Crystallization and stereocomplexation behavior of poly(D- and L-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) block copolymers

The thermal properties, crystallization, and morphology of amphiphilic poly(D-lactide)-b-poly(N,N-dimethylamino- 2-ethyl methacrylate) (PDLA-b-PDMAEMA) and poly (L-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) (PLLA-b-PDMAEMA) copolymers were studied and compared to those of the corresponding poly(lactide) homopolymers. Additionally, stereocomplexation of these copolymers was studied. The crystallization kinetics of the PLA blocks was retarded by the presence of the PDMAEMA block. The studied copolymers were found to be miscible in the melt and the glassy state. The Avrami theory was able to predict the entire crystallization range of the PLA isothermal overall crystallization. The melting points of PLDA/PLLA and PLA/PLA-b-PDMAEMA stereocomplexes were higher than those formed by copolymer mixtures. This indicates that the PDMAEMA block is influencing the stability of the stereocomplex structures. For the low molecular weight samples, the stereocomplexes particles exhibited a conventional disk-shape structure and, for high molecular weight samples, the particles displayed unusual star-like shape morphology.

Guanine specific binding at a DNA junction formed by d[CG(5-BrU)ACG]2 with a topoisomerase poison in the presence of Co2+Ions†,‡

The structure of the duplex d[CG(5-BrU)ACG]2 bound to 9-bromophenazine-4-carboxamide has been solved through MAD phasing at 2.0 Å resolution. It shows an unexpected and previously unreported intercalation cavity stabilized by the drug and novel binding modes of Co2+ ions at certain guanine N7 sites. For the intercalation cavity the terminal cytosine is rotated to pair with the guanine of a symmetry-related duplex to create a pseudo-Holliday junction geometry, with two such cavities linked through the minor groove interactions of the N2/N3 guanine sites at an angle of 40°, creating a quadruplex-like structure. The mode of binding of the drug is shown to be disordered, with the major conformations showing the side chain bound to the N7 position of adjacent guanines. The other end of the duplex exhibits a terminal base fraying in the presence of Co2+ ions linking symmetry-related guanines, causing the helices to intertwine through the minor groove. The stabilization of the structure by the intercalating drug shows that this class of compound may bind to DNA junctions as well as duplex DNA or to strand-nicked DNA (‘hemi-intercalated'), as in the cleavable complex. This suggests a structural basis for the dual poisoning of topoisomerase I and II enzymes by this family of drugs.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Is a lower dose of vitamin D supplementation enough to increase 25(OH)D status in a sunny country?

Calcium and vitamin D are essential nutrients for bone metabolism Vitamin D can either be obtained from dietary sources or cutaneous synthesis. The study was conducted in subtropic weather; therefore, some might believe that the levels of solar radiation would be sufficient in this area. To evaluate calcium and vitamin D supplementation in postmenopausal women with osteoporosis living in a sunny country. A 3-month controlled clinical trial with 64 postmenopausal women with osteoporosis, mean age 62 +/- A 8 years. They were randomly assigned to either the supplement group, who received 1,200 mg of calcium carbonate and 400 IU (10 mu g) of vitamin D(3,) or the control group. Dietary intake assessment was performed, bone mineral density and body composition were measured, and biochemical markers of bone metabolism were analyzed. Considering all participants at baseline, serum vitamin D was under 75 nmol/l in 91.4% of the participants. The concentration of serum 25(OH)D increased significantly (p = 0.023) after 3 months of supplementation from 46.67 +/- A 13.97 to 59.47 +/- A 17.50 nmol/l. However, the dose given was limited in effect, and 86.2% of the supplement group did not reach optimal levels of 25(OH)D. Parathyroid hormone was elevated in 22.4% of the study group. After the intervention period, mean parathyroid hormone tended to decrease in the supplement group (p = 0.063). The dose given (400 IU/day) was not enough to achieve 25(OH)D concentration, considered optimal for bone health.

