A multiplier method with automatic limitation of penalty growth

This paper presents a multiplier method for solving optimization problems with equality and inequality constraints. The method realizes all the good features that were foreseen by R. Fletcher for this type of algorithm in the past, but which suffers from none of the drawbacks of the earlier attempts.Research sponsored by the National Science Foundation (RANN) Grant ENV76-04264 the National Science Foundation Grant ENG73-08214-A01 and the Sweden-American Foundation.     

On the Number of Lost Customers in Stationary Loss Systems in the Light Traffic Case

For the stationary loss systems M/M/m/K and GI/M/m/K, we study two quantities: the number of lost customers during the time interval (0,t] (the first system only), and the number of lost customers among the first n customers to arrive (both systems). We derive explicit bounds for the total variation distances between the distributions of these quantities and compound Poisson–geometric distributions. The bounds are small in the light traffic case, i.e., when the loss of a customer is a rare event. To prove our results, we show that the studied quantities can be interpreted as accumulated rewards of stationary renewal reward processes, embedded into the queue length process or the process of queue lengths immediately before arrivals of new customers, and apply general results by Erhardsson on compound Poisson approximation for renewal reward processes.     

In vitro contrast-enhanced ultrasound measurements of capillary microcirculation: Comparison between polymer- and phospholipid-shelled microbubbles

The focus of contrast-enhanced ultrasound research has developed beyond visualizing the blood pool and its flow to new areas such as perfusion imaging, drug and gene therapy, and targeted imaging. In this work comparison between the application of polymer- and phospholipid-shelled ultrasound contrast agents (UCAs) for characterization of the capillary microcirculation is reported. All experiments are carried out using a microtube as a vessel phantom. The first set of experiments evaluates the optimal concentration level where backscattered signal from microbubbles depends on concentration linearly. For the polymer-shelled UCAs the optimal concentration level is reached at a value of about 2 × 10⁴ MB/ml, whereas for the phospholipid-shelled UCAs the optimal level is found at about 1 × 10⁵ MB/ml.Despite the fact that the polymer shell occupies 30% of the radius of microbubble, compared to 0.2% of the phospholipid-shelled bubble, approximately 5-fold lower concentration of the polymer UCA is needed for investigation compared to phospholipid-shelled analogues. In the second set of experiments, destruction/replenishment method with varied time intervals ranging from 2 ms to 3 s between destructive and monitoring pulses is employed. The dependence of the peak-to-peak amplitude of backscattered wave versus pulse interval is fitted with an exponential function of the time γ = A(1 − exp(−βt)) where A represents capillary volume and the time constant β represents velocity of the flow. Taking into account that backscattered signal is linearly proportional to the microbubble concentration, for both types of the UCAs it is observed that capillary volume is linearly proportional to the concentration of the microbubbles, but the estimation of the flow velocity is not affected by the change of the concentration. Using the single capillary model, for the phospholipid-shelled UCA a delay of about 0.2-0.3 s in evaluation of the perfusion characteristics is found while polymer-shelled UCA provide response immediately. The latter at the concentration lower than 3.6 × 10⁵ MB/ml have no statistically significant delay (p < 0.01), do not cause any attenuation of the backscattered signal or saturation of the receiving part of the system. In conclusion, these results suggest that the novel polymer-shelled microbubbles have a potential to be used for perfusion evaluation.     

Effect of Heparin,Fucoidan and Other Polysaccharides on Adhesion of Enterohepatic <Emphasis Type="Italic">Helicobacter</Emphasis> Species to Murine Macrophages

