The influence of water hardness perturbations on bubble departure dynamics.

The influence of small changes to water hardness on the nonlinear behaviour of liquid penetration into a capillary and the resulting air pressure fluctuations during air bubble formation are examined in this paper. Experiments were undertaken in which bubbles were generated both in water having a surface tensile force of σ = 72.2 mN/m and in an aqueous solution of calcium carbonate having a surface tensile force of σ = 75.4 mN/m, each contained in a glass capillary with an internal diameter of 1 mm. It is shown that both the maximum value of liquid penetration into the capillary and bubble growth time are affected by perturbations to the water hardness. The time it takes for the bubble to depart the capillary was estimated using the following nonlinear data analysis methods: time delay (τ), attractor reconstructions, correlation dimension (D), and largest Lyapunov exponent (λ). All estimates demonstrate that the pressure fluctuations in the c-c aqueous solutions and extent of liquid solution penetration into the capillary during the time between subsequent bubble departures behave chaotically. Furthermore, this work demonstrates that the dynamics of bubble formation along with the bubble waiting time are very sensitive to small perturbation in the physical properties of the liquid, and this sensitivity has a significant effect on the observed chaotic behaviour.

Procedures for risk-stratification of lung cancer using buccal nanocytology.

Lung cancer is the leading cause of cancer deaths in the U.S. with survival dramatically depending on stage at diagnosis. We had earlier reported that nanocytology of buccal cells can accurately risk-stratify smokers for the presence of early and late-stage lung cancer. To translate the technique into clinical practice, standardization of operating procedures is necessary to consistently yield precise and repeatable results. Here, we develop and validate simple, robust, and easily implementable procedures for specimen collection, processing, etc. in addition to a commercially-viable instrument prototype. Results of this work enable translation of the technology from academic lab to physicians' office.

How acoustic cavitation can improve adhesion.

In general, ultrasound is commonly used at low power level for non-destructive testing (NDT) and detection of delaminations in adhesive bonded structures. The present paper instead presents an approach where power ultrasound is used to improve interface formation prior to the bonding process and to ensure the quality of adhesive bonds by using acoustic cavitation in the liquid adhesive. Results from high-speed videos, rheological and thermal measurements and destructive testing of adhesive bonds with contaminated surfaces are presented and discussed. Power ultrasound can be used in general to improve adhesion and significantly to improve contamination tolerance and robustness of adhesive bonding processes.

Helicobacter pylori, non-steroidal anti-inflammatory drugs and smoking in risk pattern of gastroduodenal ulcers.

BACKGROUND: Helicobacter pylori, NSAID and cigarette smoking are major risk factors for gastroduodenal ulcers. However, the results of studies on the interaction between these factors on ulcerogenesis are controversial. This study was designed to examine the association between gastroduodenal ulcers and H. pylori infection, NSAID use, smoking and age. METHODS: 5967 dyspeptic patients underwent 13C-urea breath test (UBT) and upper endoscopy, while age and dyspeptic symptoms were reported. RESULTS: Out of 5967 patients, 31.8% were ulcerated; 9.2% had gastric, 17.2% duodenal and 5.4% both gastric and duodenal ulcers. H. pylori was found in 72.5% of gastric ulcer patients, in 83.6% of duodenal ulcer patients, in 76.9% of gastroduodenal ulcer patients and in 64.8% of dyspeptic patients. The gastric, duodenal and gastroduodenal ulcers were related to H. pylori significantly and the respective ORs were: 1.44, 2.77 and 1.81. NSAID alone was used by 6.2%-12.7% of ulcer patients, tending to raise only the risk of gastric ulcer but reducing that of duodenal and gastroduodenal ulcers. The H. pylori prevalence was significantly higher in smokers (76%) than in non-smokers (67%) and the ulcer risk was also significantly higher in smokers than in non-smokers. About 20% of ulcers were 'idiopathic', i.e. without NSAID and H. pylori and the ratio of these ulcers to all ulcers significantly increased during the 5 years of the study. CONCLUSIONS: Based on multivariable logistic regression analysis we conclude that: 1) H. pylori infection, NSAID use, smoking and age play major roles in the pathogenesis of peptic ulcerations; 2) there is a negative interaction between H. pylori and NSAID on duodenal ulcers, suggesting that H. pylori reduces the development of these ulcers in NSAID users, and 3) about 20% of peptic ulcers in the Polish population are unrelated to H. pylori and NSAID use (idiopathic ulcers).

