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Introduction Most kidney diseases are associated with the dysfunction of the glomerular filtration barrier (GFB), which comprises 3 layers, including the glomerular endothelial cells (GEC), the glomerular basement membrane (GBM) [...], Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine.

In autism spectrum disorder (ASD), medical conditions in infancy could be predictive markers for later ASD diagnosis. In this study, electronic medical records of 579 autistic individuals and 1897 matched controls prior to age 2 were analyzed for potential predictive conditions. Using a novel tool, the relative association of each condition in the autistic group was compared to the control group using logistic regressions across medical records. Generalized convulsive epilepsy, nystagmus, lack of normal physiological development, delayed milestones, and strabismus were more likely in those later diagnosed with ASD while perinatal jaundice was less likely to be associated. Lesser-known conditions, such as strabismus and nystagmus, may point to novel predictive co-occurring condition profiles which could improve screening practices for ASD., Author(s): Ekomobong E. Eyoh [sup.1] [sup.10] , Michelle D. Failla [sup.2] , Zachary J. Williams [sup.3] [sup.4] [sup.5] [sup.6] , Kyle L. Schwartz [sup.6] , Laurie E. Cutting [sup.7] [sup.8] [...]

Immunotherapeutic strategies are increasingly important in neuro-oncology, and the elucidation of escape mechanisms that lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing WT and [Pd-1.sup.-/-] mice survived significantly longer than immunodeficient [Pfp.sup.-/-] [Rag2.sup.-/-] mice. While tumors in [Pfp.sup.-/-] [Rag2.sup.-/-] mice were highly polyclonal, immunoedited tumors in WT and [Pd-1.sup.-/-] mice displayed reduced clonality with emergence of immune escape clones. Tumor cells in WT mice were distinguished by an IFN-[gamma]-mediated response signature with upregulation of genes involved in immunosuppression. Tumor-infiltrating stromal cells, which include macrophages/microglia, contributed even more strongly to the immunosuppressive signature than the actual tumor cells. The identified murine immune escape signature was reflected in human patients and correlated with poor survival. In conclusion, immune pressure profoundly shapes the clonal composition and gene regulation in malignant gliomas., Introduction Glioblastoma represents the most frequent aggressive intrinsic brain tumor, and patient outcome remains uniformly fatal despite improved treatment options (1). The current era of glioblastoma therapy is being redefined [...]

This study is a randomized control trial aimed at testing the role of a human-assisted social robot as an intervention mediator in a socio-emotional understanding protocol for children with autism spectrum disorders (ASD). Fourteen children (4-8 years old) were randomly assigned to 10 sessions of a cognitive behavioural therapy (CBT) intervention implemented in a group setting either with or without the assistance of a social robot. The CBT protocol was based on Rational Emotive Behaviour Therapy (REBT) principles. Pre- and post-intervention assessments were conducted using the Test of Emotional Comprehension (TEC) and the Emotional Lexicon Test (ELT). Substantial improvements in contextualized emotion recognition, comprehension and emotional perspective-taking through the use of human-assisted social robots were attained., Author(s): Flavia Marino [sup.1] , Paola Chilà [sup.1] , Stefania Trusso Sfrazzetto [sup.1] , Cristina Carrozza [sup.1] , Ilaria Crimi [sup.1] , Chiara Failla [sup.1] , Mario Busà [sup.1] , [...]

A whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) method is used to identify a previously undescribed syndrome characterized by recurrent duplications of Xp11.22-p11.23 chromosomes associated with mental retardation, speech delay, and EEG anomalies in males and females. Research reveals that most of the rearrangements are mediated by recombinations between adjacent complex segmental duplications.

