Revisiting algorithms for generating surrogate time series.

The method of surrogates is one of the key concepts of nonlinear data analysis. Here, we demonstrate that commonly used algorithms for generating surrogates often fail to generate truly linear time series. Rather, they create surrogate realizations with Fourier phase correlations leading to nondetections of nonlinearities. We argue that reliable surrogates can only be generated, if one tests separately for static and dynamic nonlinearities.

B cell-activating factor: its clinical significance in multiple myeloma patients.

B cell-activating factor (BAFF) is a cytokine that plays a major role in the maintenance of normal B-cell development and homeostasis. It has been suggested that in multiple myeloma (MM) it might have regulatory effects on the proliferation and viability of malignant plasma cells. The aim of this study was to evaluate serum levels of BAFF in 52 newly diagnosed MM patients, with varying disease severity, in order to see the correlations between BAFF and indices of MM activity, such as interleukin-6, C-reactive protein, lactate dehydrogenase, and beta-2 microglobulin, and to explore the clinical significance of BAFF in predicting the disease activity of MM. We found increased BAFF serum levels in MM patients, increased in advanced stages, and decreased in plateau phase. We also found significant correlations between BAFF serum levels with the above parameters of disease activity. We conclude that BAFF may play an important role in pathogenesis of MM, could be used as a marker of disease activity, and a possible therapeutic target.

Molecular pathways of lymphangiogenesis and lymph node metastasis in head and neck cancer.

Metastasis to regional lymph nodes constitutes the main route toward progression and dissemination of head and neck carcinoma; at the same time it is the most significant adverse prognostic indicator for this disease. In recent years, significant focus has been given on the molecular mechanisms behind lymph node metastasis of head and neck cancer. The aim of this study is to assess the role of growth factor expression and function in association with lymph node metastasis and overall prognosis of head and neck cancer. Current literature, searching for experimental data regarding the molecular pathways of lymph node dissemination of head and neck cancer, is reviewed giving special emphasis on the expression and prognostic significance of specific growth factors. Members of the vascular endothelial growth factor (VEGF), mostly VEGF-C and VEGF-D, with their action through the receptors VEGFR-3 and VEGFR-2, constitute the most extensively studied growth factors associated with lymphangiogenesis so far. High expression of these as well as other molecules, including angiopoietins, insulin-like growth factor, and fibroblast growth factor, has been associated with lymph node metastasis and poor prognosis in head and neck squamous cell carcinoma. Numerous growth factors seem to play an important role regarding the lymph node metastatic potential of head and neck cancer. Further research is necessary in order to further clarify the molecular pathways and introduce novel therapeutic options.

Ontogeny of the digestive tract in sharpsnout sea bream Diplodus puntazzo (Cetti, 1777).

The ontogeny of the digestive tract was studied histologically and histochemically in sharpsnout sea bream Diplodus puntazzo from hatching (0 DAH, Days After Hatching) until day 57 (57 DAH). At hatching, the digestive tract appeared as a histologically undifferentiated straight tube lying dorsally to the yolk sac. When the mouth opened at 3 DAH, the digestive tract was differentiated into buccopharynx, oesophagus, incipient stomach and intestine. The pancreas, liver and gall bladder were also differentiated at this stage and both the bile and pancreatic duct had opened into the anterior intestine. Active feeding began in 50% of larvae at 4 DAH, although permanence of yolk reserves until 7 DAH suggests a period of both endogenous and exogenous feeding. Nutrient absorption was first visible from 5 DAH, as colourless supra- and infranuclear vacuoles in the anterior intestinal mucosa, suggesting a lipid content, as well as supranuclear, eosinophilic vacuoles, containing protein, in the posterior intestinal mucosa. Early caecal development could be detected from 10 DAH, whereas gastric glands appeared at 30 DAH, indicating the transition from larval to juvenile stage and the acquisition of an adult mode of digestion. Goblet cells appeared in the digestive tract of sharpsnout sea bream larvae shortly after first feeding. The mucus content of goblet cells varied with the digestive region and, in the buccal cavity and oesophagus, also with the developmental phase. This study provides knowledge for better husbandry practices in the aquaculture industry, as well as for the implementation of future nutritional studies.

A cell-based model for the photoacclimation and CO(2)-acclimation of the photosynthetic apparatus.

We have developed a mathematical model based on the underlying mechanisms concerning the responses of the photosynthetic apparatus of a microalga cell which grows under constant incident light intensity and ambient CO(2) concentration. Photosynthesis involves light and carbon-fixation reactions which are mutually dependent and affect each other, but existing models for photosynthesis don't account for both reactions at once. Our modeling approach allows us to derive distinct equations for the rates of oxygen production, NADPH production, carbon dioxide fixation, carbohydrate production, and rejected energy, which are generally different. The production rates of the photosynthesis products are hyperbolic functions of light and CO(2) concentration. The model predicts that in the absence of photoinhibition, CO(2)-inhibition, photorespiration, and chlororespiration, a cell acclimated to high light and/or CO(2) concentration has higher photosynthetic capacity and lower photosynthetic efficiency than does a cell acclimated to low conditions. This results in crossing between the two curves which represent the oxygen production rates and carbon fixation rates in low and high conditions. Finally, in the absence of photoinhibition and CO(2)-inhibition, the model predicts the carbohydrate production rate in terms of both light intensity and CO(2) concentration.

The International Measurement Evaluation Programme, IMEP-8: carbon and oxygen isotope ratios in CO(2).

