X-ray diffraction, thermal analysis, and Raman scattering study of K2BeF4 and comparation to other member of the (beta)-K2SO4 family with ferroelectric -paraelectric transition

Thermal analysis, powder diffraction, and Raman scattering as a function of the temperature were carried out on K2BeF4. Moreover, the crystal structure was determined at 293 K from powder diffraction. The compound shows a transition from Pna21 to Pnam space group at 921 K with a transition enthalpy of 5 kJ/mol. The transition is assumed to be first order because the compound shows metastability. Structurally and spectroscopically the transition is similar to those observed in (NH4)2SO4, which suggests that the low-temperature phase is ferroelectric. In order to confirm it, the spontaneous polarization has been computed using an ionic model.

Les meules rotatives du site ibérique d'Alorda Park (Calafell, Baix Penedès, Tarragona)

El jaciment iberic d'Alorda Park esta situat a la costa central de Catalunya, a uns 30 km al nordest de Tarragona. El jaciment, l'ocupació del qual es data principalment entre el s. VI i el III aC, ha estat excavat extensament des de 1983. Els treballs d'excavació han lliurat sis metae i disset catilli de molins rotatius, la major part deis quals han estat reutilitzats per a usos secundaris. D' altra banda, cap molí rotatiu ha estat trobat in situ a l'interior d'una casa, de manera que es dedueix que la molta amb aquests instruments era probablement una activitat practicada en instaHacions communals o bé per especialistes. Pel que fa a la funcionalitat d'aquestes peces, les analisis de residus indiquen que eren utilitzades per a la molta de cereal s i, en un sol cas, de faves. Pel que fa a la cronologia, el més antic d'aquests exemplars data de mitjan segle V aC, i la utilització deis molins de rotació continua fins a finals de 1'0- cupació de I'assentament. AIllarg d'aquests tres segles, els molins rotatius d' Alorda Park sofreixen una evolució morfologica els trets essencials de la qual han pogut ser establerts. Els exemplars presentats són morfologicament similars a altres molins iberics de la costa central de Catalunya, pero es diferencien considerablement deis models documentats al País Valencia, a Ullastret i a la Gal'lia meridional. Aquest fet sembla indicar I'existencia de tradicions locals ben caracteritzades, que hauran de ser precisades per les recerques futures. Finalment, cal observar que, segons les analisis de residus, els altres instruments lítics o de triturat descoberts al jaciment (molins de vaivé, morters) han estat utilitzats per a la transformació de materies primeres.

Protein-ligand binding free energy estimation using molecular mechanics and continuum electrostatics. Application to HIV-1 protease inhibitors.

A method is proposed for the estimation of absolute binding free energy of interaction between proteins and ligands. Conformational sampling of the protein-ligand complex is performed by molecular dynamics (MD) in vacuo and the solvent effect is calculated a posteriori by solving the Poisson or the Poisson-Boltzmann equation for selected frames of the trajectory. The binding free energy is written as a linear combination of the buried surface upon complexation, SASbur, the electrostatic interaction energy between the ligand and the protein, Eelec, and the difference of the solvation free energies of the complex and the isolated ligand and protein, deltaGsolv. The method uses the buried surface upon complexation to account for the non-polar contribution to the binding free energy because it is less sensitive to the details of the structure than the van der Waals interaction energy. The parameters of the method are developed for a training set of 16 HIV-1 protease-inhibitor complexes of known 3D structure. A correlation coefficient of 0.91 was obtained with an unsigned mean error of 0.8 kcal/mol. When applied to a set of 25 HIV-1 protease-inhibitor complexes of unknown 3D structures, the method provides a satisfactory correlation between the calculated binding free energy and the experimental pIC5o without reparametrization.

Carnitine deficiency in chronic critical illness.