Orange-fleshed sweet potato (OFSP) is an important source of [beta]-carotene ([beta]C). Provitamin A bioefficacy from plant foods is influenced by dietary fat and fiber. We fed 3% OFSP powder diets with varying amounts of fat and soluble fiber to vitamin A (VA)-depleted Mongolian gerbils (n = 85) for 3 wk (8 groups, n = 10/group; control, n = 9) following a baseline kill (n = 6). OFSP diets differing in fat (3, 6, and 12%) contained 0.24% soluble fiber. Two additional 3% OFSP diets contained 6% fat and 3 or 9% white-fleshed sweet potato (WFSP) powder with soluble fiber contents of 0.42 and 0.80%, respectively. Control, VA-, and [beta]C-supplemented groups were included. Simulated digestion experiments compared the bioaccessibility of [beta]C from boiled vs. oil stir-fried OFSP. All OFSP diets maintained VA status and 12% fat and WFSP-added diets improved VA status above baseline (P < 0.05). Bioefficacy, as bioconversion factors, in gerbils fed 12% fat (3.5 [+ or -] 1.4 [micro]g [beta]C:1 [micro]g VA) was improved over the 3% fat and [beta]C groups (6.5 [+ or -] 3.7 and 6.7 [+ or -] 3.7 [micro]g [beta]C:1 [micro]g VA, respectively) (P < 0.05) but did not differ from WFSP-added groups or the 6% fat group with no WFSP. Stir-frying doubled the efficiency of [beta]C incorporation into micelles during small intestinal digestion in support of the stimulatory effect of dietary fat on bioefficacy in vivo. Soluble fiber intake derived from WFSP did not influence bioefficacy. Replacing WFSP with OFSP will affect VA status if adopted by target groups.

The ratio of cis and all-trans lycopene (LYC) in human and animal tissues exceeds that in foods. The basis for this difference remains unknown, although differences in their stability, transport, and metabolism have been suggested. Here, we systematically compared the digestive stability, efficiency of micellarization, and uptake and intracellular stability of cis and all-trans isomers of LYC and carotenes using the coupled in vitro digestion and Caco-2 human intestinal cell model. Aril and oil from the carotenoid-rich gac fruit (Momordica cochinchinensis Spreng) were cooked with rice to provide a natural source of LYC and carotenes. The ratio of cis:trans isomers of LYC and/3-carotene was similar before and after simulated gastric and small intestinal digestion with recovery of total carotenoids in the digesta exceeding 70%. Micellarization of cis isomers of LYC during digestion of meals with both gac aril and oil was significantly greater than that of the all-trans isomer but less than for the carotenes. Uptake of cis isomers of LYC by Caco-2 cells was similar to that of carotenes and significantly greater than all-trans LYC. Micellarized carotenoids were relatively stable in micelles incubated in the cell culture environment and after accumulation in Caco-2 cells. These data suggest that the greater bioaccessibility of cis compared with all-trans isomers of LYC contributes to the enrichment of the cis isomers in tissues and that gac fruit is an excellent source of bioaccessible LYC and provitamin A carotenoids.

Cassava, a staple food in sub-Saharan Africa, does not provide adequate amounts of pro-vitamin A (VA) carotenoids and has been targeted for biofortification (i.e. selectively breeding cultivars of increased nutrient density with agroeconomically acceptable characteristics). However, the accessibility of pro-VA carotenoids for absorption in different cultivars of cassava remains unknown. Here, we used the coupled in vitro digestion/Caco-2 cell uptake model to screen the relative accessibility of [beta]-carotene ([beta]C) in 10 cultivars of cassava with varying concentrations of [beta]C. After cooking (boiled for 30 min), the [beta]C concentration in tubers from different cultivars ranged from less than detectable to 6.9 [micro]g [beta]C/g cassava. Samples were subjected to simulated oral, gastric, and small intestinal digestion to determine stability and micellarization of [beta]C. All-trans [beta]C, 9-cis [beta]C, and 13-cis [beta]C were the most abundant carotenoids in cooked cassava and recoveries after digestion exceeded 70%. Efficiency of micellarization of total [beta]C was 30 [+ or -] 2% for various cultivars with no significant difference in isomers and linearly proportional to concentration in cooked cassava (r = 0.87; P < 0.001). Accumulation of all-trans [beta]C by Caco-2 cells incubated with the diluted micelle fraction for 4 h was proportional ([R.sup.2] = 0.99; P < 0.001) to the quantity present in micelles. These results suggest that all-trans [beta]C content appears to provide the key selection marker for breeding cassava to improve VA status and that the more complicated screening procedure using in vitro digestion coupled to cell uptake does not provide additional information on potential bioavailability.

