Physical and CFD model used in the analysis of particles dispersion.

Air pollution, representing one of the major environmental crises affecting us all, is responsible for half a million deaths each year in Europe. This research shows a numerical model based on Computational Fluid Dynamics (CFD) and a methodology for its validation allowing to know the evolution of particles in open urban environments. In this case, the model represents an area of Gijón (Asturias), specifically chosen as it serves to highlight a location at which the daily limit values of PM10 set by the regulations are most frequently exceeded. A numerical model has been developed at a scale of 1:10,000 to simulate the dispersion of pollutants, including particulate emissions. A physical model at the same scale was built using 3D printing. This model was tested in a wind tunnel and analysed in the four main wind directions. To carry out the tests, a particle generation system was designed and manufactured, and the necessary infrastructure was built to take measurements using an optical particle meter. Results show that the numerical model meets the expected objectives and is capable of predicting the behaviour of particle dispersion in the air. The numerical model produces results in the same order of magnitude as the physical model, although there is a tendency to underestimate the maximum values with respect to the measured ones.

CFD model to study PM[Formula: see text] dispersion in large-scale open spaces.

Air pollution has become a major concern in industrial or highly populated areas. Although legislation has been enacted to limit pollution levels, air quality monitoring still needs to be carried out by stations which are located at fixed points unable to provide the spatial evolution of pollutants. This research, focused on the city of Gijón (Asturias), includes a Computational Fluid Dynamics model capable of simulating the dispersion of pollutants in a large urban environment (12x18 km[Formula: see text]). Different wind conditions were simulated with two sources of emission. The results show the influence of the terrain on the dispersion of pollutants in open spaces whilst simultaneously scrutinizing the origin of diffuse industrial pollution circulating over the city of Gijon. The simulation allows us to set limits in the areas with higher levels of contamination or to analyse the variations of particle concentration in height. Therefore, this research defines and validates a methodology to generate numerical models which grant us the opportunity to observe the spatial evolution of pollutants in large areas. This result endorses further use in other lines of research, such as the evaluation of corrective measures to improve air quality in highly polluted environments.

[The Basel Interview for Psychosis (BIP): structure, reliability and validity]. / Das Basler Interview für Psychosen (BIP): Struktur, Reliabilität und Validität.

BACKGROUND: Although several instruments have been developed to identify patients with an at-risk mental state (ARMS) for psychosis and first episode of psychosis (FEP), up to now there were no instruments for a detailed assessment of risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span in these patients. We therefore developed the Basle Interview for Psychosis (BIP). The aim of this study is to describe the development of the BIP and to report about its psychometric properties. METHODS: The BIP is a comprehensive semi-structured interview that was developed for the Basel early detection of psychoses (FePsy) study. Its items were derived from the most important risk factors and indicators of psychosis described in the literature and from several existing instruments. It contains the following six sections: 1) social and physical development and family, 2) signs and symptoms, 3) vulnerability, 4) help-seeking behavior, 5) illness insight, 6) evaluation of the interview. To estimate the inter-rater reliabilities of the items of sections 2 and 3, 20 interviews were conducted and rated by 8 well-trained raters. The factorial structure of the BIP section "signs and symptoms" was explored in a sample of 120 ARMS and 77 FEP patients. On the basis of the discovered factorial structure, we created new subscales and assessed their reliabilities and validities. RESULTS: Of the 153 studied items of sections 2 and 3, 150 (98 %) were rated with sufficiently high agreement (inter-rater reliability > 0.4). The items of section "signs and symptoms" could be grouped into 5 subscales with predominantly good to very good internal consistencies, homogeneities, and discriminant and convergent validities. Predictive validities could be demonstrated for the subscales "Positive Psychotic Symptoms", "Disturbance of Thinking" and the total score. DISCUSSION: The BIP is the first interview for comprehensively assessing risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span, which has been validated in ARMS and FEP patients. We could show that the BIP has excellent psychometric properties.

Akt2/PKBbeta-sensitive regulation of renal phosphate transport.