PURPOSE OF REVIEW: New insight in mitochondrial physiology has highlighted the importance of mitochondrial dysfunction in the metabolic and neuroendocrine changes observed in patients presenting with chronic critical illness. This review highlights specifically the importance of carnitine status in this particular patient population and its impact on beta-oxidation and mitochondrial function. RECENT FINDINGS: The main function of carnitine is long chain fatty acid esterification and transport through the mitochondrial membrane. Carnitine depletion should be suspected in critically ill patients with risk factors such as prolonged continuous renal replacement therapy or chronic parenteral nutrition, and evidence of beta-oxidation impairments such as inappropriate hypertriglyceridemia or hyperlactatemia. When fatty acid oxidation is impaired, acyl-CoAs accumulate and deplete the CoA intramitochondrial pool, hence causing a generalized mitochondrial dysfunction and multiorgan failure, with clinical consequences such as muscle weakness, rhabdomyolysis, cardiomyopathy, arrhythmia or sudden death. In such situations, carnitine plasma levels should be measured along with a complete assessment of plasma amino acid, plasma acylcarnitines and urinary organic acid analysis. Supplementation should be initiated if below normal levels (20 μmol/l) of carnitine are observed. In the absence of current guidelines, we recommend an initial supplementation of 0.5-1 g/day. SUMMARY: Metabolic modifications associated with chronic critical illness are just being explored. Carnitine deficiency in critically ill patients is one aspect of these profound and complex changes associated with prolonged stay in ICU. It is readily measurable in the plasma and can easily be substituted if needed, although guidelines are currently missing.

Analysis of natural variants of the human immunodeficiency virus type 1 gag-pol frameshift stem-loop structure.

Human immunodeficiency virus type 1 uses ribosomal frameshifting for translation of the Gag-Pol polyprotein. Frameshift activities are thought to be tightly regulated. Analysis of gag p1 sequences from 270 plasma virions identified in 64% of the samples the occurrence of polymorphism that could lead to changes in thermodynamic stability of the stem-loop. Expression in Saccharomyces cerevisiae of p1-beta-galactosidase fusion proteins from 10 representative natural stem-loop variants and three laboratory mutant constructs (predicted the thermodynamic stability [Delta G degrees] ranging from -23.0 to -4.3 kcal/mol) identified a reduction in frameshift activity of 13 to 67% compared with constructs with the wild-type stem-loop (Delta G degrees, -23.5 kcal/mol). Viruses carrying stem-loops associated with greater than 60% reductions in frameshift activity presented profound defects in viral replication. In contrast, viruses with stem-loop structures associated with 16 to 42% reductions in frameshift efficiency displayed no significant viral replication deficit.

Swine monoclonal antibodies of high affinity and specificity to carcinoembryonic antigen.

To avoid the exclusive use of rodent monoclonal antibodies (MAbs) in patients for the detection of tumors by immunoscintigraphy and for radioimmunotherapy, swine MAbs were produced that are directed against carcinoembryonic antigen (CEA). Spleen cells from 2 pigs immunized with purified colon carcinoma CEA were fused with a nonsecreting mouse myeloma cell line by conventional methods, except that a particularly long immunization protocol and large amounts of spleen and myeloma cells were used. Of 1,200 growing hybrids tested, 20 were found initially to produce antibodies binding to radiolabeled CEA. Seven stable clones producing anti-CEA MAbs for more than 6 months were derived from these hybrids by repeated subcloning. The pig origin of the seven MAbs was demonstrated in a solid-phase CEA enzyme immunoassay where anti-pig immunoglobin (Ig) antibodies coupled to peroxidase gave a positive reaction while anti-mouse Ig antibodies were entirely negative. All swine MAbs were of the IgG isotype. Three anti-CEA MAbs showed no cross-reactivity with granulocytes, while four others gave various degrees of reactivity with different granulocyte glycoproteins. Competitive binding to CEA performed for two purified swine MAbs showed that they recognized two different epitopes. The affinity constants measured for these two MAbs by Scatchard plot on purified CEA were high (1.2 X 10(9) and 1.2 X 10(10) liter/mol). One of the MAbs was tested in vivo for tumor localization by injection, after radiolabeling, in nude mice bearing human colon carcinoma xenograft. High ratios of tumor to normal tissue were obtained with mean values of 10.5 for intact MAbs and of 26.8 for F(ab')2 fragments of the porcine MAb. The results showed that heterofusion with this particular protocol can be used to produce swine MAbs of high affinity and specificity for a well-defined tumor marker. These reagents may have an important clinical utility, particularly in patients who became sensitized to mouse immunoglobulins.

