Delay spread measurements for the digital cellular channel inToronto

The paper describes a set of measurements performed in the Toronto area, in order to assess the impact of multipath propagation on the performance of the TIA IS-54 digital standard. Five existing cells were systematically surveyed: two in downtown Toronto, two in the suburbs, and one in a suburban/rural area. A sweeping correlator apparatus with a 0.1 μs resolution and 910 MHz carrier frequency, and an omnidirectional antenna was used. In one of the cells, the measurements were repeated with a 60 degree beamwidth directional antenna. A fairly sophisticated thresholding technique was applied in order to reduce the impact of noise. Generally, the measurements with the omnidirectional antenna exhibit multipath propagation with considerably smaller excess delays than some reported, but are consistent with earlier results obtained in the U.S. and Europe. Sectorization was found to considerably reduce the multipath effects. Very large delay components appear to be due mostly to the combination of large transmitter-receiver distances and a large degree of shadowing, and could probably be avoided to a large extent by standard cellular engineering techniques. In view of these results, it seems that the long delay (high selectivity) problem has been somewhat overemphasized in the past, at least for areas like Toronto. Problems associated with short delays (flat fading), on the contrary, appear to have been underestimated in the case of dense urban environments     

Determining the Tensile Stress-Crack Opening Curve of Concrete by Inverse Analysis

The determination of the fundamental stress versus crack opening (σ-w) response of concrete under uniaxial tension is performed in this study through inverse analysis using data from notched beam tests. The procedure used for optimizing the parameters of the σ-w relation using the load versus crack mouth opening displacement response of the notched beam is described. Satisfactory comparisons have been obtained between the σ-w curves obtained through the inverse analysis and those directly measured in uniaxial tension tests. The use of weighting functions in the inverse analysis may be necessary when large crack widths are to be considered.     

Density of 1,1-dichloro-1-fluoroethane (HCFC 141b) as a function of temperature and pressure

The density of HCFC 141b has been measured at several temperatures between 260 and 320 K, Mid pressures up to 20 MPa, with a mechanical oscillator densimeter. The densimeter was calibrated with 2,2,4-trimethylpentane, whose density was obtained from a correlating cyuation with 0.3% uncertainty. The density data obtained for HCFC 14H) hits a reproducibility of 0.05% and an uncertainty of 0.3%. The data obtained were fitted to a Tait-type equation. which reproduced the experimental densities within 0.11 % and were compared with the data obtained in other works.Paper presented at the Twelfth Symposium on Thermophysical Properties, June 19–24, 1994, Boulder, Colorado, U.S.A.     

Nephrotic syndrome. What is new since the 1988 study?

Hormone-refractory prostate cancer (HRPC) patients often have nonmeasurable disease. In such patients, predictive biomarkers other than tumor response may be required to compare therapeutic effects. We examined the predictive value for survival of various clinical and laboratory parameters, including prostate-specific antigen (PSA), in HRPC patients treated with suramin. Data from 103 HRPC patients were analyzed using various survival analyses, the likelihood ratio approach, and logistic regression analyses. When pretreatment factors, percentage decrease in PSA at 4 weeks from start of treatment (deltaPSA), and updated survival data were fit by a multivariate Cox proportional hazards model, acid phosphatase, lactate dehydrogenase, and deltaPSA were significant, with risk ratios close to 1. There was a decrease in likelihood ratio with increasing APSA. A logistic regression model was developed to predict the probability of <1 year of survival from the start of treatment. Hemoglobin and deltaPSA were found to be significant variables. However, in view of the complexities involving the relationship between PSA expression and prostate cancer growth and possible selective effect of treatment on PSA, further prospective testing is necessary. Therefore, deltaPSA cannot necessarily be used as a biomarker for survival response in individual patients during the evaluation of the therapeutic response of HRPC to new antineoplastic drugs.     

Evaluating a graphical notation for modelling software development methodologies

This work aims at evaluating a graphical notation for modelling software (and other kinds of) development methodologies, thus demonstrating how useful the graphical aspects can be for sharing knowledge between the people responsible for documenting information and those responsible for understanding and putting it into practice. We acknowledge the importance of having a common set of symbols that can be used to create, use and disseminate information for a larger audience than is possible today with a variety of alternatives and lack of a common ground. Using a cognitive dimensions framework, we make a standard evaluation of the elements and diagrams of the notation proposed to support the ISO/IEC 24744 methodology metamodel standard, considering the trade-offs between different dimensions. We suggest improvements to this existing notation based on this analysis, in the context of improving communication between creators and users of methodologies.     

Dehydropeptide Supramolecular Hydrogels and Nanostructures as Potential Peptidomimetic Biomedical Materials

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the N-terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, β-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,β-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area.     

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.     

Fabry Disease and the Heart: A Comprehensive Review

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.     

Syndecan-1 Depletion Has a Differential Impact on Hyaluronic Acid Metabolism and Tumor Cell Behavior in Luminal and Triple-Negative Breast Cancer Cells

Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors.