Classification of biodegradable materials using QSAR modelling with uncertainty estimation.

The ability to determine the biodegradability of chemicals without resorting to expensive tests is ecologically and economically desirable. Models based on quantitative structure-activity relations (QSAR) provide some promise in this direction. However, QSAR models in the literature rarely provide uncertainty estimates in more detail than aggregated statistics such as the sensitivity and specificity of the model's predictions. Almost never is there a means of assessing the uncertainty in an individual prediction. Without an uncertainty estimate, it is impossible to assess the trustworthiness of any particular prediction, which leaves the model with a low utility for regulatory purposes. In the present work, a QSAR model with uncertainty estimates is used to predict biodegradability for a set of substances from a publicly available data set. Separation was performed using a partial least squares discriminant analysis model, and the uncertainty was estimated using bootstrapping. The uncertainty prediction allows for confidence intervals to be assigned to any of the model's predictions, allowing for a more complete assessment of the model than would be possible through a traditional statistical analysis. The results presented here are broadly applicable to other areas of modelling as well, because the calculation of the uncertainty will clearly demonstrate where additional tests are needed.

IAN5 polymorphisms are associated with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is frequently associated with lymphopenia. Biobreeding (BB) rat is a typical animal model which develops autoimmune diseases with lymphopenia which results from a frame-shift mutation in the immune-associated nucleotide (IAN) 5 gene. IAN5 is involved in the regulation of T-cell activation and survival. To examine the association of IAN5 gene with SLE, we scrutinised the single nucleotide polymorphisms (SNPs) in the IAN5 gene. We conducted a case-control study where 132 SLE patients, 505 rheumatoid arthritis (RA) patients, and 546 controls were genotyped for four SNPs in the IAN5 gene. Two SNPs (+2071C > T and +2677G > A) were associated with susceptibility to SLE (P = 0.040 and 0.045, respectively), and -4432G > A SNP was associated with the development of leukopenia (P = 0.028) and the requirement of steroid pulse therapy (P = 0.040) in SLE patients. Haplotype analyses showed that Ht1(CTCG) was associated with susceptibility to SLE (P = 0.036), and Ht4(ACCG), Ht5(ACTA) and Ht6(GCCG) were associated with the development of nephritis (P = 0.017, 0.019, 0.022, respectively). In conclusion, the IAN5 polymorphisms were associated with susceptibility to SLE and the development of clinical disease manifestations in a strictly Korean population.

Dissolution kinetics of single crystals of alpha-lactose monohydrate.

The dissolution kinetics of alpha-lactose monohydrate (alphaLM) single crystals were studied by a flow-cell method at different undersaturations. Linear dissolution profiles were obtained as a function of time for all the faces except the (010) face. The dissolution rates, obtained from these profiles, were anisotropic and varied considerably with undersaturation. At low undersaturations (0-2%), the order of dissolution rate was (110) > (100) > (011) = (110) > (010). This order changed with increasing undersaturation (>5%) to (011) >> (100) > (110) > (110) > (010). In alphaLM crystals in which lattice strain was induced by synchrotron X-irradiation, the rates of dissolution of all faces increased with increasing strain. The increase was less significant for the (011) faces than for the remainder. Under this constraint, the (010) face became the fastest dissolving one and the [011]face became the slowest one. The results of all experiments are explained on the basis that although dislocations may act as initiating dissolution centers at very low undersaturations, these sources rapidly give way to two-dimensional nucleation of randomly distributed dissolution sites as the undersaturation is increased. Under these conditions, which better reflect the normal dissolution processes of materials, bulk lattice strain plays the most significant role in defining the dissolution rate. The results show a potential route to the controlled engineering of the dissolution behavior of crystalline materials.

Fracture property studies of paracetamol single crystals using microindentation techniques.

PURPOSE: To study the fracture behavior of the major habit faces of paracetamol single crystals using microindentation techniques and to correlate this with crystal structure and molecular packing. METHODS: Vicker's microindentation techniques were used to measure the hardness and crack lengths. The development of all the major radial cracks was analyzed using the Laugier relationship and fracture toughness values evaluated. RESULTS: Paracetamol single crystals showed severe cracking and fracture around all Vicker's indentations with a limited zone of plastic deformation close to the indent. This is consistent with the material being a highly brittle solid that deforms principally by elastic deformation to fracture rather than by plastic flow. Fracture was associated predominantly with the (010) cleavage plane, but was also observed parallel to other lattice planes including (110), (210) and (100). The cleavage plane (010) had the lowest fracture toughness value, Kc = 0.041MPa m1/2, while the greatest value, Kc = 0.105MPa m1/2 was obtained for the (210) plane. CONCLUSIONS: Paracetamol crystals showed severe cracking and fracture because of the highly brittle nature of the material. The fracture behavior could be explained on the basis of the molecular packing arrangement and the calculated attachment energies across the fracture planes.

The bulk crystallization of alpha-lactose monohydrate from aqueous solution.

The bulk crystallization of alpha-lactose monohydrate from aqueous solution by primary nucleation has been studied under controlled conditions of supersaturation, temperature, and pH. The induction times to nucleation were extremely long compared with those generally observed for other materials, even at the high supersaturations used in the experiment. As a result, it was necessary to stir the supersaturated solution vigorously to induce nucleation in a reasonable but still lengthy working time. Even then, nucleation only occurred to a limited extent, following which growth ceased for 8-10 h before resuming. After this period, growth recommenced but again slowed to a low rate after another 8 h. At this stage, the yield of product was low and in most cases the particles had achieved sizes close to the maximum noted. The yields increased with further crystallization time (22-72 h total from the recommencement of growth) to give, under high initial supersaturation conditions, amounts of product close to the theoretical value. For the most part, however, the particle size did not increase with this later increase in yield, showing only significant changes after the extremely long total crystallization times. It is proposed that these extreme properties result from the formation in solution by mutarotation of the anomer alpha-lactose, which inhibits nucleation as well as its previously observed influence on growth.

Microhardness and dislocation identification studies on paracetamol single crystals.

PURPOSE: To study the mechanical behaviour of paracetamol single crystals. METHODS: Microhardness indentation techniques were used to study the hardness anisotropy of paracetamol. Solvent etching technique was used to define the range of plastic deformation and the orientation of the dislocation lines. The orientation dependence of Knoop hardness on the (001), (110) and (201) surfaces was compared with calculated values of the Effective Resolved Shear Stress (ERSS) for plastic deformation by specific dislocation types. RESULTS: The principal habit faces of single crystals using both Vickers and Knoop indenters showed a range of hardness from 235 to 456 MPa depending on the type of indenter used and its orientation on the surface. Solvent etching of the plastically deformed region of the crystal around the Vickers/Knoop indentations confirmed that the slip plane was (010). ERSS analysis suggested that the deformation occurred by the slip of dislocations of the types (010)[001] and (010)[100]. Crystals doped with 0.08-0.8 w/w% p-acetoxyacetanilide showed hardness values similar to the pure material. CONCLUSIONS: The low number of distinct dislocation slip systems (two) is characteristic of a brittle material and is consistent with the observation that paracetamol will tolerate only deformations of 1 part in 10(6) before fracture.

Crystallization of paracetamol from solution in the presence and absence of impurity.

The bulk crystallization of paracetamol has been examined under controlled conditions in the presence and absence of the additive p-acetoxyacetanilide (PAA), as a function of both supersaturation and additive levels. The induction time to nucleation was found to increase with increase in PAA concentration in solution. The product micro-crystals were characterized for shape and strain/defect content using electron and optical microscopy and X-ray Laue diffraction techniques, respectively. A change in crystal habit of the pure crystals from columnar (dominant [110]) to plate-like (dominant [001]) was observed to occur with an increase in supersaturation level, whilst the addition of PAA invariably led to the development of columnar crystals with an aspect ratio that varied with impurity level and supersaturation. HPLC showed the PAA to be incorporated into the crystals with an average segregation coefficient of 14-18% depending on the supersaturation. The ready incorporation of PAA is attributed to the molecular similarity of this molecule to that of the host material. The incorporation is shown to cause a significant increase in the mosaic spread, implying the development of a significant strain/defect content in the crystals. The influence of the impurity on the time to nucleation is probably due to its effect in blocking the development of the critical nucleus. The potential implications of such variations in morphology and strain content in the design of the physical and chemical properties of the resulting particulates are discussed.

Difference in the distribution pattern of Helicobacter pylori and grade of gastritis in the antrum and in the body between duodenal ulcer and benign gastric ulcer patients.

OBJECTIVES: To investigate the relationship between the Helicobacter pylori (H. pylori) colonization and the grade of gastritis in the antrum and in the body of patients with duodenal ulcer (DU) or benign gastric ulcer (BGU). METHODS: This study was performed in H. pylori-positive 220 DU patients and 180 BGU patients. H. pylori density was evaluated by modified Giemsa staining and CLO test, and gastritis grade was graded by H&E staining in the antrum and in the body. RESULTS: H. pylori grade by Giemsa staining was 1.24 in the antrum and 0.82 in the body for DU group (p < 0.01), and those of BGU group were slightly reversed, 0.83 and 0.87, respectively, but without statistical significance. Similarly H. pylori grade by CLO test was 3.1 in the antrum and 2.8 in the body for DU group (p < 0.01), and those of BGU group 2.3 and 2.6 (p < 0.05), respectively. In contrast, gastritis grade was 1.7 in the antrum and 1.2 in the body for DU group (p < 0.01), and those of BGU group 1.6 and 1.3 (p < 0.01), respectively, similar to those of DU. However, there was a correlation between H. pylori grade and gastritis grade in the antrum and in the body, not only in DU but also in BGU group (p < 0.01). CONCLUSION: In spite of different distribution patterns of H. pylori between DU group and BGU group, gastritis grade of the antrum was significantly higher than that of the body in both DU and BGU. However, gastritis is correlated with H. pylori density not only in DU but also in BGU patients. It looks like the inflammatory reaction to H. pylori is stronger in the antrum than in the body.

Human herpesvirus 8 (KSHV) contamination of peripheral blood and autograft products from multiple myeloma patients.

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), has recently been identified within the bone marrow dendritic cells of multiple myeloma (MM) patients. This virus contains homologues to human cytokines such as IL-6 that could potentially stimulate myeloma cell growth and contribute to disease pathogenesis. Since mobilization chemotherapy may increase circulating dendritic cell numbers, we searched for HHV-8 in peripheral blood mononuclear cells (PBMCs) before and after mobilization chemotherapy given to MM patients. Furthermore, we determined if autograft purging using the CEPRATE SC device would reduce the percentage of HHV-8 infected stem cell products. Only two of the 39 PBMC samples collected prior to mobilization chemotherapy contained PCR detectable virus, yet nine of 37 PBMCs collected on the first day of leukapheresis had detectable HHV-8 (P = 0.016). HHV-8 was more frequently identified in autograft products before vs after Ceprate SC selection (40% vs 15%, P = 0.016). Although the role HHV-8 plays in myeloma pathogenesis remains unclear, these results imply that mobilization chemotherapy increases the numbers of circulating HHV-8-infected dendritic cells within the peripheral blood. In addition, CD34 selection of autograft products in MM patients may reduce the reintroduction of virally infected cells following high-dose chemotherapy. Bone Marrow Transplantation (2000) 25, 153-160.

Wideband holographic three-dimensional ultrasonic imaging of breast and liver phantoms.

Wideband ultrasonic 3-D holography is a unique technique for volumetric imaging with extremely high lateral and depth resolution. The large frequency bandwidth, which is typically 25% to 100%, provides excellent depth resolution. The synthetic aperture provides optimum lateral resolution of one-half wavelength at the pulse center frequency. Wideband impulse holography is a multi-frequency detection and imaging technique where the reflected target's broadband time waveform signals are recorded over a defined aperture. The signals are then decomposed into their discrete frequency components as single frequency holograms, combined in the spatial frequency domain, and reconstructed into a 3-D composite image. The composite image may then be viewed with stereo glasses in 3-D. Recent 3-D holographic images of human female breast and liver phantoms with internal cysts (5 to 10 mm) at 5 MHz illustrate the efficacy of this technique for medical ultrasound 3-D volumetric imaging. A video of the breast and liver phantoms may be presented at the meeting.

Bond strength of younger and older permanent teeth with various etching times.

The purpose of this study was to analyze the tensile bond strength and debonding failure mode in younger and older permanent teeth after etching for 15 and 60 seconds. Bond strength did not change significantly when etching time was increased from 15 to 60 seconds in younger or older permanent teeth. However, regardless of etching time, the bond strength of the older permanent teeth was greater than that of the younger teeth with statistically significant differences. Four types of debonding interface were found; bracket base-resin, within the resin, resin-enamel and enamel detachment. There were no statistically significant differences noted among younger and older permanent teeth with 15 or 60 second etching fracture mode incidence at debondings. Enamel detachment was found only at etching times of 60 seconds. To reduce enamel destruction and save chair time, 15 second etching on either younger or older permanent teeth is suggested.

The effect of pretreatment with fluoride on the tensile strength of orthodontic bonding.

White spot decalcifications and caries occurring adjacent to bonded orthodontic brackets have long been a concern to orthodontists. One procedure suggested to overcome this problem is fluoride treatment prior to bonding. The purpose of this study was to compare the tensile bond strength of orthodontic self-cured resin from Concise on teeth rinsed 4 minutes in 1.23% APF with untreated controls. Measurements were made on an Instron machine. Debonding interfaces were observed with a scanning electron microscope and energy dispersive x-ray spectrometry. Distributions were calculated. The tensile bond strengths of the fluoride-treated teeth and the untreated teeth were not significantly different. The debonding interfaces between resin and bracket base, within the resin itself, and between enamel and resin were similar in the two experimental groups. However, greater enamel detachment was seen within the fluoride pretreatment group. So while fluoride pretreatment does not significantly affect tensile bond strength, it may cause enamel detachment after debonding.