Associations of serum uric acid and SLC2A9 variant with depressive and anxiety disorders: a population-based study

Background: Limited information exists regarding the association between serum uric acid (SUA) and psychiatric disorders. We explored the relationship between SUA and subtypes of major depressive disorder (MDD) and specific anxiety disorders. Additionally, we examined the association of SLC2A9 rs6855911 variant with anxiety disorders. Methods: We conducted a cross-sectional analysis on 3,716 individuals aged 35-66 years previously selected for the population-based CoLaus survey and who agreed to undergo further psychiatric evaluation. SUA was measured using uricase-PAP method. The French translation of the semi-structured Diagnostic Interview for Genetic Studies was used to establish lifetime and current diagnoses of depression and anxiety disorders according to the DSM-IV criteria. Results: Men reported significantly higher levels of SUA compared to women (357}74 μmol/L vs. 263}64 μmol/L). The prevalence of lifetime and current MDD was 44% and 18% respectively while the corresponding estimates for any anxiety disorders were 18% and 10% respectively. A quadratic hockey-stick shaped curve explained the relationship between SUA and social phobia better than a linear trend. However, with regards to the other specific anxiety disorders and other subtypes of MDD, there was no consistent pattern of association. Further analyses using SLC2A9 rs6855911 variant, known to be strongly associated with SUA, supported the quadratic relationship observed between SUA phenotype and social phobia. Conclusions: A quadratic relationship between SUA and social phobia was observed consistent with a protective effect of moderately elevated SUA on social phobia, which disappears at higher concentrations. Further studies are needed to confirm our observations.

Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial.

BACKGROUND: Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125-200 pM/l is lacking. We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo. METHODS: This multicentre (13 general practices, two nursing homes, and one primary care center in western Switzerland), parallel, randomised, controlled, closed-label, observer-blind trial included 50 patients with serum vitamin B12 levels between 125-200 pM/l who were randomized to receive either oral vitamin B12 (1000 μg daily, N = 26) or placebo (N = 24) for four weeks. The institution's pharmacist used simple randomisation to generate a table and allocate treatments. The primary outcome was the change in serum methylmalonic acid (MMA) levels after one month of treatment. Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels. Blood samples were centralised for analysis and adherence to treatment was verified by an electronic device (MEMS; Aardex Europe, Switzerland). Trial registration: ISRCTN 22063938. RESULTS: Baseline characteristics and adherence to treatment were similar in both groups. After one month, one patient in the placebo group was lost to follow-up. Data were evaluated by intention-to-treat analysis. One month of vitamin B12 treatment (N = 26) lowered serum MMA levels by 0.13 μmol/l (95%CI 0.06-0.19) more than the change observed in the placebo group (N = 23). The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 (95% CI 1.7-6.4). A significant change was observed for the B12 serum level, but not for the homocysteine level, hematocrit, or mean corpuscular volume. After three months without active treatment (at four months), significant differences in MMA levels were no longer detected. CONCLUSIONS: Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency. However, a one-month daily treatment with 1000 μg oral vitamin B12 was not sufficient to normalise the deficiency markers for four months, and treatment had no effect on haematological signs of B12 deficiency.

Crystallization and properties of poly(ethylene terephtalate) copolymers containing 5-tert-butyl isophtalic units

The influence of incorporating 5-tert-butyl isophthalic units (tBI) in the polymer chain of poly(ethylene terephthalate) (PET) on the crystallization behavior, crystal structure, and tensile and gas transport properties of this polyester was evaluated. Random poly(ethyleneterephthalate-co-5-tert-butyl isophthalate) copolyesters (PETtBI) containing between 5 and 40 mol% of tBI units were examined. Isothermal crystallization studies were performed on amorphous glassy films at 120 8C and on molten samples at 200 8C by means of differential scanning calorimetry. Furthermore, the non-isothermal crystallization behavior of the copolyesters was investigated. It was observed that both crystallinity and crystallization rate of the PETtBI copolyesters tend to decrease largely with the comonomeric content, except for the copolymer containing 5 mol% of tBI units, which crystallized faster than PET. Fiber X-ray diffraction patterns of the semicrystalline PETtBI copolyesters proved that they adopt the same triclinic crystal structure as PET with the comonomeric units being excluded from the crystalline phase. Although PETtBI copolyesters became brittle for higher contents in tBI, the tensile modulus and strength of PET were barely affected by copolymerization. The ncorporation of tBI units slightly increased the permeability of PET, but copolymers containing up to 20 mol% of the comonomeric units were still able to present barrier properties.