Projectile breakup dynamics for (6)Li+(59)Co: Kinematical analysis of alpha-d coincidences

A study of the kinematics of the alpha-d coincidences in the (6)Li + (59)Co system at a bombarding energy of E(lab) = 29.6MeV is presented. With exclusive measurements performed over different angular intervals it is possible to identify the respective contributions of the sequential and direct projectile breakup components. The angular distributions of both breakup components are fairly well described by the Continuum-Discretized Coupled-Channels framework (CDCC). Furthermore, a careful analysis of these processes using a semiclassical approach provides information on both their lifetime and their distance of occurrence with respect to the target. Breakup to the low-lying (near-threshold) continuum is delayed, and happens at large internuclear distances. This suggests that the influence of the projectile breakup on the complete fusion process can be related essentially to the direct breakup to the (6)Li high-lying continuum spectrum.

Perfect Simulation of a Coupling Achieving the (d)over-bar-distance Between Ordered Pairs of Binary Chains of Infinite Order

We explicitly construct a stationary coupling attaining Ornstein`s (d) over bar -distance between ordered pairs of binary chains of infinite order. Our main tool is a representation of the transition probabilities of the coupled bivariate chain of infinite order as a countable mixture of Markov transition probabilities of increasing order. Under suitable conditions on the loss of memory of the chains, this representation implies that the coupled chain can be represented as a concatenation of i.i.d. sequences of bivariate finite random strings of symbols. The perfect simulation algorithm is based on the fact that we can identify the first regeneration point to the left of the origin almost surely.

Prevention of bacterial translocation using β-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats

To investigate the role of β-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. Methods: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFα, IL-1β, IL-6, IL-10 were measured by ELISA. Results: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFα, IL-1β and, IL-6, compared to I/R untreated animals. Conclusion: The β-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria

Prevention of bacterial translocation using β-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats

To investigate the role of β-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. Methods: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFα, IL-1β, IL-6, IL-10 were measured by ELISA. Results: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFα, IL-1β and, IL-6, compared to I/R untreated animals. Conclusion: The β-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria

3-D reconstruction by extended depth-of-field in failure analysis - Case study I: Qualitative fractographic investigation of fractured bolts in a partial valve

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Response surface optimization of D(-)-lactic acid production by Lactobacillus SMI8 using corn steep liquor and yeast autolysate as an alternative nitrogen source

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structural basis for metal ion coordination and the catalytic mechanism of sphingomyelinases D

Sphingomyelinases D (SMases D) from Loxosceles spider venom are the principal toxins responsible for the manifestation of dermonecrosis, intravascular hemolysis, and acute renal failure, which can result in death. These enzymes catalyze the hydrolysis of sphingomyelin, resulting in the formation of ceramide 1-phosphate and choline or the hydrolysis of lysophosphatidyl choline, generating the lipid mediator lysophosphatidic acid. This report represents the first crystal structure of a member of the sphingomyelinase D family from Loxosceles laeta (SMase I), which has been determined at 1.75-angstrom resolution using the quick cryo-soaking technique and phases obtained from a single iodine derivative and data collected from a conventional rotating anode x-ray source. SMase I folds as an (alpha/beta)(8) barrel, the interfacial and catalytic sites encompass hydrophobic loops and a negatively charged surface. Substrate binding and/or the transition state are stabilized by a Mg2+ ion, which is coordinated by Glu(32), Asp(34), Asp(91), and solvent molecules. In the proposed acid base catalytic mechanism, His(12) and His(47) play key roles and are supported by a network of hydrogen bonds between Asp(34), Asp(52), Trp(230), Asp(233), and Asn(252).