The morphological and rheological properties of a commercial propylene-ethylene copolymer (PEC) and a series of blends with different concentrations of poly (ethylene-co-propylene) are investigated. The blends are prepared mixing PEC with fractions obtained from it by solvent extraction. The phase structure of samples exposed to different thermal and mechanical histories was analyzed using scanning electron microscopy. The linear viscoelastic properties of the molten polymers were measured using different test sequences that include dynamic frequency and time sweeps. The phase structure of most blends changes dramatically with time when the polymers are kept in the molten state due to the coalescence of the domains. For example, the initial morphology of PEC which presents domains of ~1 µm diameter changes to regions of more than 10 µm of average diameter after 90 min at 178°C at rest. Coincidentally, the dynamic moduli of the blends change during annealing reaching values that depend on the mechanical history. For example, the elastic modulus of PEC increases ~32% during a dynamic time sweep of 45 min using a frequency of 0.1 [s.sup.-1], while it decreases ~18% when a frequency of 0.1 [s.sup.-1] is applied. Moreover, the modulus measured at 0.1 [s.sup.-1] of samples annealed at rest during 45 min is ~58% larger than that of the fresh material. POLYM. ENG. SCI., 47:912-921, 2007. © 2007 Society of Plastics Engineers, INTRODUCTION Since the production of polypropylene (PP) began in 1957, great research effort has been directed towards the improving of the low temperature impact behavior of this material. The most [...]

Carnosine is an endogenously synthesized dipeptide composed of [beta]-alanine and L-histidine. It acts as a free radical scavenger and possesses antioxidant properties. Carnosine reduces proinflammatory and profibrotic cytokines such as transforming growth factor-[beta] (TGF-[beta]), IL-l, and TNF-[alpha] in different experimental settings. In the present study, we investigated the efficacy of carnosine on the animal model of bleomycin-induced lung injury. Mice were subjected to intratracheal administration of bleomycin and were assigned to receive carnosine daily by an oral bolus of 150 mg/kg. One week after fibrosis induction, bronchoalveolar lavage (BAL) cell counts and TGF-[beta] levels, lung histology, and immunohistochemical analyses for myeloperoxidase, TGF-[beta], inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase were performed. Finally, apoptosis was quantified by terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay. After bleomycin administration, carnosine-treated mice exhibited a reduced degree of lung damage and inflammation compared with wild-type mice, as shown by the reduction of 1) body weight, 2) mortality rate, 3) lung infiltration by neutrophils (myeloperoxidase activity and BAL total and differential cell counts), 4) lung edema, 5) histological evidence of lung injury and collagen deposition, 6) lung myeloperoxidase, TGF-[beta], inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase immunostaining, 7) BAL TGF-[beta] levels, and 8) apoptosis. Our results indicate that orally administered carnosine is able to prevent bleomycin-induced lung injury likely through its direct antioxidant properties. Carnosine is already available for human use. It might prove useful as an add-on therapy for the treatment of fibrotic disorders of the lung where oxidative stress plays a role, such as for idiopathic pulmonary fibrosis, a disease that still represents a major challenge to medical treatment. lung fibrosis; oxidative stress; chelating agent doi:10.1152/ajplung.00283.2006

I INTRODUCTION The importance of international cooperation as a basis upon which the global refugee system functions was first recognised in the Preamble to the 1951 Convention Relating to the [...], Despite a proclaimed commitment of the &apos;developed West&apos; to international cooperation in the formation of durable solutions for refugees, a pattern of defensive policy designed to outsource obligations under the 1951 Refugee Convention has emerged. In this context, on 26 September 2014, Australia and Cambodia signed a &apos;responsibility sharing&apos; agreement for the relocation to Cambodia of recognised refugees who originally sought protection in Australia and were removed to Nauru for processing. Whilst the Cambodia Agreement is of particular relevance in the Australasian region, this paper will analyse its nature and effect against the backdrop of the global trend of burden shifting and the implications of such an agreement for international law. This paper will examine whether the Cambodia Agreement complies with the 1951 Refugee Convention through an analysis of the potential issues with fulfilment of the rights found therein. This requires the establishment of a continuum of jurisdiction pursuant to which it is concluded that transferees under the Cambodia Agreement remain under the effective jurisdiction of Australia. This paper concludes that while a developing country may have the capacity to provide the requisite standard of protection to refugees under the 1951 Refugee Convention, in practice Cambodia fails to do so.