AIM: The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport. METHODS: The renal phosphate transporter NaPi-IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na(+) phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBbeta knockout mice (akt2(-/-)) and corresponding wild-type mice (akt2(+/+)). Transporter protein abundance was determined using Western blotting and phosphate transport by (32)P uptake into brush border membrane vesicles. RESULTS: The phosphate-induced current in NaPi-IIa-expressing Xenopus oocytes was significantly increased by the coexpression of Akt/PKB. Phosphate excretion [micromol per 24 h per g BW] was higher by 91% in akt2(-/-) than in akt2(+/+) mice. The phosphaturia of akt2(-/-) mice occurred despite normal transport activity and expression of the renal phosphate transporters NaPi-IIa, NaPi-IIc and Pit2 in the brush border membrane, a significantly decreased plasma PTH concentration (by 46%) and a significantly enhanced plasma 1,25-dihydroxyvitamin D(3) concentration (by 46%). Moreover, fractional renal Ca(2+) excretion was significantly enhanced (by 53%) and bone density significantly reduced (by 11%) in akt2(-/-) mice. CONCLUSIONS: Akt2/PKBbeta plays a role in the acute regulation of renal phosphate transport and thus contributes to the maintenance of phosphate balance and adequate mineralization of bone.

Determination of the newer quinolones levofloxacin and moxifloxacin in plasma by high-performance liquid chromatography with fluorescence detection.

A simple, accurate, sensitive, and precise reversed-phase (RP) high-performance liquid chromatographic (HPLC) method with fluorescence detection allowing the sensitive and specific quantitation of the newer fluoroquinolones levofloxacin and moxifloxacin is described. Moxifloxacin is used as the internal standard for the determination of levofloxacin and vice versa. A single-step liquid-liquid extraction from human plasma is sufficient for both quinolones. The method is linear from 0.1 to 15 microg/mL and 0.2 to 7 microg/mL for levofloxacin and moxifloxacin, respectively, covering the clinically relevant plasma concentration range. The limits of quantitation are 0.05 microg/mL (levofloxacin) and 0.2 microg/mL (moxifloxacin). The method is successfully applied to plasma drug level monitoring in a volunteer receiving single therapeutic doses of levofloxacin or moxifloxacin at two different occasions.

Ossifying fibromyxoid tumour of soft parts, with focus on unusual clinicopathological features.

AIMS: Ossifying fibromyxoid tumour is a rare lesion that generally occurs in the soft tissues of proximal limbs/girdle, or head and neck. Histologically, it usually consists of bland, mitotically inactive, S100+ cells in a fibromyxoid matrix with a characteristic peripheral ossification. However, we present two cases that deviated from this pattern. MATERIAL AND METHODS: One tumour, which was removed from the axilla of a 55-year-old female, was unusual in its large size (120 mm in diameter) and in its restriction of bone formation to its central zones. The other tumour, which occurred in a 62-year-old female, was remarkable in its acral location on the hand and high mitotic activity (four mitoses per high-power field). These features caused concern and follow-up of the patients was recommended. So far there have been no recurrences (25 and 18 months after surgery, respectively). An additional previously undescribed feature was the presence of fibronexus-like structures by electron microscopy in the second case. However, a myofibroblastic phenotype was not supported by the immunohistochemical findings. CONCLUSION: Though a distinct entity, ossifying fibromyxoid tumour may exhibit a wider clinicopathological spectrum than generally recognized.

Use of an ex vivo ATP luminescence assay to direct chemotherapy for recurrent ovarian cancer.

Chemotherapy for recurrent ovarian carcinoma (ROC) produces response rates of 10-80% depending on the prevalence of platinum resistance. Most patients relapse within 1 year and median progression-free survival (PFS) is generally no more than 6 months. Previous pretherapeutic chemosensitivity assays mostly failed to improve the outcome of patients with ROC. Newly developed ATP assays show promising retrospective correlation with clinical outcome. We report here the first results of ATP assay-directed chemotherapy in patients with ROC. Therapy was selected by the ATP tumor chemosensitivity assay (ATP-TCA) in a prospective open-label pilot trial for ROC. Objective response rate (ORR), PFS and overall survival (OAS) of the first 25 evaluable patients were retrospectively compared with those of 30 others having similar characteristics who were treated empirically within the same period. The actuarial median observation times were 80 weeks for the ATP-TCA group and 83.5 weeks for the control group, respectively. In the control group, a 37% ORR [two complete responses (CR) and nine partial responses (PR)] was followed by a median PFS of 20 weeks and a median OAS of 69 weeks, mainly related to the use of single-agent chemotherapy. The ORR in the ATP-TCA group was 64% (eight CR and eight PR) (p=0.04) with the majority of responses (11 of 16) achieved with novel combinations. The median PFS in this group was 50 weeks (p=0.003) and the median OAS was 97 weeks (p=0.145). Survival of responding patients was similar in both groups. Chemotherapy guided by the ATP-TCA produced a greater benefit with regard to both ORR and PFS in platinum-refractory patients. ATP-TCA-directed chemotherapy for ROC compares favorably with chemotherapy chosen by a clinician and often leads to the choice of novel drug combinations. These promising results now warrant confirmation by prospective randomized trials.