Helicobacter species have been isolated and cultured from both the gastric and enterohepatic niches of the gastrointestinal tract and are associated with a wide spectrum of diseases. Some members of the enterohepatic Helicobacter species (EHS), which include Helicobacter bilis, Helicobacter hepaticus and Helicobacter pullorum, are associated with chronic inflammatory and proliferative bowel inflammation, hepatitis and in experimental murine studies with hepatic cancer. The present study aimed to explore if polysulphated polysaccharides can prevent adhesion of EHS to the murine macrophage cell line J774A.1. A competitive binding assay showed that heparin and heparan sulphate at a concentration of 1.25 mg/ml reduced binding of H. hepaticus and H. pullorum to the host cells, but not H. bilis. Of the tested Helicobacter spp, the highest inhibition by heparin was demonstrated for H. pullorum (P < 0.01), the most hydrophilic strain. Partially or completely de-sulphated heparin derivatives lost the ability to inhibit adherence of EHS, indicating the importance of sulphated groups of heparin. The most efficient inhibitor of EHS binding to macrophages was fucoidan, which reduced bacterial adhesion of the three enterohepatic Helicobacter species to a greater extent than heparin, 60–90% inhibition vs 30–70% inhibition by heparin. Identification of receptors that EHS ligands bind to is important for understanding the development of infection and may provide a rational target to prevent infection and therapy.     

Optimization of functions whose values are subject to small errors

In this paper we consider the minimization of a function whose values can only be obtained with an error. For the case when the error has certain statistical properties this problem has been investigated by Kiefer and Wolfowitz (1) and Kushner (2, 3). Kushner has shown that a certain class of algorithms converge to a stationary point with probability one. Here a different approach is used. The error is assumed to have an upper bound and it is shown that a stationary point can be obtained to within a certain accuracy, dependent on the magnitude of the error. Our results are related to works concerning roundoff errors for one dimensional optimization (4) and solution of nonlinear equations (5). The algorithm we use can be regarded as an extension of the methods used in (6), (8) and (9).Supported by: Institutet för tillämpad matematik (Sweden) and the National Science Foundation (USA) under grant MPS 72-04787-a02.     

In vitro synthesis of (1→3)-β-D-glucan (callose) and cellulose by detergent extracts of membranes from cell suspension cultures of hybrid aspen

The aim of this work was to optimize the conditions for in vitro synthesis of (1→3)-β-D-glucan (callose) and cellulose, using detergent extracts of membranes from hybrid aspen (Populus tremula × tremuloides) cells grown as suspension cultures. Callose was the only product synthesized when CHAPS extracts were used as a source of enzyme. The optimal reaction mixture for callose synthesis contained 100 mM Mops buffer pH 7.0, 1 mM UDP-glucose, 8 mM Ca²⁺, and 20 mM cellobiose. The use of digitonin to extract the membrane-bound proteins was required for cellulose synthesis. Yields as high as 50% of the total in vitro products were obtained when cells were harvested in the stationary phase of the growth curve, callose being the other product. The optimal mixture for cellulose synthesis consisted of 100 mM Mops buffer pH 7.0, 1 mM UDP-glucose, 1 mM Ca²⁺, 8 mM Mg²⁺, and 20 mM cellobiose. The in vitroβ-glucans were identified by hydrolysis of radioactive products, using specific enzymes. ¹³C-Nuclear magnetic resonance spectroscopy and transmission electron microscopy were also used for callose characterization. The (1→3)-β-D-glucan systematically had a microfibrillar morphology, but the size and organization of the microfibrils were affected by the nature of the detergent used for enzyme extraction. The discussion of the results is included in a short review of the field that also compares the data obtained with those available in the literature. The results presented show that the hybrid aspen is a promising model for in vitro studies on callose and cellulose synthesis.     

On stationary renewal reward processes where most rewards are zero

We consider a stationary version of a renewal reward process, i.e., a renewal process where a random variable called a reward is associated with each renewal. The rewards are nonnegative and I.I.D., but each reward may depend on the distance to the next renewal. We give an explicit bound for the total variation distance between the distribution of the accumulated reward over the interval (0,L] and a compound Poisson distribution. The bound depends in its simplest form only on the first two joint moments of T and Y (or I{Y > 0}), where T is the distance between successive renewals and Y is the reward. If T and Y are independent, and LE(Y) (or LP(Y > 0)) is bounded or Y binary valued, then the bound is O(E(Y)) as E(Y) → 0 (or O(P(Y > 0)) as P(Y > 0) → 0). To prove our result we generalize a Poisson approximation theorem for point processes by Barbour and Brown, derived using Stein's method and Palm theory, to the case of compound Poisson approximation, and combine this theorem with suitable couplings. Received: 1 March 1999 / Revised version: 2 August 1999 /?Published online: 31 May 2000     

