Quantitative peripheral computed tomodensitometric study of cortical and trabecular bone mass in relation with menopause

Lymphocyte subpopulations (B cells, CD4, CD8), interleukin-20 receptors (IL-2), monocytes/macrophages (Leu M5), and HLA-DR antigen expression were studied immunohistochemically on frozen sections from 38 bladder cancer specimens. T cells predominated over B cells in all tumours. CD4-positive lymphocytes predominated over CD8 in the stroma (CD4/CD8: 1.35/l), while in epithelial tumour cells CD8 was the prominent subpopulation (CD8/CD4: 1.75/l). Aberrant HLA-DR expression was found in 21.05 per cent of bladder tumours. A strong correlation between CD4 and CD8 population densities and macrophages with the other subpopulations was noticed. In HLA-DR-positive tumours, there was no correlation of the percentage of positive cells with CD4- and CD8-positive lymphocyte populations. Various parameters including IL-2 receptors, B cells, CD8- and CD4-positive cells, and macrophages did not differ significantly between the groups of tumours expressing and not expressing HLA-DR antigen. There were no statistically significant differences in the population densities of B cells, CD8- or CD4-positive cells, IL-2 receptor, monocytes/macrophages, and HLA-DR antigen expression among various clinicopathological parameters, including growth pattern, histological grade and clinical stage or patient's age and sex. These findings suggest that in transitional cell carcinoma of the urinary bladder, HLA-DR antigen expression is independent of lymphocyte subpopulations. It is therefore possible that HLA-DR expression by tumour cells reflect the existence of separate HLA-DR-positive or HLA-DR-negative tumour clones.     

Toward a Novel Drug To Target the EGF–EGFR Interaction: Design of Metabolically Stable Bicyclic Peptides

In cancer, proliferation of malignant cells is driven by overactivation of growth‐signalling mechanisms, such as the epidermal growth factor receptor (EGFR) pathway. Despite its therapeutic relevance, the EGF–EGFR interaction has remained elusive to inhibition by synthetic molecules, mostly as a result of its large size and lack of binding pockets and cavities. Designed peptides, featuring cyclic motifs and other structural constraints, have the potential to modulate such challenging protein–protein interactions (PPIs). Herein, we present the structure‐based design of a series of bicyclic constrained peptides that mimic an interface domain of EGFR and inhibit the EGF–EGFR interaction by targeting the smaller partner (i.e., EGF). This design process was guided by the integrated use of in silico methods and biophysical techniques, such as NMR spectroscopy and surface acoustic wave. The best analogues were able to reduce selectively the viability of EGFR+ human cancer cells. In addition to their efficacy, these bicyclic peptides are endowed with exceptional stability and metabolic resistance—two features that make them suitable candidates for in vivo applications.     

Envelopes and waves: safe multivehicle collision avoidance for horizontal non-deterministic turns

International Journal on Software Tools for Technology Transfer - We present an approach to analyze the safety of asynchronous, independent, non-deterministic, turn-to-bearing horizontal maneuvers...     

Evaluation of Text Entry Methods for Interactive Digital Television Applications with Devices Alternative to Conventional Remote Controls

The popularity of Interactive Digital Television (IDTV) applications has grown in recent years, playing a significant role in today’s society. This new type of television allows users to access interactive applications in order to look for information, for communication or educational purposes, or just for fun. Most of these applications require text entry and many users expect a user experience similar to that of computers. Although the most common device to interact with television is the conventional remote control, other devices available on the market may be used in this context. Thus, in this article we aim to evaluate and compare different text input methods for IDTV applications using devices alternative to conventional remote controls. We have carried out an empirical study with 52 participants. We analyze entry speeds, error rates, and subjective impressions for six different entry methods, taking into account the particular characteristics of the users. As devices we have used a full-sized keyboard, a palm-sized keyboard, a gyroscopic remote point-select, and a modified touchpad. The fastest method is the standard keyboard, but in an IDTV context many users report discomfort and problems under low lighting conditions. Also, error rates are considerably higher with both keyboards when modifier keys need to be used. The results obtained with the gyroscopic remote and the touchpad are similar. Nevertheless, while users complain about fatigue problems with the former, their feedback about the latter is very positive. We have also observed that age is a major factor affecting the performance of the users. We expect our results to contribute to the design of new text entry methods for IDTV.     