Zeaxanthin (Zea) and lutein are the only dietary carotenoids that accumulate in the macular region of the retina and lens. It was proposed that these carotenoids protect these tissues against photooxidative damage. Few plant foods are enriched in Zea, and information about the bioavailability of Zea from these foods and its accumulation in ocular tissues is limited. The amounts of free Zea and its mono- and diesters were measured for several plant foods that have relatively high concentrations of this xanthophyll. Wolfberry had the greatest concentration of Zea with a diester that accounts for 95% of the total. Free, mono-, and diesters of Zea were present in orange and red peppers, whereas only Zea monoesters were detected in squash. Zea esters were partially hydrolyzed by carboxyl ester lipase (CEL) during simulated digestion. The efficiency of micellarization was dependent on speciation with combined means of free Zea, Zea monoesters, Zea diesters from the digested foods of 81 [+ or -] 8, 44 [+ or -] 5, and 11 [+ or -] 4%, respectively. When exposed to micelles generated during digestion of the test foods, Zea uptake by Caco-2 cells was proportional to the medium content (11-14%). Free Zea was the most abundant form in Caco-2 cells, although Zea monoesters also were detected ( KEY WORDS: * bioavailability * carboxyl ester lipase * Caco-2 cells * wolfberry * zeaxanthin

ABSTRACT--In this paper we provide a review of wavelet analysis in the context of applications to vibrations problems. First, we give an introduction to the important concepts and mathematical properties [...]

Epidemiological studies suggest that consumption of vegetables rich in the xanthophylls lutein (LUT) and zeaxanthin (ZEA) reduces the risk for developing age-related cataract, a leading cause of vision loss. Although LUT and ZEA are the only dietary carotenoids present in the lens, direct evidence for their photoprotective effect in this organ is not available. The present study examined the effects of xanthophylls and [alpha]-tocopherol ([alpha]-TC) on lipid peroxidation and the mitogen-activated stress signaling pathways in human lens epithelial (HLE) cells following ultraviolet B light (UVB) irradiation. When presented with LUT, ZEA, astaxanthin (AST), and [alpha]-TC as methyl-[beta]-cyclodextrin complexes, HLE cells accumulated the lipophiles in a concentration- and time-dependent manner with uptake of LUT exceeding that of ZEA and AST. Pretreatment of cultures with either 2 [micro]mol/L xanthophyll of 10 [micro]mol/L [alpha]-TC for 4 h before exposure to 300 J/[m.sup.2] UVB radiation decreased lipid peroxidation by 47-57% compared with UVB-treated control HLE cells. Pretreatment with the xanthophylls and [alpha]-TC also inhibited UVB-induced activation of c-JUN N[H.sub.2]-terminal kinase (JNK) and p38 by 50-60 and 25-32%, respectively. There was substantial inhibition of UVB-induced JNK and p38 activation for cells containing 2.3 nmol [alpha]-TC/mg protein was required to significantly decrease UVB-induced stress signaling. These data suggest that xanthophylls are more potent than [alpha]-TC for protecting human lens epithelial cells against UVB insult. KEY WORDS: * lutein * zeaxanthin * MAPK stress signaling * lipid peroxidation * human lens epithelial cells

It is rapidly becoming possible to measure hundreds or thousands of metabolites in small samples of biological fluids or tissues. This makes it possible to assess the metabolic component of nutritional phenotypes and will allow individualized dietary recommendations. ASNS has to take action to ensure that appropriate technologies are developed and that metabolic databases are constructed with the right inputs and organization. The relations between diet and metabolomic profiles and between those profiles and health and disease must be established. ASNS also should consider the social implications of these advances and plan for their appropriate utilization.