Shear-induced coalescence of emulsified oil drops.

Crude oil droplets, when suspended in water, possess negative surface charges which give rise to double-layer repulsive forces between the drops. According to conventional DLVO theory, the magnitude of this repulsion (based on the measured zeta potential) is more than sufficient to prevent coalescence of the droplets. Indeed, when two such droplets were brought together on direct (i.e., "head-on") approach, coalescence was rarely observed. Upon oblique approach, however, the same droplets were seen to coalesce readily. An oblique encounter must necessarily give rise to lateral relative motion-or shearing-between the droplet surfaces. It is speculated that, if the charge distributions at the droplet surfaces were heterogeneous, lateral shearing would facilitate many encounters between surface patches of different zeta potentials across the intervening water film. If the repulsion across any local region were sufficiently weak to allow formation of an oil bridge across the water film, coalescence of the drops would follow inevitably. With the hypothesis of surface heterogeneity, it is not necessary to invoke any additional colloidal interactions (such as "hydrophobic forces") to account for the observed droplet-droplet coalescence. This finding may have important implications for the underlying mechanisms of emulsion stability in general and the commercial extraction of bitumen from oil sands in particular.

Dynamic and static interactions between bitumen droplets in water.

In the commercial bitumen extraction operation, dynamic and static interaction forces between bitumen drops in water determine the likelihood of desirable bitumen coalescence at different process stages. These dynamic and static forces were measured using colloidal particle scattering and hydrodynamic force balance techniques, respectively. In the former technique, dynamic interactions are studied through droplet-droplet collision trajectory measurement. In the latter technique, the static attractive forces between droplets are determined when a doublet is separated with a known and adjustable hydrodynamic force. The dynamic force measurement implies the presence of rigid chains on bitumen surfaces. The mean chain lengths for deasphalted bitumen at pH 7, whole bitumen at pH 7, and whole bitumen at pH 8.5 are 50, 78, and 41 nm, respectively. However, the static force measurement indicates much shorter mean chain lengths (<9 nm) in these three bitumen systems. Shorter chain length indicates weaker repulsive force. This finding of a much weaker repulsion between bitumen droplets under static conditions has important implications on the commercial bitumen extraction operation.

Effect of thymosin peptides on the chick chorioallantoic membrane angiogenesis model.

The effect of alpha- and beta-thymosin peptides, namely prothymosin alpha (ProT(alpha)), thymosin alpha(1) (T(alpha)1), parathymosin alpha (ParaT(alpha)), thymosin beta(4) (Tbeta4), thymosin beta(10) (Tbeta10), and thymosin beta(9) (Tbeta9), on the angiogenesis process was investigated using the chick chorioallantoic membrane as an in vivo angiogenesis model. The thymosin peptides tested were applied in 10 microl aliquots containing 0.01-4 nmoles of Tbeta4, Tbeta10 or Tbeta9, 0.016-6.66 nmoles of T(alpha)1, 4.1 pmoles-1.66 nmoles of ProT(alpha), and 4.4 pmoles-1.76 nmoles of ParaT(alpha). Phorbol 12-myristate 13-acetate and hydrocortisone were also used as positive and negative control, respectively. Tbeta4, ProT(alpha) and T(alpha)1 were found to enhance angiogenesis, while Tbeta10, Tbeta9 and ParaT(alpha) exhibited an inhibitory effect on the angiogenesis process. When mixtures of Tbeta4 and Tbeta10 containing active amounts of the two peptides at different proportions were applied, the promoting effect of Tbeta4 on angiogenesis was reversed in the presence of increasing concentrations of Tbeta10 and vice versa. The effect of Tbeta10, Tbeta9, ProT(alpha) and ParaT(alpha), in parallel with Tbeta4 and T(alpha)1, on the angiogenesis process was investigated for the first time as far as we know and the results of this study offer more insight into the biological regulatory roles of thymosin peptides, and provide helpful information about their therapeutic potential. Whether these agents could be used either as inhibitors of angiogenesis in disease states where uncontrolled angiogenesis is involved, e.g. in carcinogenesis, or as angiogenesis promoters that could be useful in wound healing, fracture repair, peptic ulcers etc., remains to be further studied.