A comparative study of many-objective evolutionary algorithms for the discovery of software architectures

During the design of complex systems, software architects have to deal with a tangle of abstract artefacts, measures and ideas to discover the most fitting underlying architecture. A common way to structure such complex systems is in terms of their interacting software components, whose composition and connections need to be properly adjusted. Along with the expected functionality, non-functional requirements are key at this stage to guide the many design alternatives to be evaluated by software architects. The appearance of Search Based Software Engineering (SBSE) brings an approach that supports the software engineer along the design process. Evolutionary algorithms can be applied to deal with the abstract and highly combinatorial optimisation problem of architecture discovery from a multiple objective perspective. The definition and resolution of many-objective optimisation problems is currently becoming an emerging challenge in SBSE, where the application of sophisticated techniques within the evolutionary computation field needs to be considered. In this paper, diverse non-functional requirements are selected to guide the evolutionary search, leading to the definition of several optimisation problems with up to 9 metrics concerning the architectural maintainability. An empirical study of the behaviour of 8 multi- and many-objective evolutionary algorithms is presented, where the quality and type of the returned solutions are analysed and discussed from the perspective of both the evolutionary performance and those aspects of interest to the expert. Results show how some many-objective evolutionary algorithms provide useful mechanisms to effectively explore design alternatives on highly dimensional objective spaces.     

A formally verified hybrid system for safe advisories in the next-generation airborne collision avoidance system

The Next-Generation Airborne Collision Avoidance System (ACAS X) is intended to be installed on all large aircraft to give advice to pilots and prevent mid-air collisions with other aircraft. It is currently being developed by the Federal Aviation Administration (FAA). In this paper, we determine the geometric configurations under which the advice given by ACAS X is safe under a precise set of assumptions and formally verify these configurations using hybrid systems theorem proving techniques. We consider subsequent advisories and show how to adapt our formal verification to take them into account. We examine the current version of the real ACAS X system and discuss some cases where our safety theorem conflicts with the actual advisory given by that version, demonstrating how formal hybrid systems proving approaches are helping to ensure the safety of ACAS X. Our approach is general and could also be used to identify unsafe advice issued by other collision avoidance systems or confirm their safety.     

Unusual Lipid A from a Cold‐Adapted Bacterium: Detailed Structural Characterization

Colwellia psychrerythraea 34H is a Gram‐negative cold‐adapted microorganism that adopts many strategies to cope with the limitations associated with the low temperatures of its habitat. In this study, we report the complete characterization of the lipid A moiety from the lipopolysaccharide of Colwellia. Lipid A and its partially deacylated derivative were completely characterized by high‐resolution mass spectrometry, NMR spectroscopy, and chemical analysis. An unusual structure with a 3‐hydroxy unsaturated tetradecenoic acid as a component of the primary acylation pattern was identified. In addition, the presence of a partially acylated phosphoglycerol moiety on the secondary acylation site at the 3‐position of the reducing 2‐amino‐2‐deoxyglucopyranose unit caused tremendous natural heterogeneity in the structure of lipid A. Biological‐activity assays indicated that C. psychrerythraea 34H lipid A did not show an agonistic or antagonistic effect upon testing in human macrophages.     

On-line 2-satisfiability

We deal with the followingon-line 2-satisfiability problemP(m, n): starting fromC(0)=true, consider a sequence ofm Boolean formulasC(k) (inn variables and in conjunctive normal form), each of them being the intersection of the previous one with a single clause which is the union of two literals. Solve the sequence of 2-satisfiability problemsC(k)=true,k=1,...,m. It is well known that a 2-satisfiability problem involvingm clauses can be solved inO(m) time. Thus, by a naive approach one can solveP(m, n) in overallO(m ²) time. We present an algorithm with overallO(nm) time complexity, which for every formula not only checks its satisfiability, but also actually computes a solution (if any), and moreover, detects all forced and all identical variables. Our algorithm makes use of an efficient on-line transitive closure procedure by Italiano. We discuss two applications to the design of integrated electronic circuits and to edge classification in automated perception.To the memory of Bob Jeroslow