Lutein and zeaxanthin are selectively accumulated in the lens and macular region of the retina. It was suggested that these xanthophylls protect ocular tissues from free-radical damage that can cause cataracts and age-related macular degeneration. Insights regarding the absorption of dietary xanthophylls for delivery to ocular tissues are limited. Our primary objective was to examine factors affecting the transfer of lutein from foods to absorptive intestinal epithelial cells during digestion. Lutein and other carotenoids present in spinach puree and lutein from a commercial supplement were relatively stable during in vitro digestion. Micellarization of lutein and zeaxanthin during the small intestinal phase of digestion exceeded that of [beta]-carotene and was greater for xanthophylls in oil-based supplements than in spinach. Apical uptake of lutein from micelles by Caco-2 human intestinal cells was linear for at least 8 h, and accumulation from synthetic micelles exceeded that from micelles generated during simulated digestion. Stimulation of chylomicron synthesis resulted in the secretion of 7.6 [+ or -] 0.1% of cellular lutein into the triglyceride-rich fraction in the basolateral chamber. These data support the use of simulated digestion and the Caco-2 cell model as effective tools for identifying factors affecting absorption of dietary carotenoids. KEY WORDS: * lutein * bioavailability * in vitro digestion * micelles * Caco-2 human intestinal cells

A wavelets-based method is developed to estimate the evolutionary power spectral density (EPSD) of nonstationary stochastic processes. The method relies on the property that the continuous wavelet transform of a nonstationary process can be treated as a stochastic process with EPSD given in terms of the EPSD of the process in a closed form. This yields an equation in the frequency domain relating the instantaneous mean-square value of the wavelet transform to the EPSD of the process. A number of these equations are considered, each related to a certain scale of the wavelet transform, in conjunction with representing the target EPSD as a sum of time-independent shape functions modulated by time-dependent coefficients; the squared moduli of the Fourier transforms of the wavelets associated with the selected scales are taken as shape functions. This leads to a linear system of equations which is solved to determine the unknown time-dependent coefficients; the same system matrix applies for all time instances. Numerical examples demonstrate the accuracy and computational efficiency of the proposed method. DOI: 10.1061/(ASCE)0733-9399(2004)130:8(952) CE Database subject headings: Stationary processes; Earthquakes; Spectra; Spectral density function; Stochastic processes.

This study investigated the psychometric properties of the Impact of Event Scale--Revised (IES-R) in two samples of male Vietnam veterans: a treatment-seeking sample with a confirmed posttraumatic stress disorder (PTSD) diagnosis (N = 120) and a community sample with varying levels of traumatic stress symptomatology (N = 154). The scale showed high internal consistency (alpha = 0.96). Confirmatory factor analysis did not provide support for a three-factor solution corresponding to the three subscales of intrusion, avoidance, and hyperarousal. Exploratory factor analysis suggested that either a single, or a two-factor solution (intrusion/hyperarousal and avoidance), provided the best account of the data. However, correlations among the subscales were higher in the community sample than in the treatment sample, suggesting that the IES-R may be sensitive to a more general construct of traumatic stress in those with lower symptom levels. The correlation between the IES-R and the PTSD Checklist was high (0.84) and a cutoff of 1.5 (equivalent to a total score of 33) was found to provide the best diagnostic accuracy. Keywords: PTSD; IES-R; PCL; Veterans

This paper deals with the estimation of spectral properties of randomly excited multi-degree-of-freedom (MDOF) nonlinear vibrating systems. Each component of the vector of the stationary system response is expanded into a trigonometric Fourier series over an adequately long interval T. The unknown Fourier coefficients of individual samples of the response process are treated by harmonic balance, which leads to a set of nonlinear equations that are solved by Newton's method. For polynomial nonlinearities of cubic order, exact solutions are developed to compute the Fourier coefficients of the nonlinear terms, including those involved in the Jacobian matrix associated with the implementation of Newton's method. The proposed technique is also applicable for arbitrary nonlinearities via a cubicization procedure over the interval T. Upon determining the Fourier coefficients, estimates of the response power spectral density matrix are constructed by averaging their squared moduli over the samples ensemble. Examples of application prove the reliability of the technique by comparison with digital simulation data. [DOI: 10.1115/1.1599916]

