The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors that is characterized by three immunoglobulin-like domains and is expressed as a 140-kD disulphide-linked dimer

Human natural killer (NK) cells express inhibitory receptors that are specific for different groups of HLA-C or HLA-B alleles. The majority of these receptors belong to the immunoglobulin (Ig) superfamily and are characterized by two or three extracellular Ig-like domains. Here we describe a novel inhibitory NK receptor that is specific for a group of HLA-A alleles. The HLA-A3-specific NK cell clone DP7 has been used for mice immunization. Two mAbs, termed Q66 and Q241, bound to the immunizing clone and stained only a subset of NK cell populations or clones. Among Q66 mAb-reactive clones, we further selected those that did not express any of the previously identified HLA-class I-specific NK receptors. These clones did not lyse HLA-A3+ (or -A11+) target cells, but lysis of these targets could be detected in the presence of Q66 or Q241 mAbs. On the other hand, target cells expressing other HLA-A alleles, including -A1, -A2, and -A24, were efficiently lysed. Moreover, none of the HLA-C or HLA-B alleles that were tested exerted a protective effect. Q66+, but not Q66- NK cell clones, expressed messenger RNA coding for a novel 3 Ig domain protein homologous to the HLA-C (p58) and HLA-B (p70) receptors. The corresponding cDNA (cl.1.1) was used to generate transient and stable transfectants in COS7 and NIH3T3 cell lines, respectively. Both types of transfectants were specifically stained by Q66 and Q241 mAbs. Since the cytoplasmic tail of Q66-reactive molecules was at least 11 amino acid longer than the other known p58/p70 molecules, we could generate an antiserum specific for the COOH-terminus of Q66-reactive molecules, termed PGP-3. PGP-3 immunoprecipitated, only from Q66+ NK cells, molecules displaying a molecular mass of 140 kD, under nonreducing conditions, which resolved, under reducing conditions, in a 70-kD band. Thus, differently from the other p58/p70 receptors, Q66-reactive molecules appear to be expressed as disulphide-linked dimers and were thus termed p140. The comparative analysis of the amino acid sequences of p58, p70, and p140 molecules revealed the existence of two cysteins proximal to the transmembrane region, only in the amino acid sequence of p140 molecules.     

Lightweight coarse-grained coordination: a scalable system-level approach

In this paper, our solution to the problem of modelling functionally complex communication systems at the application level, based on lightweight coordination, is extended to seamlessly capture system-level testing as well. This extension could be realized simply by self-application: the bulk of the work for integrating system-level testing into our development environment, the ABC, concerned domain modelling, which can be done using the ABC. Therefore, the extension of the ABC to cover system-level testing was merely an application development on the basis of the ABC, illustrated here in the domain of Computer Telephony Integration. Here the adoption of a coarse-grained approach to test design, which is central to the scalability of the overall testing environment, is the enabling aspect for system-level test automation. Together with our lightweight coordination approach this induces an understandable modelling paradigm of system-wide test cases that is adequate for the needs and requirements of industrial test engineers. In particular, it enables test engineers to graphically design complex test cases that, in addition, can even be automatically checked for their intended purposes via model checking.     

Lipofilling in Breast Oncological Surgery: A Safe Opportunity or Risk for Cancer Recurrence?

Lipofilling (LF) is a largely employed technique in reconstructive and esthetic breast surgery. Over the years, it has demonstrated to be extremely useful for treatment of soft tissue defects after demolitive or conservative breast cancer surgery and different procedures have been developed to improve the survival of transplanted fat graft. The regenerative potential of LF is attributed to the multipotent stem cells found in large quantity in adipose tissue. However, a growing body of pre-clinical evidence shows that adipocytes and adipose-derived stromal cells may have pro-tumorigenic potential. Despite no clear indication from clinical studies has demonstrated an increased risk of cancer recurrence upon LF, these observations challenge the oncologic safety of the procedure. This review aims to provide an updated overview of both the clinical and the pre-clinical indications to the suitability and safety of LF in breast oncological surgery. Cellular and molecular players in the crosstalk between adipose tissue and cancer are described, and heterogeneous contradictory results are discussed, highlighting that important issues still remain to be solved to get a clear understanding of LF safety in breast cancer patients.     