Measurement of B-d mixing using opposite-side flavor tagging

We report on a measurement of the B-d(0) mixing frequency and the calibration of an opposite-side flavor tagger in the D0 experiment. Various properties associated with the b quark on the opposite side of the reconstructed B meson are combined using a likelihood-ratio method into a single variable with enhanced tagging power. Its performance is tested with data, using a large sample of reconstructed semileptonic B ->mu(DX)-X-0 and B ->mu(DX)-X-* decays, corresponding to an integrated luminosity of approximately 1 fb(-1). The events are divided into groups depending on the value of the combined tagging variable, and an independent analysis is performed in each group. Combining the results of these analyses, the overall effective tagging power is found to be epsilon D-2=(2.48 +/- 0.21(-0.06)(+0.08))%. The measured B-d(0) mixing frequency Delta m(d)=0.506 +/- 0.020(stat)+/- 0.016(syst) ps(-1) is in good agreement with the world average value.

Stability analysis of the D-dimensional nonlinear Schrodinger equation with trap and two- and three-body interactions

Considering the static solutions of the D-dimensional nonlinear Schrodinger equation with trap and attractive two-body interactions, the existence of stable solutions is limited to a maximum critical number of particles, when D greater than or equal to 2. In case D = 2, we compare the variational approach with the exact numerical calculations. We show that, the addition of a positive three-body interaction allows stable solutions beyond the critical number. In this case, we also introduce a dynamical analysis of the conditions for the collapse. (C) 2000 Published by Elsevier B.V. B.V. All rights reserved.

Use of vitamin D to reduce lameness in broilers reared in harsh environments

In tropical poultry-producing countries, poultry houses usually have little environmental control. This study investigated the effect of dietary vitamin D on the incidence of leg abnormalities of a fast-growing broiler strain reared under harsh conditions. In this study, 300 one-day-old male broilers were distributed in two treatments with three replicates of 50 birds each. One group was fed a placebo and the other group was fed 25-hydroxycholecalciferol (25-OH-D3) in a soluble form. The environmental variables were weekly recorded during until birds were 49 days old. Birds were weekly gait scored, and their walking speed and vertical force while walking were assessed. Post-mortem examination was performed and skeletal lesions were assessed. Control birds presented more leg problems than those that ingested 25-OH-D3. These results suggest that dietary vitamin D is effective in decreasing the severity of lameness by reducing tibial dyschondroplasia and other leg abnormalities.

Structure, genomic DNA typing, and kinetic characterization of the D allozyme of placental alkaline phosphatase (PLAP/ALPP)

The D allozyme of placental alkaline phosphatase (PLAP) displays enzymatic properties at variance with those of the common PLAP allozymes. We have deduced the amino acid sequence of the PLAP D allele by PCR cloning of its gene, ALPP Two coding substitutions were found in comparison With the cDNA of the common PLAP F allele, i.e., 692C>G and 1352A>G, which translate into a P209R and E429G substitution. A single nucleotide primer extension (SNuPE) assay was developed using PCR primers that enable the amplification of a 1.9 kb PLAP fragment. Extension primers were then used on this PCR fragment to detect the 692C>G and 1352A>G substitution. The SNuPE assay on these two nucleotide substitutions enabled us to distinguish the PLAP F and D alleles from the PLAP S/I alleles. Functional studies on the D allozyme were made possible by constructing and expressing a PLAP D cDNA, i.e., [Arg209, Gly429] PLAP, into wildtype Chinese hamster ovary cells. We determined the k(cat) and K-m, of the PLAP S, F. and D allozymes using the non,physiological substrate p-nitrophenylphosphate at an optimal pH (9.8) as well as two physiological substrates, i.e., pyridoxal-5'-phosphate and inorganic pyrophosphate at physiological pH (7.5). We found that the biochemical properties of the D allozyme of PLAP are significantly different from those of the common PLAP allozymes. These biochemical findings suggest that a suboptimal enzymatic function by the PLAP D allozyme may be the basis for the apparent negative selective pressure of the PLAP D allele. The development of the SNuPE assay will enable us to test the hypothesis that the PLAP D allele is subjected to intrauterine selection by examining genomic DNA from statistically informative population samples. Hum Mutat 19:258-267, 2002. (C) 2002 Wiley-Liss, Inc.