The molecular structure of several high-density polyethylenes of different molecular weights and vinyl contents was modified without altering their thermoplastic character using an organic peroxide. Chain linking was the main chemical event that occurred during the modification process. Samples of these polymers were crystallized from the melt, generating materials with different morphologies. Two crystallization procedures were followed: slow cooling and quenching. The density and crystallinity of the polymers were found to be slightly dependent on the molecular structures generated by the modification process. Tensile tests were performed at room temperature to evaluate the mechanical behavior of the polymers. The mechanical response of some of the slowly cooled samples changed from brittle to ductile when increasing concentrations of peroxide were added to the formulation. All the quenched samples displayed ductile behavior. The elastic modulus and yield stress were found to increase linearly with the crystallinity of the polymers independently of the molecular structure generated by the modification process. The molecular weight of the modified polymers appears to be the main structural property that influences the draw ratio after break and the ultimate tensile stress of the samples. The draw ratio diminishes, while the ultimate tensile stress increases with the molecular weight of the polymers, irrespective of the evolution of other molecular parameters., INTRODUCTION The treatment of polyethylene (PE) with organic peroxides at temperatures above its melting point is a well-known process used to change the thermo-mechanical properties of these polymers (1, 2). [...]

Several proposed biotechnological applications of green fluorescent protein (GFP) are likely to result in its introduction into the food supply of domestic animals and humans. We fed pure GFP and diets containing transgenic canola expressing GFP to young male rats for 26 d to evaluate the potential toxicity and allergenicity of GFP. Animals (n = 8 per group) were fed either AIN-93G (control), control diet plus 1.0 mg of purified GFP daily, modified control diet with 200 g/kg canola (Brassica rapa cv Westar), or control diet with 200 g/kg transgenic canola containing one of two levels of GFP. Ingestion of GFP did not affect growth, food intake, relative weight of intestine or other organs, or activities of hepatic enzymes in serum. Comparison of the amino acid sequence of GFP to known food allergens revealed that the greatest number of consecutive amino acid matches between GFP and any food allergen was four, suggesting the absence of common allergen epitopes. Moreover, GFP was rapidly degraded during simulated gastric digestion. These data indicate that GFP is a low allergenicity risk and provide preliminary indications that GFP is not likely to represent a health risk. J. Nutr. 133: 1909-1912, 2003. KEY WORDS: * green fluorescent protein * food safety * toxicity * allergenicity * genetically modified food

Although it is widely recognized that essential trace elements are required for the differentiation, activation and performance of numerous functions of immune cells, the specific roles of these inorganic micronutrients in these processes remain largely undefined. New insights about the participation of zinc, iron and copper in the selection, maturation and early activation events of the immune cells have been gained by judicious use of available tools in analytical cell biology, molecular genetics and array technology. Also, randomly controlled clinical and community trials demonstrate that zinc supplementation can enhance immunocompetence and decrease the incidence and severity of some infections in individuals with diagnosed or suspected mild zinc deficiency. These exciting results provide an impetus to evaluate the potential benefits of supplementation programs for individuals and groups with suboptimal trace element status as a cost-effective means of reducing the risk of infectious diseases. KEY WORDS: * immunity * zinc * copper * iron * cytokines * cell activation * nuclear factor-[kappa]B

Random vibrations of nonlinear systems subjected to Gaussian input are investigated by a technique based on statistical quadratization, and cubicization. In this context, and depending on the nature of the given nonlinearity, statistics of the stationary response are obtained via an equivalent system with a polynomial nonlinearity of either quadratic or cubic order, which can be solved by the Volterra series method. The Volterra series response is expanded in a trigonometric Fourier series over an adequately long interval T, and exact expressions are derived for the Fourier coefficients of the second- and third-order response in terms of the Fourier coefficients of the first-order, Gaussian response. By using these expressions, statistics of the response are determined using the statistics of the Fourier coefficients of the first-order response, which can be readily computed since these coefficients are independent zero-mean Gaussian variables. In this manner, a significant reduction of the computational cost is achieved, as compared to alternative formulations of quadratization and cubicization methods where rather prohibitive multifold integrals in the frequency domain must be determined. Illustrative examples demonstrate the reliability of the proposed technique by comparison with data from pertinent Monte Carlo simulations. CE Database keywords: Oscillators; Nonlinear systems; Random vibration; Gaussian process.