Infrared absorbances of protein side chains.

The spectral parameters of amino acid residue side chain and peptide bond absorptions in the region 1800-1440 cm-1 have been obtained by using an inverse matrix method applied to the infrared spectra of 42 amino acids, dipeptides, and higher peptides in aqueous solution. In addition the pH-dependent extinction coefficients of the amino acid and peptide COO-/NH3+ end groups were derived. It is shown that the secondary structure prediction accuracy of proteins by multivariate data analysis methods increases slightly, if the side chain absorbances of the residues asparagine, glutamine, aspartic acid, glutamic acid, arginine, tyrosine, and lysine are subtracted from the amide I and amide II region.

Adenovirus-induced liver necrosis in a case of AIDS.

Adenovirus-induced liver necrosis is rare. Because the era of AIDS (acquired immunodeficiency syndrome) this entity was seen predominantly in infants suffering from inborn immunodeficiency syndromes or from iatrogenic immunosuppression because of bone marrow or liver transplantation. Here, we report a case of a 30-year-old woman with AIDS who developed fever and rapidly progressing liver failure. A frozen section from a needle biopsy of the liver allowed a quick diagnosis of viral liver necrosis. The light-microscopic and electron microscopic aspects were typical of adenovirus infection and should be known to the surgical pathologist. The diagnosis was confirmed by immunohistochemistry and DNA hybridization analysis.

Tamm-Horsfall glycoprotein: role in inhibition and promotion of renal calcium oxalate stone formation studied with Fourier-transform infrared spectroscopy.

Tamm-Horsfall glycoprotein (THP) from healthy probands inhibits the precipitation of calcium oxalate, whereas THP from individuals who repeatedly develop calcium oxalate stones has no effect or even promotes precipitation. Using Fourier-transform infrared spectroscopy, we found a structural differentiation between these functionally different THPs: a decisive difference in sialic acid content. Quantitative analysis for sialic acid showed the same results. THP from healthy probands had a high sialic acid content (51 +/- 9 g/kg), whereas THP from recurrent stone formers had a decreased sialic acid content (21 +/- 4 g/kg). This explains the dual role of THP in the precipitation of calcium oxalate and the formation of renal stones and shows the importance of glycosylation in the function of this glycoprotein.

New monoclonal antibody (23D12) recognizing three different V gamma elements of the human gamma delta T cell receptor. 23D12+ cells comprise a major subpopulation of gamma delta T cells in postnatal thymus.

The gamma delta TCR is expressed on 1 to 5% of CD3+ human peripheral blood T lymphocytes. The majority of peripheral blood gamma delta T cells expresses V gamma 9 paired with V delta 2; this subset strongly responds to certain microbial ligands. Other gamma delta T cell subsets with unknown Ag specificity expressing different V gamma elements are present in peripheral blood and lymphoid tissue. We describe a new anti-human V gamma mAb termed 23D12 with unusual specificity. As revealed by analysis of a large number of T cell clones and transfectants expressing molecularly well-defined gamma delta TCR, mAb 23D12 recognized several, but not all, members of the human V gamma 1 family, specifically V gamma 2, V gamma 3, and V gamma 4 but not V gamma 5 or V gamma 8. In combination with available mAb against V gamma 4, mAb 23D12 was used to identify V gamma 2- or V gamma 3-bearing cells. On average, 23D12+ cells accounted for 18% of peripheral blood gamma delta T cells and 56% of postnatal gamma delta thymocytes. In combination with anti-V gamma 9 mAb, mAb 23D12 23D12 identified gamma delta cells expressing V elements other than V gamma 2, V gamma 3, V gamma 4, or V gamma 9. Such cells are detectable in peripheral blood and postnatal thymus. Using mAb 23D12, we also confirmed the appearance of two distinct TCR gamma-chains on the surface of some gamma delta T cells.

Thermodynamic parameters of cooperative helix-to-coil transitions from synthetic A-U-rich oligoribonucleotides up to fourteen basepairs.

Heat induced helix-to-coil transitions are studied in the form of ultraviolet-hypochromicity profiles by absorbance spectroscopy, and delta Cp-curves by differential scanning calorimetry of self-complementary ribonucleotides. The results are analyzed and compared. Van 't Hoff transition enthalpies derived by UV-experiments incorporating concentration variations are found to differ from six-parameter and two-parameter Marquardt-fits on the melting profiles. A measure for the maximum number of nucleotides in intermediate states is obtained from a statistical deconvolution. It yields a range from 12.5% for the shortest nucleotide up to 31.5% for r(UA)7. Model independent calorimetric data are reported. A limit for intra-molecular loop-formation preference is reached by rG(UA)6C within this sequence.