Secondary structure of prothymosin alpha evidenced for conformational transitions induced by changes in temperature and concentration of n-dodecyltrimethylammonium bromide.

Conformational changes of prothymosin alpha (ProTalpha) induced by changes in temperature and concentration of the denaturant n-dodecyltrimethylammonium bromide (C12TAB) were studied by difference spectroscopy. The conformational transition of ProTalpha by C12TAB was followed as a function of denaturant concentration by absorbance measurements at 230 nm and the data were analyzed to obtain the Gibbs energy of the transition in water (deltaG0(w)) and in a hydrophobic environment (deltaG0(hc)) for saturated protein-surfactant complexes. The value of deltaG0(w) was 6.38 kJ mol(-1) and that for deltaG0(hc), which is not affected by temperature, was -18.62 kJ mol(-1). Changes of absorbance at 230 nm of ProTalpha with temperature can be assumed to resemble a transition in the secondary structure. The parameters characterizing the thermodynamics of unfolding, melting temperature (Tm), enthalpy (deltaHm), entropy (deltaSm) and heat capacity (deltaCp) were determined. The values obtained for Tm, deltaHm, and deltaSm are smaller that those found for other globular proteins; deltaCp was found to be much smaller. These results suggest that ProTalpha exhibits some type of secondary structure under these conditions (10 mM glycine buffer, pH 2.4).

Molecular cloning, characterization and expression of a novel retinal clusterin-like protein cDNA.

A novel gene expressed predominantly in retina, but detected at a conspicuously lower level in retina of canine progressive rod cone degeneration (prcd), has been identified by suppression subtractive hybridization and retinal cDNA library screening. The characterized region of cDNA of the novel gene includes 1017 nucleotides of coding sequence predicted to encode a protein of 338 amino acids (M(r) 39389), 791 nucleotides of 5'-untranslated region (UTR), and 300 nucleotides of 3'-UTR including the poly(A)(+) tail. Multiple transcripts were detected in retina by Northern blot analysis, and a lower level of expression was observed in brain and liver by RT-PCR. The transcript appears to be developmentally regulated with a burst in gene expression at a time period (34 postnatal days) that coincides with the photoreceptor differentiation phase of retinal development. The deduced amino acid sequence from the cDNA of the novel gene has 24% identity and 48% similarity with the multifunctional glycoprotein clusterin. Hence, the putative gene product from the novel transcript has been named clusterin-like protein 1 (CLUL1). The human homologue of CLUL1 cDNA has 84 and 70% identity at the level of nucleotides and amino acids, respectively, with the characterized canine cDNA. The presence of a stretch of 128 amino acids in the putative human CLUL1, not detected in canine CLUL1, suggests alternate splicing events. An STS database search revealed that the human homologue of CLUL1 maps to chromosome 18p, a location not yet reported to harbor an RP locus. Tissue-specific expression of CLUL1 in retina, and its lower abundance in different forms of PRA suggest that this novel gene may represent an as-yet unidentified locus for a retinal disorder.

Preclinical efficacy of thioxanthone SR271425 against transplanted solid tumors of mouse and human origin.