Quantitative comparison of IMAC and TiO<Subscript>2</Subscript> surfaces used in the study of regulated,dynamic protein phosphorylation

Protein phosphorylation regulates many aspects of cellular function, including cell proliferation, migration, and signal transduction. An efficient strategy to isolate phosphopeptides from a pool of unphosphorylated peptides is essential to global characterization using mass spectrometry. We describe an approach employing isotope tagging reagents for relative and absolute quantification (iTRAQ) labeling to compare quantitatively commercial and prototypal immobilized metal affinity chelate (IMAC) and metal oxide resins. Results indicate a prototype iron chelate resin coupled to magnetic beads outperforms either the Ga(3+)-coupled analog, Fe(3+), or Ga(3+)-loaded, iminodiacetic acid (IDA)-coated magnetic particles, Ga(3+)-loaded Captivate beads, Fe(3+)-loaded Poros 20MC, or zirconium-coated ProteoExtract magnetic beads. For example, compared with Poros 20MC, the magnetic metal chelate (MMC) studied here improved phosphopeptide recovery by 20% and exhibited 60% less contamination from unphosphorylated peptides. With respect to efficiency and contamination, MMC performed as well as prototypal magnetic metal oxide-coated (TiO(2)) beads (MMO) or TiO(2) chromatographic spheres, even if the latter were used with 2,5-dihydroxybenzoic acid (DHB) procedures. Thus far, the sensitivity of the new prototypes reaches 50 fmol, which is comparable to TiO(2) spheres. In an exploration of natural proteomes, tryptic (phospho)peptides captured from stable isotopic labeling with amino acids in cell culture (SILAC)-labeled immunocomplexes following EGF-treatment of 5 x 10(7) HeLa cells were sufficient to quantify stimulated response of over 60 proteins and identify 20 specific phosphorylation sites.     

Creation of hollow zeolite architectures by controlled desilication of Al-zoned ZSM-5 crystals

Hollow zeolite architectures on different length scales have been obtained upon controlled desilication of Al-zoned ZSM-5 zeolites in alkaline medium. The hollow ZSM-5 crystals possess a functional Al-rich exterior and a tunable internal porosity and accessibility.     

Bile Enhances Cell Surface Hydrophobicity and Biofilm Formation of Bifidobacteria

Twenty-four human bifidobacterial strains were analysed for cell surface hydrophobicity (CSH) using a salt aggregation test (SAT) and a Congo red binding (CRB) assay. Three strains were selected for a systematic study on the CSH and biofilm formation: Bifidobacterium breve 46, Bifidobacterium animalis ssp. lactis 8:8 and a reference strain B. animalis ssp. lactis JCM 10602. CRB of the B. breve 46 and B. animalis ssp. lactis JCM 10602 was significantly enhanced (P?<?0.05) when grown in deMan–Rogosa–Sharpe cysteine (MRSC) broth supplemented with taurocholic acid (TA) or native porcine bile (PB). An enhanced CSH of the strains grown with PB and gastric mucin correlated with an increased mucin binding and an enhanced biofilm formation in prebiotic oligosaccharide-supplemented cultures. The three strains showed late bile-induced biofilm (72 h) under an anaerobic growth condition, and both B. animalis ssp. lactis strains showed a late bile-induced biofilm formation under aerobic conditions shown by crystal violet staining. These two strains were thus considered to be oxygen tolerant and more robust. Furthermore, enhanced biofilm formation of these robust bifidobacterial strains in the presence of prebiotics may allow for strong colonisation in the gastrointestinal tract when administered to in vivo models as a “synbiotic supplement”.