Physiological responses of two tropical weeds to shade: I. Growth and biomass allocation

Ipomoea asarifolia (Desr.) Roem. & Schultz (Convolvulaceae) and Stachytarpheta cayennensis (Rich) Vahl. (Verbenaceae), two weeds found in pastures and crop areas in Brazilian Amazonia, were grown in controlled environment cabinets under high (800-1000 µmol m-² s-¹) and low (200-350 µmol m-² s-¹) light regimes during a 40-day period. For both species leaf dry mass and leaf area per total plant dry mass, and leaf area per leaf dry mass were higher for low-light plants, whereas root mass per total plant dry mass was higher for high-light plants. High-light S. cayennensis allocated significantly more biomass to reproductive tissue than low-light plants, suggesting a probably lower ability of this species to maintain itself under shaded conditions. Relative growth rate (RGR) in I. asarifolia was initially higher for high-light grown plants and after 20 days started decreasing, becoming similar to low-light plants at the last two harvests (at 30 and 40 days). In S. cayennensis, RGR was also higher for high-light plants; however, this trend was not significant at the first and last harvest dates (10 and 40 days). These results are discussed in relation to their ecological and weed management implications.

Physiological responses of two tropical weeds to shade: II. Leaf gas exchange and nitrogen content

Ipomoea asarifolia (Desr.) Roem. & Schultz (Convolvulaceae) and Stachytarpheta cayennensis (Rich) Vahl. (Verbenaceae), two weeds found in pastures and crop areas in the Brazilian Amazonia, Brazil, were grown in controlled environment cabinets under high (800-1000 µmol m-² s-¹) and low (200-350 µmol m-² s-¹) light regimes during a 40-day period. The objective was to determine the effect of shade on photosynthetic features and leaf nitrogen content of I. asarifolia and S. cayennensis. High-irradiance grown I. asarifolia leaves had significantly higher dark respiration and light saturated rates of photosynthesis than low-irradiance leaves. No significant differences for these traits, between treatments, were observed in S. cayennensis. Low-irradiance leaves of both species displayed higher CO2 assimilation rates under low irradiance. High-irradiance grown leaves of both species had less nitrogen per unit of weight. Low-irradiance S. cayennensis had more nitrogen per unit of leaf area than high-irradiance plants; however, I. asarifolia showed no consistent pattern for this variable through time. For S. cayennensis, leaf nitrogen content and CO2 assimilation were inversely correlated to the amount of biomass allocated to developing reproductive structures. These results are discussed in relation to their ecological and weed management implications.

Liver, gastrointestinal and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: Results from the PRECISION V randomized trial : B-240

Purpose: To evaluate the toxicity focussing on hepatic, gastrointestinal and cardiac parameters following PRECISION TACE with DC Bead? versus conventional transarterial chemoembolization (cTACE) in the treatment of intermediate-stage hepatocellular carcinoma (HCC). Methods and Materials: This prospective, randomized, multicentre study was conducted under best practice trial management and authorized by local institutional review boards. Informed consent was obtained. 212 patients (185 men/27 women; mean: 67 years) were randomized to be treated with DC Beads? or cTACE. The majority of both groups presented in a more advanced stage. Safety was measured by rate of adverse events (South West Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed by means of left ventricular ejection fraction (LVEF) in MRI or echocardiography. The results of the two groups were compared using the chi-square test and Student`s t-test. Results: Mean maximum alanine transaminase increase in the DC Bead group was 50% in the cTACE group (p < 0.001) and 59% for aspartate transaminase (p < 0.001). For bilirubin, mean increase was 5.30±15.13 vs. 13.53±73.89 µmol/L. Concerning gastrointestinal disorders, 120 adverse events (AEs) occurred in 57/93 (61.3%) patients in the DC Bead group vs. 114 in 49/108 (45.4%) in cTACE. Concerning hepatobiliary disorders, serious AEs occurred in 8/93 (8.6%) vs. 11/108 (10.2%) patients. LVEF showed an increase in the DC Bead group by +2.7±10.1 percentage points and a small decrease by -1.5±7.6 in the cTACE group, p=0.018. Conclusion: PRECISION TACE is safe, even in more advanced HCC patients. Serious liver and cardiac toxicity were significantly lower in the DC Bead group.