A highly active and broadly active thioxanthone has been identified: N-[[1-[[2-(Diethylamino)ethyl]amino]-7-methoxy-9-oxo-9H-thioxanthen++ +-4-yl] methylformamide (SR271425, BCN326862, WIN71425). In preclinical testing against a variety of subcutaneously growing solid tumors, the following %T/C and Log10 tumor cell kill (LK) values were obtained: Panc-03 T/C = 0, 5/5 cures; Colon-38 (adv. stage) T/C = 0, 3/5 cures, 4.9 LK; Mam-16/C T/C = 0, 3.5 LK; Mam-17/0 T/C = 0, 2.8 LK; Colon-26 T/C = 0, 1/5 cures, 3.2 LK; Colon-51 T/C = 0, 2.7 LK; Panc-02 T/C = 0, 3.1 LK; B16 Melanoma T/C = 13%, 4.0 LK; Squamous Lung-LC12 (adv. stage) T/C = 14%, 4.9 LK; BG-1 human ovarian T/C = 16%, 1.3 LK; WSU-Brl human breast T/C = 25%, 0.8 LK. The agent was modestly active against doxorubicin (Adr)-resistant solid tumors: Mam-17/AdrT/C =23%, 0.8 LK; and Mam-16/C/Adr T/C = 25%, 1.0 LK, but retained substantial activity against a taxol-resistant tumor: Mam-16/C/taxol T/C = 3%, 2.4 LK. SR271425 was highly active against IV implanted leukemias, L1210 6.3 LK and AML1498 5.3 LK. The agent was equally active both by the IV and oral routes of administration, although requiring approximately 30% higher dose by the oral route. Based on its preclinical antitumor profile, it may be appropriate to evaluate SR271425 in clinical trials.

Analysis of Fine Bubble Attachment onto a Solid Surface within the Framework of Classical DLVO Theory.

Fine bubble attachment onto a solid surface in an impinging jet flow was analyzed within the framework of DLVO theory. The effects of hydrodynamic convection, van der Waals (VDW) interaction, electrostatic double-layer (EDL) interaction, and gravitational force on bubble attachment rate (in terms of the Sherwood number) were examined in detail. The analyses showed that due to large Peclet number and gravity number for gas bubbles the behavior of the bubble attachment is significantly different from that of colloidal particle deposition in some aspects. Specifically, it was demonstrated that within a certain range of physicochemical conditions, gas bubbles can attach onto a solid surface despite the existence of repulsive VDW interaction force and the fact that the surfaces of both the bubble and the solid collector carry the same sign of electrostatic potentials. This is attributed to the role played by the short-range attractive asymmetric EDL interaction and the strong hydrodynamic and gravity forces, without any need for the so-called hydrophobic interaction force. In addition, it was also shown that the models derived for the impinging jet system can be used to evaluate transport of fine gas bubbles onto a large particle surface, suggesting that the information extracted from the impinging jet geometry can be applied to the analysis of flotation processes. Copyright 1999 Academic Press.

Strategies for identification of mutations causing hereditary retinal diseases in dogs: evaluation of opsin as a candidate gene.

Progressive retinal atrophy (PRA), like retinitis pigmentosa (RP) in man, represents a clinical classification grouping together a variety of hereditary diseases of the visual cells which have broadly similar clinical characteristics. At least six distinct autosomal recessive and one X-linked retinal disease locus have been identified. As one of the strategies to look for the gene defect causing the different forms of PRA, we are examining first the most promising candidate genes. These include those coding for photoreceptor-specific structural proteins and enzymes of the phototransduction pathway, especially those reported to cause RP. Preeminent among these candidates is the gene for rod opsin, in which multiple causative mutations have been identified in both dominant and recessive forms of RP. In addition, mutations in this gene are also causally associated with congenital stationary night blindness (CSNB) in man. We have used two strategies to examine the rod opsin gene for association with inherited retinal disease in dogs: (1) linkage to determine cosegregation of the disease locus with an intragenic polymorphic marker in the opsin gene in those breeds where suitable informative pedigrees were available; and (2) scanning the coding sequence of the gene in cases where only a limited number of affected or obligate heterozygous samples were available for a breed. We conclude that mutations in the rod opsin gene are not associated with PRA or CSNB in the 11 different dog breeds tested.

Emulsification through Area Contraction.

Emulsification requiring very little input energy can be induced at an oil-water interface that is initially in a state of equilibrium. The process involves destabilization, through contraction, of local interfacial regions. For emulsification to occur, it is necessary for the interfacial structure to have no resistance to surface shearing. Such a mechanism of emulsification may have important implications for the approach to solving emulsion problems in the petroleum industry. Copyright 1999 Academic Press.

Direct ELISA method for the specific determination of prothymosin alpha in human specimens.