In IMEP-8, two samples of high purity CO(2)(g), with different carbon and oxygen isotope ratios were distributed to 27 participants, originating from 14 countries and from various isotopic measurement domains (geochemistry, atmospheric and food chemistry), but particularly set up for food laboratories. In total 19 laboratories reported results. The outcome of this comparison exercise shows that the laboratories reported carbon and oxygen isotope results in good agreement with the reference values across the domains. The reported results for delta(13)C(VPDB) (carbon) for both materials are within 1 per thousand. However, for the reported results of delta(18)O(VPDB) (oxygen) for both materials the overall spread of the reported results is about 11 per thousand. Within this spread two distinct groups of participants can be identified, where the results within each group vary about 2 per thousand. The latter seems to be caused by calculation errors by participants of the reporting delta(18)O(VPDB) values. As requested, participants also reported the isotope amount ratio for carbon and oxygen in the CO(2) samples. For carbon, all reported results for both materials agree with the isotope ratio value, which can be traced back to the value reported by Craig. For oxygen, all results are in good agreement and deviate by a maximum of 0.5% from the reference values measured at IRMM. Work carried out indicates the carbon isotope ratio, for both samples IMEP-8A and IMEP-8B, differ from those reported by Craig by as much as 1.2%. In the case of oxygen, this deviation is far smaller. Both data sets, i.e. the one realised by Craig and the one realised at IRMM, demonstrate traceability to SI. It is clear that both values significantly disagree.

Secure medical digital libraries.

In this paper, a secure medical digital library is presented. It is based on the CORBA specifications for distributed systems. The described approach relies on a three-tier architecture. Interaction between the medical digital library and its users is achieved through a Web server. The choice of employing Web technology for the dissemination of medical data has many advantages compared to older approaches, but also poses extra requirements that need to be fulfilled. Thus, special attention is paid to the distinguished nature of such medical data, whose integrity and confidentiality should be preserved at all costs. This is achieved through the employment of Trusted Third Parties (TTP) technology for the support of the required security services. Additionally, the proposed digital library employs smartcards for the management of the various security tokens that are used from the above services.

International Measurement Evaluation Programme: IMEP-9, trace elements in water.

The International Measurement Evaluation Programme (IMEP) is an interlaboratory comparison scheme, founded, owned and coordinated by the Institute for Reference Materials and Measurements (IRMM) since 1988. IMEP-9 is the third round of trace elements in water evaluation following IMEP-3 and IMEP-6. Reference values for 15 elements stating total concentrations and combined uncertainties (according to GUM) were established. The reference values were established mainly by isotope dilution mass spectrometry (IDMS) as a primary method of measurement, and values traceable to the SI were obtained. The four elements that could not be certified by IDMS were assigned values by means of other measurement techniques. Results from 201 laboratories from 35 countries and four continents were evaluated against the reference values and the comparability between the laboratories is presented graphically.

Nodular glomerulosclerosis secondary to mu heavy chain deposits.

mu heavy chain deposition disease is very rare. We report the first case of glomerulonephritis in a woman without evidence of hematopoietic malignancy. Nodular glomerulosclerosis and monotypic mu heavy chain mesangial deposits were identified by immunofluorescence without kappa or lambda deposits. Electron microscopy showed fibrillar mesangial deposits of 16-18 nm in diameter. Serum immunoglobulins, cryoglobulins, serum immunoelectrophoresis, and immunofixation, bone marrow biopsy, and Bence Jones proteins in urine were negative. The patient has stable renal disease and is free of malignancy 6 years after the initial occurrence of proteinuria.

A secure Web-based medical digital library architecture based on TTPs.

In this paper, a secure medical digital library architecture is presented, that is based on the CORBA specifications for distributed systems. Special attention is given to the distinguished nature of medical data, whose integrity and confidentiality should be preserved at all costs. This is achieved through the employment of Trusted Third Parties (TTP) technology for the support of the required security services.

SI-traceable certification of Cu, Cr, Cd and Pb in sediment and fly ash candidate reference materials.

Many fields in environmental analytical chemistry deal with very low limits and thresholds as set by governmental legislations or transnational regulations. The need for the accuracy, comparability and traceability of analytical measurements in environmental analytical chemistry has significantly increased and total uncertainties are even asked for by accreditation bodies of environmental laboratories. This paper addresses achieving these goals to guarantee accuracy, quality control, quality assurance or validation of a method by means of certified reference materials. The assessment of analytical results in certified reference materials must be as accurate as possible and every single step has to be fully evaluated. This paper presents the SI-traceable certification of Cu, Cr, Cd and Pb contents in geological and environmentally relevant matrices (three sediments and one fly ash sample). Certification was achieved using isotope dilution (ID) ICPMS as a primary method of measurement. In order to reduce significantly the number of analytical steps and intermediate samples a multiple spiking approach was developed. The full methodology is documented and total uncertainty budgets are calculated for all certified values. A non-element specific sample digestion process was optimised. All wet chemical digestion methods examined resulted in a more or less pronounced amount of precipitate. It is demonstrated that these precipitates originate mainly from secondary formation of fluorides (essentially CaF2) and that their formation takes place after isotopic equilibration. The contribution to the total uncertainty of the final values resulting from the formation of such precipitates was in general < 0.1% for all investigated elements. Other sources of uncertainty scrutinised included the moisture content determination, procedural blank determination, cross-contamination from the different spike materials, correction for spectral interferences, instrumental background and deadtime effects, as well as the use of either certified values or IUPAC data in the IDMS equation. The average elemental content in the sediment samples was 30-130 micrograms g-1 for Pb, 0.5-3 micrograms g-1 for Cd and 50-70 micrograms g-1 for Cu. Cr was measured in one sample and was about 60 micrograms g-1. The concentrations in the fly ash sample were up to 2 orders of magnitude higher. Expanded uncertainty for the investigated elements was about 3% (coverae factor k = 2) except for Cr, (measured by high resolution ICPMS), for which the expanded uncertainty was about 7% (k = 2).