Boron adsorption in soils from the State of São Paulo, Brazil

Boron adsorption was studied in five representative soils (Rhodic Hapludox, Arenic Paleudalf and three Typic Hapludox) from the State of São Paulo, Brazil. Adsorption was higher in the clayey Oxisols, followed by the Alfisol and the coarser Oxisols. Calcium carbonate promoted an increase in the amount of adsorbed boron in all soils, with the most pronounced effect in the coarser-textured Oxisols. High correlation coefficients were found between adsorbed boron and clay and amorphous aluminum oxide contents and specific surface area (r = 0.79, 0.76 and 0.73, respectively, p < 0.01). Clay content, free aluminum oxide, and hot CaCl2 (0.01 mol L-1)-extracted boron explained 93% of the variation of adsorbed boron. Langmuir and Freundlich isotherms fitted well to the adsorbed data, and highest values for maximum boron adsorption were found in clayey soils, which were significantly correlated with contents of total, free and amorphous iron and aluminum oxides, as well with the physical attributes. Ninety four percent of the variation in the maximum adsorption could be related to the free iron content.

Une cause de cardiomyopathie dilatée chez l'enfant: le déficit primaire en carnitine [A cause of dilated cardiomyopathy in child: primary carnitine deficiency].

AIM: The aim of this case report was to show the importance to research metabolic etiology, especially a carnitine deficiency in dilated cardiomyopathy of children. CASE REPORT: A three years old Togolese child presented muscular hypotonia, dyspnea. Examination showed left galop murmur and systolic murmur 2/6. Chest X-ray showed cardiomegaly (CTI: 0.66), electrocardiogram, a sinusal rythm, left ventricle hypertrophy and T wave abnormalities. Echocardiogram showed a markedly dilated left ventricle with reduced systolic function (EF: 0.43; reference range 0.55-0.80) and moderate mitral regurgitation. The inflammatory signs where negatives. Magnetic resonance imaging don't show signs of ischemic or myocarditis. The levels of free and total plasmatic carnitine decreased: 3μmol/L (N: 18-48μmol/L) and 5μmol/l (N: 29-70μmol/L) respectively. Mutation analysis of the gene SLC22A5 confirms the diagnosis of primary systemic carnitine deficiency. Treatment with oral carnitine was started at 200mg/kg per day. Within three weeks of treatment, we observed the decrease of all symptoms and the left ventricular size and function normalized (EF: 0.62). He has now been on oral carnitine for live. CONCLUSION: Primary carnitine deficiency is a cause of dilated cardiomyopathy in child. It must systematically be suspected when a child presents a primitive cardiomyopathy. The treatment with oral carnitine for live is simple, with excellent prognosis.

Sensitive determination of D-lactic acid and L-lactic acid in urine by high-performance liquid chromatography-tandem mass spectrometry.

D-lactic acid in urine originates mainly from bacterial production in the intestinal tract. Increased D-lactate excretion as observed in patients affected by short bowel syndrome or necrotizing enterocolitis reflects D-lactic overproduction. Therefore, there is a need for a reliable and sensitive method able to detect D-lactic acid even at subclinical elevation levels. A new and highly sensitive method for the simultaneous determination of L- and D-lactic acid by a two-step procedure has been developed. This method is based on the concentration of lactic acid enantiomers from urine by supported liquid extraction followed by high-performance liquid chromatography-tandem mass spectrometry. The separation was achieved by the use of an Astec Chirobiotic? R chiral column under isocratic conditions. The calibration curves were linear over the ranges of 2-400 and 0.5-100 µmol/L respectively for L- and D-lactic acid. The limit of detection of D-lactic acid was 0.125 µmol/L and its limit of quantification was 0.5 µmol/L. The overall accuracy and precision were well within 10% of the nominal values. The developed method is suitable for production of reference values in children and could be applied for accurate routine analysis.