An enzyme linked immunosorbent assay, specific for prothymosin alpha (ProT alpha) was developed using an antibody against the synthetic C-terminal peptide ProT alpha[101-109] and isolated bovine ProT alpha for the preparation of standard solutions and immunoplates. Due to the antibody used, the ELISA developed was capable of fully discriminating between ProT alpha, the naturally occuring and partially homologous peptide parathymosin alpha (ParaT alpha) and the peptide thymosin alpha1 (T alpha1), whose sequence is identical to the [1-28] sequence of ProT alpha, and its in vivo occurrence is under question. Moreover, due to its improved sensitivity, the ELISA was capable of directly determining ProT alpha concentration in human serum and tissue extracts, without any pretreatment of the samples. ProT alpha levels were directly measured in sera obtained from 48 apparently healthy individuals and 27 patients with diagnosed breast cancer and found to range from 0.67 to 2.34 microg/ml (mean value 1.27 +/- 0.49 microg/ml) and from 0.47 to 1.74 microg/ml (mean value 1.02 +/- 0.29 microg/ml), respectively. ProT alpha levels were also measured in four breast tumor and adjacent normal breast tissue extracts and found to be elevated in the tumor extracts.

Preclinical antitumor efficacy of analogs of XK469: sodium-(2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]propionate.

A series of quinoxaline analogs of the herbicide Assure was found to have selective cytotoxicity for solid tumors of mice in a disk-diffusion-soft-agar-colony-formation-assay compared to L1210 leukemia. Four agents without selective cytotoxicity and 14 agents with selective cytotoxicity were evaluated in vivo for activity against a solid tumor. The four agents without selective cytotoxicity in the disk-assay were inactive in vivo (T/C > 42%). Thirteen of the fourteen agents with selectivity in the disk-assay were active in vivo (T/C < 42%). Five of the agents had curative activity. These five agents had a halogen (F, Cl, Br) in the 7-position (whereas Assure had a CI in the 6 position). All agents with curative activity were either a carboxylic acid, or a derivative thereof, whereas Assure is the ethyl ester of the carboxylic acid. All other structural features were identical between Assure and the curative agents. Assure had no selective cytotoxicity for solid tumors in the disk-assay, and was devoid of antitumor activity. The analog XK469 is in clinical development.

Interaction of Ionic Species and Fine Solids with a Low Energy Hydrophobic Surface from Contact Angle Measurement.

Interactions of ionic species, (organic and inorganic) precipitates, and fine solids with a low energy hydrophobic surface were examined using a model system of paraffin wax in aqueous solutions. Contact angle measurement was used to evaluate the interactions between paraffin wax and testing variables. No changes in contact angle were observed with various types of metal and metal hydroxyl ions, metal hydroxyl precipitates, fine silica, and alumina powders, suggesting weak or absence of interactions between these species and paraffin wax. At pH <9, the presence of amine reduced the contact angle, but no pH dependence on contact angle was observed for a given amine concentration. A sharp decrease in contact angle was observed at higher pHs, where precipitates of amine molecules formed probably on wax surfaces. In the presence of lauric acid, on the other hand, contact angles reduced at a pH below 8, due to the formation of precipitates, but the reduction was less significant, compared with the reduction by amine precipitates. At high pHs, adding lauric acid did not show any effect on the measured contact angles. The significant effect of fine solids on contact angle was observed only when the solids were made hydrophobic by adsorbed surfactants. The present study further demonstrated that both the thermodynamic criteria and the interactions among substrate/solids/surfactants/metal ions must be considered in identifying the effect of different factors on the wettability of low energy hydrophobic surfaces. Copyright 1998 Academic Press.

Kinetics of Particle Transport to a Solid Surface from an Impinging Jet under Surface and External Force Fields.

Based on the presented model for the impinging jet system, extensive theoretical analysis was made on particle deposition. Complete transport equations with consideration of gravity, van der Waals, and electrical double layer (EDL) interactions, as well as hydrodynamic interactions, were numerically solved. The influences of gravity, van der Waals, and electrical double layer interactions on the particle deposition rates (in terms of the Sherwood number) were presented. The results demonstrate that the asymmetric EDL interaction, which has been ignored in previous treatments, has an impact on the particle deposition rate. It was also found that the Sherwood number is strongly dependent on the characteristics of the particle-collector interaction energy profiles, such as the height of the energy barrier and the depth of the secondary energy minimum. Particularly, the effects of the height of the energy barrier and the depth of the secondary energy minimum on the Sherwood number for different Peclet numbers were discussed. In addition, a simple expression was derived for quantitatively estimating the contributions to the deposition rate due to particle diffusion, migration, and convection. With the aid of calculated particle concentration distributions, this expression can be used to understand the numerical predictions. Copyright 1998 Academic Press.

