Data Refinement of Remote Procedures

Recently the action systems formalism for parallel and distributed systems has been extended with the procedure mechanism. This gives us a very general framework for describing different communication paradigms for action systems, e.g. remote procedure calls. Action systems come with a design methodology based on the refinement calculus. Data refinement is a powerful technique for refining action systems. In this paper we will develop a theory and proof rules for the refinement of action systems that communicate via remote procedures based on the data refinement approach. The proof rules we develop are compositional so that modular refinement of action systems is supported. As an example we will especially study the atomicity refinement of actions. This is an important refinement strategy, as it potentially increases the degree of parallelism in an action system. Received February 1999 / Accepted in revised form July 2000     

Ab initio determination of heavy oxide perovskite related structures from precession electron diffraction data

Two complex perovskite-related structures were solved by ab initio from precession electron diffraction intensities. Structure models were firstly derived from HREM images and than have been confirmed independently using two and three-dimensional sets of precession intensities. Patterson techniques prove to be effective for ab initio structure resolution, specially in case of projections with no overlapping atoms. Quality of precession intensity data may be suitable enough to resolve unknown heavy oxide structures.     

Behavioral adaptation of information systems through goal models

Customizing software to perfectly fit individual needs is becoming increasingly important in information systems engineering. Users want to be able to customize software behavior through reference to terms familiar to their diverse needs and experience. We present a requirements-driven approach to behavioral customization of software systems. Goal models are constructed to represent alternative behaviors that users can exhibit to achieve their goals. Customization information is then added to restrict the space of possibilities to those that fit specific users, contexts, or situations. Meanwhile, elements of the goal models are mapped to units of source code. This way, customization preferences posed at the requirements level are directly translated into system customizations. Our approach, which we apply to an on-line shopping cart system and an automated teller machine simulator, does not assume adoption of a particular development methodology, platform, or variability implementation technique and keeps the reasoning computation overhead from interfering with the execution of the configured application.     

EDEN: An Intelligent Software Environment for Diagnosis of Discrete-Event Systems

A software environment, called EDEN, that prototypes a recent approach to model-based diagnosis of discrete-event systems, is presented. The environment integrates a specification language, called SMILE, a model base, and a diagnostic engine. SMILE enables the user to create libraries of models and systems, which are permanently stored in the model base, wherein both final and intermediate results of the diagnostic sessions are hosted as well. Given the observation of a physical system gathered during its reaction to an external event, the diagnostic engine performs the a posteriori reconstruction of all the possible evolutions of the system over time and, then, draws candidate diagnoses out of them. The diagnostic method is described using a simplified example within the domain of power transmission networks. Strong points of the method include compositional modeling, support for model update, ability to focus on any sub-system, amenability to parallel execution, management of multiple faults, and broad notions of system and observation.     

Josef Bro?ek: Friendship and History.

Presents reflections on the life and achievements of Josef Maria Bro?ek. The author notes that, in his way, Bro?ek turned psychology historiography into an international domain involving, in this construction, researchers from countries not only of Anglo Saxon languages but also those of Slavic and Latin languages, including Brazil. Quoting from Braque, he affirmed that "knowledge of the past enables the revelation of the present." However, he believed that "reality is not revealed if it is not sparkled by a poetic beam." The poetry of life illuminated Bro?ek and his actions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mass spectrometry for detection of 4-hydroxy-trans-2-nonenal (HNE) adducts with peptides and proteins

Despite the great technical advancement of mass spectrometry, this technique has contributed in a limited way to the discovery and quantitation of specific/precocious markers linked to free radical-mediated diseases. Unsaturated aldehydes generated by free radical-induced lipid peroxidation of polyunsaturated fatty acids, and in particular 4-hydroxy-trans-2 nonenal (HNE), are involved in the onset and progression of many pathologies such as cardiovascular (atherosclerosis, long-term complications of diabetes) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and cerebral ischemia). Most of the biological effects of HNE are attributed to the capacity of HNE to react with the nucleophilic sites of proteins and peptides (other than nucleic acids), to form covalently modified biomolecules that can disrupt important cellular functions and induce mutations. By considering the emerging role of HNE in several human diseases, an unequivocal analytical approach as mass spectrometry to detect/elucidate the structure of protein-HNE adducts in biological matrices is strictly needed not only to understand the reaction mechanism of HNE, but also to gain a deeper insight into the pathological role of HNE. This with the aim to provide intermediate diagnostic biomarkers for human diseases. This review sheds focus on the "state-of-the-art" of mass spectrometric applications in the field of HNE-protein adducts characterization, starting from the fundamental early studies and discussing the different MS-based approaches that can provide detailed information on the mechanistic aspects of HNE-protein interaction. In the last decade, the increases in the accessible mass ranges of modern instruments and advances in ionization methods have made possible a fundamental improvement in the analysis of protein-HNE adducts by mass spectrometry, and in particular by matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) tandem mass spectrometry. The recent developments and uses of combined analytical approaches to detect and characterize the type/site of interaction have been highlighted, and several other aspects, including sample preparation methodologies, structure elucidation, and data analysis have also been considered.     