A new approach to measuring the sizes of small fluorescent objects by use of spatially modulated illumination (SMI) far-field light microscopy is presented. This method is based on SMI measurements combined with a new SMI virtual microscopy (VIM) data analysis calibration algorithm. Here, experimental SMI measurements of fluorescent objects with known diameter (size) were made. From the SMI data obtained, the size was determined in an independent way by use of the SMI VIM algorithm. The results showed that with SMI microscopy in combination with SMI VIM calibration, subwavelength object size measurements as small as 40 nm are experimentally feasible with high accuracy. OCIS codes: 100.0100, 110.0180, 180.0180, 180.2520, 180.3170, 180.6900.

A new approach for determining the sizes of individual, small fluorescent objects with diameters considerably below the optical resolution limit is described in which spatially modulated illumination (SMI) microscopy and 360-647-nm excitation wavelengths are used. The results of SMI virtual microscopy computer simulations indicate that, in this wavelength range, reliable measurements of sizes as small as ~20 nm are feasible if the low numbers of fluorescence photons that are usually detected from such small objects are taken into account. This method is based on the well-known fact that the modulation of the diffraction image in a SMI microscope is disturbed by the size of the object. Using appropriately calculated calibration functions, one can use this disturbance of the modulation to determine the size of the original object. OCIS codes: 100.0100, 180.0180.

This study presents a new statistical cubicization approach for predicting the stochastic response of offshore platforms subjected to a Morison-type nonlinear drag loading. Statistics of the original system are obtained from an equivalent nonlinear system, which is constructed by replacing the Morison drag force by a cubic polynomial function of the relative fluid-structure velocity, up to cubic order. A Volterra series expansion with a finite Fourier series representation is used to approximate the response of the equivalent system. Exact solutions are developed to express the Fourier coefficients of the second and third-order response as functions of the Fourier coefficients of the first-order relative fluid-structure velocity. Response statistics are then computed by ensemble averaging over a suitable number of realizations of the first-order Gaussian response. Response statistics up to the sixth order, computed for a variety of sea conditions, show accuracy and efficiency of the proposed method as compared to digital simulation.

For an improved understanding of the structural basis of cellular mechanisms, it is highly desirable to develop methods for a detailed topological analysis of biological nanostructures and their dynamics in the interior of three-dimensionally conserved cells. We present a method of far-field laser fluorescence microscopy to measure relative axial positions of pointlike fluorescent targets and the distance between each target in the range of a few nanometers. The physical principle behind this approach can be extended to the determination of three-dimensional (3D) positions and 3D distances between any number of objects that can be discriminated owing to their spectral signature, thus allowing topological measurements so far regarded to be beyond the capabilities of light microscopy. OCIS codes: 100.6890, 140.3570, 170.2520, 180.3170.

A polyclonal antiserum specific for the Wilson's disease ATPase was employed to investigate the hepatic expression of this protein. Immunoblot examination of lysates from human and rat liver indicated a single 165-kDa protein, which by immunofluorescence was found only in hepatocytes and localized mostly in the trans-Golgi network and exclusively in this compartment under low hepatic copper concentrations. Findings revealed a unique posttranslational mechanism of copper homeostasis in vivo which is in agreement with the suggested role of the Wilson's disease protein in heloceruloplasmin biosynthesis and biliary copper excretion.