Prothymosin alpha: a biologically active protein with random coil conformation.

Prothymosin is an acidic protein with an unusual amino acid composition. Though its exact function is not yet known, its high evolutionary conservation and wide tissue distribution suggest an essential biological role. Its physical state, which is controversially discussed in previous publications, was investigated using small-angle X-ray scattering, dynamic light scattering, mass spectrometry, and circular dichroism (CD). Our results unequivocally demonstrate that prothymosin is a monomer under physiological conditions. The protein adopts a random coillike conformation but exhibits persistence of direction and curvature. No regular secondary structure is detectable by CD. The Stokes radius, Rs = 3.07 nm, and the radius of gyration, RG = 4.76 nm, are 1.77 and 3.42 times larger, respectively, than those expected for a compactly folded protein consisting of 109 amino acid residues. A remarkable amount of secondary structure is formed only in the presence of trifluoroethanol at low pH. The finding that a biologically active protein molecule with 109 amino acid residues adopts a random coil conformation under physiological conditions raises the question whether this is a rare or a hitherto-overlooked but widespread phenomenon in the field of macromolecular polypeptides.

Prothymosin alpha 1 modulates lymphokine-activated killer cell activity and IL-2 production by peripheral blood lymphocytes from melanoma patients in vitro.

The effects of prothymosin alpha 1 (Pro alpha 1) on the natural killer (NK), lymphokine (IL-2)-activated killer (LAK) cell activity and the phytohaemagglutinin (PHA)-induced IL-2 secretion of peripheral blood T-lymphocytes (PBL) from 34 malignant melanoma patients of all clinical stages were studied in vitro. On average, melanoma patients showed lower NK and LAK cell activities than healthy donors. In particular, patients with metastases revealed an impaired NK cell activity. However, individuals showed a broad range of LAK cell sensitivity to Pro alpha 1 depending, among other factors, on the disease stage. LAK cell activities were not correlated to tumour stage. Patients' impaired LAK cell activity could be restored by Pro alpha 1. Only patients at stage II (regional metastases) responded to Pro alpha 1. The IL-2 secretion from PBL melanoma and healthy donors did not differ, Pro alpha 1 administration was without any significant effect. However, stage III (distant metastases) PBL expressed significantly lower IL-2 levels, compared to stage I (primary tumours). The highest IL-2 levels was found to be associated with tumour stage II. Pro alpha 1 enhanced the IL-2 secretion from stage I PBL. Therefore Pro alpha 1 administration abrogated the defective LAK cell activity and IL-2 secretion of PBL, mainly from patients at early melanoma stages.

The influence of the thymic preparation thymex-L on deficient antitumor-activity of monocytes from melanoma patients in-vitro.

Recently we demonstrated that, in vitro, prothymosin alpha 1 (ProT alpha), a polypeptide from calf thymus, was able to enhance the deranged tumoristatic activity of peripheral blood monocytes from melanoma patients. Now we report, that the thymic preparation Thymex-L significantly enhanced the level of depressed monocyte activity from 19% to 26%, whereas in normal donor groups no significant change of basal activity (35%) was seen. Although the improvement of median levels of killer cell activity was found to be independent from the disease stage, the Thymex-L effect was only statistically significant in stage I and melanoma patients after chemotherapy. In contrast to ProT alpha, Thymex-L did not further enhance monocyte-mediated cytotoxicity when it was applied in combination with rIFN-gamma. However, after stimulation with rIFN-gamma, the median level of TNF-alpha secretion by melanoma monocytes significantly increased (about 2-fold) when preincubated with Thymex-L. These results indicate that depressed monocyte functions in selected melanoma patients may be partially improved by Thymex-L.