Secure computation of hidden Markov models and secure floating-point arithmetic in the malicious model

Hidden Markov model (HMM) is a popular statistical tool with a large number of applications in pattern recognition. In some of these applications, such as speaker recognition, the computation involves personal data that can identify individuals and must be protected. We thus treat the problem of designing privacy-preserving techniques for HMM and companion Gaussian mixture model computation suitable for use in speaker recognition and other applications. We provide secure solutions for both two-party and multi-party computation models and both semi-honest and malicious settings. In the two-party setting, the server does not have access in the clear to either the user-based HMM or user input (i.e., current observations) and thus the computation is based on threshold homomorphic encryption, while the multi-party setting uses threshold linear secret sharing as the underlying data protection mechanism. All solutions use floating-point arithmetic, which allows us to achieve high accuracy and provable security guarantees, while maintaining reasonable performance. A substantial part of this work is dedicated to building secure protocols for floating-point operations in the two-party setting, which are of independent interest.     

Impact of Freeze-Drying on Cord Blood (CB), Serum (S), and Platelet-Rich Plasma (CB-PRP) Preparations on Growth Factor Content and In Vitro Cell Wound Healing

Blood-based preparations are used in clinical practice for the treatment of several eye disorders. The aim of this study is to analyze the effect of freeze-drying blood-based preparations on the levels of growth factors and wound healing behaviors in an in vitro model. Platelet-rich plasma (PRP) and serum (S) preparations from the same Cord Blood (CB) sample, prepared in both fresh frozen (FF) and freeze-dried (FD) forms (and then reconstituted), were analyzed for EGF and BDNF content (ELISA Quantikine kit). The human MIO-M1 glial cell line (Moorfield/Institute of Ophthalmology, London, UK) was incubated with FF and FD products and evaluated for cell migration with scratch-induced wounding (IncuCyte S3 Essen BioScience), proliferation with cyclin A2 and D1 gene expression, and activation with vimentin and GFAP gene expression. The FF and FD forms showed similar concentrations of EGF and BDNF in both the S and PRP preparations. The wound healing assay showed no significant difference between the FF and FD forms for both S and PRP. Additionally, cell migration, proliferation, and activation did not appear to change in the FD forms compared to the FF ones. Our study showed that reconstituted FD products maintained the growth factor concentrations and biological properties of FF products and could be used as a functional treatment option.     

CTLA4-Linked Autoimmunity in the Pathogenesis of Endometriosis and Related Infertility: A Systematic Review

Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid in patients with endometriosis-related infertility. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through a search of the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database and Web of Science, and Clinical Trials research register. We included observational or prospective human and animal studies with any features related to endometriosis and/or infertility studies involving CTLA4-related pathogenesis published in English. The results of studies in which the size and characteristics of the observed groups were not stated were excluded. From the initial pool of 73 publications identified and screened, we finally included 5 articles to summarize the most recent knowledge about CTLA4-linked autoimmunity in the pathogenesis of endometriosis and related infertility. Evidence from clinical studies shows that CTLA4-based autoimmunity is involved in the maintenance of chronic inflammation in the peritoneal environment, with pre-clinical evidence of anti-CTLA antibodies as a potential novel target therapy for endometriosis. However, CTLA4 gene analyses do not support findings of CTLA4-linked autoimmunity as a primary determinant of the pathogenesis of endometriosis. These findings underlie the role of complex interactions within the family of immune checkpoint molecules involved. Further studies are needed to investigate the clinical relevance of anti-CTLA target therapy, taking into account the potential adverse events and repercussions of novel immunologic therapy modalities. However, with the general scarcity of studies investigating this topic, the clinical importance of CTLA4 autoimmunity still remains unclear.     

Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients

DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile. This signature included ten Hedgehog (HH) pathways’ genes able to stratify multiple myeloma (MM) patients according to their self-renewal status. Results show that the designed assay is able to validate gene expression data, both in a retrospective as well as in a prospective cohort. In addition, the plasma cells’ differentiation status determined by ddPCR was further confirmed by other techniques, such as flow cytometry, allowing the identification of patients with immature plasma cells’ phenotype (i.e., expressing CD19+/CD81+ markers) upregulating HH genes, as compared to others, whose plasma cells lose the expression of these markers and were more differentiated. To our knowledge, this is the first technical report of gene expression data validation by ddPCR instead of classical qPCR. This approach permitted the identification of a Maturation Index through the integration of molecular and phenotypic data, able to possibly define upfront the differentiation status of MM patients that would be clinically relevant in the future.