Program verification and testing technologies

Program verification and testing techniques are crucial in fruitfully analyzing and validating complex software systems. This is an active research area and has produced various promising techniques in the last decade. However, many challenges lie ahead. We review the research area and summarize six papers selected from the Sixth International Symposium on Theoretical Aspects of Software Engineering (TASE 2012).     

Tool-supported enhancement of diagnosis in model-driven verification

We show on a case study from an autonomous aerospace context how to apply a game-based model-checking approach as a powerful technique for the verification, diagnosis, and adaptation of system behaviors based on temporal properties. This work is part of our contribution within the SHADOWS project, where we provide a number of enabling technologies for model-driven self-healing. We propose here to use GEAR, a game-based model checker, as a user-friendly tool that can offer automatic proofs of critical properties of such systems. Although it is a model checker for the full modal μ-calculus, it also supports derived, more user-oriented logics. With GEAR, designers and engineers can interactively investigate automatically generated winning strategies for the games, by this way exploring the connection between the property, the system, and the proof. This work has been partially supported by the European Union Specific Targeted Research Project SHADOWS (IST-2006-35157), exploring a Self-Healing Approach to Designing cOmplex softWare Systems. The project’s web page is at . This article is an extended version of Renner et al. [18] presented at ISoLA 2007, Poitiers, December 2007.     

Thymosin β4 is differentially expressed in the cerebrospinal fluid of Creutzfeldt‐Jakob disease patients: a MALDI‐TOF MS protein profiling study

MALDI‐TOF protein profiling analysis permits the detection of peptides and small proteins in complex protein mixtures with great accuracy. We applied this analysis to cerebrospinal fluid (CSF) from 15 patients affected by Creutzfeldt‐Jakob disease (CJD). We compared the levels of the normalized ion signals of 11 sporadic and 4 genetic CJD forms with those from ten healthy control subjects and eight non‐CJD relapsing‐remitting multiple sclerosis patients. In so doing, we detected 61 differentially expressed ion signals in CJD samples compared to controls. Among the 61 signals, 3 signals had significantly increased levels with high statistical significance (p <0.0001) and were located at 3238.3 m/z, 4963.7 m/z, and 8565.3 m/z. We characterized the 5.0 and 8.6 kDa proteins as thymosin β4 N‐acetylated and free ubiquitin, respectively, while the 3.2‐kDa peptide remained uncharacterized. Although elevated ubiquitin levels have previously been described in CJD, we have demonstrated for the first time the involvement of thymosin β4 in a neurodegenerative disease. To support the validity of thymosin β4 levels obtained by MALDI‐TOF analysis, an independent enzyme immunoassay analysis was performed. Moreover, a validation cohort consisting of CSF from three CJD patients, five healthy subjects, and six non‐CJD relapsing‐remitting multiple sclerosis patients was analyzed in a similar way, yielding superimposable results. We propose that thymosin β4 is a potential new candidate marker for the ante mortem diagnosis of CJD disease.     

Flexible Nanowire Cluster as a Wearable Colorimetric Humidity Sensor

Wearable plasmonic devices combine the advantages of high flexibility, ultrathinness, light weight, and excellent integration with the optical benefits mediated by plasmon‐enhanced electric fields. However, two obstacles severely hinder further developments and applications of a wearable plasmonic device. One is the lack of efficient approach to obtaining devices with robust antimotion‐interference property, i.e., the devices can work independently on the morphology changes of their working structures caused by arbitrary wearing conditions. The other issue is to seek a facile and high‐throughput fabrication method to satisfy the financial requirement of industrialization. In order to overcome these two challenges, a functional flexible film of nanowire cluster is developed, which can be easily fabricated by taking the advantages of both conventional electrochemical and sputtering methods. Such flexible plasmonic films can be made into wearable devices that work independently on shape changes induced by various wearing conditions (such as bending, twisting and stretching). Furthermore, due to plasmonic advantages of color controlling and high sensitivity to environment changes, the flexible film of nanowire cluster can be used to fabricate wearable items (such as bracelet, clothes, bag, or even commercial markers), with the ability of wireless visualization for humidity sensing.