Thermodynamics of double- and triple-helical aggregates formed by self-complementary oligoribonucleotides of the type rAxUy.

The thermal denaturation of a series of oligoribonucleotides of the form rAxUy (x = 5 or 7 and y = 3-11) has been characterized by means of IR spectroscopy, UV spectroscopy, and DSC. IR spectra proved the occurrence of double- and triple-helical regions at various contents of uracil residues in the nucleotide. From DSC measurements transition enthalpies, entropies, and free enthalpies were derived. The effect of fraying in terminal base pairs of symmetrical nucleotides (x = y) was quantified. Thermodynamic excess parameters due to dangling ends (5'A and 3'U), terminal AU base pairs, and UAU base triplets were obtained by comparing DSC results from different nucleotides. Empirical values for contributions of base stacking and pairing to the stability of terminal AU base pairs have been estimated: for nucleotides under study with a high degree of fraying at the ends of the helix the major stabilization effect comes from base stacking. The size of the cooperative unit lambda in most nucleotides under study is larger than 1; i.e., in these cases intermolecular cooperation takes place. Through deconvolution of DSC data maximum populations of intermediate states FI,max were obtained. On the basis of these results all nucleotides under study were proved to melt in multistate manner. FI,max increases with the number of base pairs, decreases through dangling ends, and shows approximately constant values for triple-helical aggregates of the series rA5Uy as well as rA7Uy.

A thermodynamic study on rA7U7.

Ultraviolet absorbance spectroscopy and differential scanning calorimetry were employed to study the heat-induced helix-to-coil transition of the oligoribonucleotide rA7U7. The analysis of concentration-dependent ultraviolet 'melting' profiles was used to derive the van't Hoff transition enthalpy delta HUVvH (-458 kJ/mol cooperative unit). From the DSC data we calculated the calorimetric transition enthalpy delta Hcal (-412.6 kJ/mol duplex) as well as delta HcalvH (-447.9 kJ/mol cooperative unit). For the size of the cooperative unit we obtained lambda approximately 1. In contrast to this result, by means of statistical numerical deconvolution we show that intermediate states are significantly populated; at the maximum the fraction of these states reaches 25.4% of the total population. Therefore, this DSC-deconvolution technique offers a more appropriate way to register amounts of populated intermediate states which are not sufficient to obtain a value of lambda which is essentially lower than unity.

A comparative calorimetric study on tRNA unfolding.

The heat effects involved in thermal unfolding of five tRNAs with different primary structures have been determined by direct differential scanning microcalorimetry. The overall molar values of the transition enthalpy (delta Ht) are 1150 kJ/mol for tRNA Lys2 (yeast), 1250 kJ/mol for tRNA Phe (yeast), 1350 kJ/mol for tRNA Val (yeast), 1490 kJ/mol for tRNA Val (E. coli) and 1630 kJ/mol for tRNA Tyr (E. coli). The tRNAs differ in their melting behaviour as can be shown by a comparison of the calorimetric curves. The calorimetrically measured delta Ht values are about 350 kJ/mol higher than the transition enthalpy values for the cloverleaf arrangement, which were estimated using the known parameters for G.C and A.U base pairs.

Determination of base pairing in yeast 5S and 5.8S RNA infrared spectroscopy.

Infrared Spectroscopy was used to determine the numbers of base pairs for yeast 5S RNA and 5.8S RNA. The spectra were recorded at 20 degrees C and 50 degrees C, where tertiary interactions are assumed to be of less importance. It may be concluded that the structure of both RNAs is highly ordered and that there are large contributions of tertiary interactions. The results are compared with data derived from structural models that were proposed in the literature as well as with data previously published for prokaryotic 5S RNAs.

Demonstration of G . U wobble base pairs by Raman and IR spectroscopy.

When guanine and uracil form hydrogen bonds in the pairing scheme first proposed by Crick one would expect that poly(A,G) will form an unperturbed double helix with poly U at room temperature in a dilute electrolyte solution (0.1 M NaCl). We have demonstrated by Raman- and IR-spectroscopy that the secondary structure of poly(A.G) . poly U is very similar to the structure of poly A . poly U; only the thermal stability of the double helix seems slightly lower than the stability of poly A . poly U, whereas the average helix length is unaffected by the dispersed G . U base pairs. From our input ratio of guanine and adenine we estimate that about every fourth base pair is a wobble pair.