acute GVHD of grades II–IV; acute GVHD of grades III or IV developed in six (18%) and seven (21%) patients, respectively. Kaplan–Meier plots for transplant-related mortality until day 100 and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no significant differences. Administration of filgrastim and leukapheresis in normal donors were feasible and well tolerated. The number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC. Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted in earlier platelet engraftment. The incidence of moderate to severe acute GVHD, transplant-related mortality, and leukaemia-free survival did not show striking differences. Further investigation of allogeneic PBPCT as a substitute for allogeneic BMT is warranted.

A New Hot Spot for Mutations in the ret Protooncogene Causing Familial Medullary Thyroid Carcinoma and Multiple Endocrine Neoplasia Type 2A

Abstract: One hundred and eighty-one families with multiple endocrine neoplasia type 2A (MEN-2A) or familial medullary thyroid carcinoma (FMTC) have been investigated for mutations in the ret protooncogene in Germany. In 8 families with FMTC or MEN-2A, no mutation could be detected in the cysteine-rich domain encoded in exons 10 and 11 of the ret protooncogene. DNA sequencing of additional exons (no. 13-15) revealed rare noncysteine mutations in 3 families (codons 631, 768, and 844). In contrast to these rare events, heterozygous missense mutations in exon 13, codons 790 and 791, were found in 5 families (4 with MTC only; 1 family with MTC and pheochromocytoma) and 11 patients with apparently sporadic tumors. Two different mutations in codon 790 (TTG-->TTT, TTG-->TTC; Leu790Phe) and one mutation in codon 791 (TAT-->TTT; Tyr791Phe) created a phenylalanine residue. We conclude that codons 790 and 791 of the ret protooncogene represent a new hot spot for FMTC/MEN-2A causing mutations. With the discovery of these considerably common mutations in codons 790 and 791 and the identification of some rare mutations, 100% of the German FMTC/MEN-2A families could be characterized by a mutation in the ret protooncogene.