Byline: Bernardo Ventimiglia (1), F. Patti (2), Ester Reggio (2), Gaetano Failla (2), Carmelo Morana (1), Maria Lopes (1), Francesco Savoca (1), Carmelo Consoli (1), Arturo Reggio (2) Keywords: Key words Urology; Neurology; Micturition disorders; Protocol Abstract: Our aim was to evaluate the utility and effectiveness of a study protocol for neurourological involvement in neurological disorders. We studied a sample of 786 patients with neurological disorders followed by the Neurological Department of Catania University and applied to them a four-step diagnostic protocol. Fifty-six per cent of the sample showed urological functional abnormalities only 78 patients (9.9%) presented with an organic urological disease. Among the vesicosphincteric dysfunctions, bladder hyperreflexia was the most common pattern with remarkable differences between diseases. The present study demonstrated the utility of a standardized urological protocol in the screening and detection of neurourological involvement in neurological diseases. Our protocol showed good specificity and reasonable low costs. Author Affiliation: (1) Institue of Urology, University of Catania, Italy, IT (2) Servizio di Neuroriabilitazione e Sclerosi Multipla, Istituto di Scienze Neurologiche, Policlinico Universitario, Viale Andrea Doria, 6, I-95125 Catania, Italy Tel.: +39-338-6270548 +39-95-330533 Fax: +39-95-330943 e-mail: patti.francesco@gte.it, FR Article note: Received: 5 June 1997 Received in revised form: 21 October 1997 Accepted: 6 November 1997

The reduction of the trace mineral copper in T cells suggests a compromise in resistance to infectious disease. Animal and cellular experiments show an adequate amount of copper is responsible for the development of and function of cells that make up the immune system. The exact role of copper needs further study.

Numerous epidemiological studies support a strong inverse relationship between consumption of carotenoid-rich fruits and vegetables and the incidence of some degenerative diseases. One proposed mechanism of protection by carotenoids centers on their putative antioxidant activity, although direct evidence in support of this contention is limited at the cellular level. The antioxidant potential of [Beta]-carotene (BC) and lutein (LUT), carotenoids with or without pro-vitamin A activity, respectively, was evaluated using the human liver cell line HepG2. Pilot studies showed that a 90-min exposure of confluent cultures to 500 [[micro]mol]/L tert-butylhydroperoxide (TBHP) at 37 [degrees] C significantly (P < 0.05) increased lipid peroxidation and cellular leakage of lactate dehydrogenase (LDH), and decreased the uptake of 3H-[Alpha]-aminoisobutyric acid and 3H-2-deoxyglucose. Protein synthesis, mitochondrial activity and glucose oxidation were not affected by TBHP treatment, suggesting that the plasma membrane was the primary site of TBHP-induced damage. Overnight incubation of cultures with [greater than or equal to]1 [[micro]mol]/L dl-[Alpha]-tocopherol protected cells against oxidant-induced changes. In parallel studies, overnight incubation of HepG2 in medium containing micelles with either BC or LUT (final concentrations of 1.1 and 10.9 [[micro]mol]/L, respectively), the cell content of the carotenoids increased from < 0.04 to 0.32 and 3.39 nmol/mg protein, respectively. Carotenoid-loaded cells were partially or completely protected against oxidant-induced changes in lipid peroxidation, LDH release and amino acid and deoxyglucose transport. These data demonstrate that BC and LUT or their metabolites protect HepG2 cells against oxidant-induced damage and that the protective effect is independent of provitamin A activity. J. Nutr. 126: 2098-2106, 1996. INDEXING KEY WORDS: * carotenoids * antioxidant * amino acid transport * glucose transport * HepG2 human cell line

Double yields, as well as other complex yielding behavior, that are observed during the tensile deformation of the polyethylenes have been studied in a systematic manner. The conditions under which such yielding is observed were established by studying a set of linear polyethylenes and well-characterized ethylene copolymers of narrow molecular weight and composition distributions. A wide range in crystallinity levels were developed and the rate of deformation and the deformation temperature were varied. These experimental results make clear why such complex yielding processes are not always observed. A qualitative explanation, based on the postulate of a partial melting-recrystallization process during deformation, is given that encompasses all of the experimental data., INTRODUCTION Several years ago in the course of a detailed study of the tensile properties of the polyethylenes we reported that, with just a few exceptions, structurally irregularly chains, i.e. [...]