A scheme to aid construction of left-hand sides of axioms in algebraic specifications for object-oriented program testing

In order to ensure reliability and quality, software systems must be tested. Testing object-oriented software is harder than testing procedure-oriented software. It involves four levels, namely the algorithmic level, class level, cluster level, and system level. We proposed a methodology TACCLE for class-and cluster- level testing. It includes an important algorithm GFT for generating fundamental equivalent pairs as class-level test cases based on axioms in a given algebraic specification for a given class. This formal methodology has many benefits. However, system analysts often find it difficult to construct axioms for algebraic specifications. In this paper, we propose a scheme to aid the construction of the left-hand sides of axioms. The scheme alleviates the difficulties of the system analysts and also helps them check the completeness, consistency, and independence of the axiom system. © 2008 IEEE.published_or_final_versionUnion Grant of Guangdong Province and National Natural Science Foundation of China (#U0775001), Guangdong Province Science Foundation (#7010116), and by a grant of the Youth Science Foundation of Jinan University (#51208035)

Lean implementations of software testing tools using XML representations of source codes

By utilizing XML representations of source programs under test, a new approach is proposed to concisely implement some prototypes for TACCLE, a software testing methodology. The conversions between a source program and its XML representation can be easily realized using existing conversion tools. In this way, the conversion tools can automatically analyze and parse the source program, so that testing tool developers only need to concentrate on the manipulation of the XML document. If appropriate XML DOM APIs are chosen, the implementations of such testing tools will be pretty lean. A detailed case study for GMPS tool, a prototype for the TACCLE methodology, is presented to illustrate the new approach. © 2008 IEEE.published_or_final_versionThis research is supported by the Jinan University Youth Foundation under Grant #51208035, Union Grant of Guangdong Province and National Natural Science Foundation of China under Grant #U0775001, and the Guangdong Province Science Foundation under Grant #7010116

Transplanted Olfactory Ensheathing Cells Reduce Retinal Degeneration in Royal College of Surgeons Rats

PURPOSE OF THE STUDY: Retinitis pigmentosa (RP) is a group of genetic disorders and a slow loss of vision that is caused by a cascade of retinal degenerative events. We examined whether these retinal degenerative events were reduced after cultured mixtures of adult olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts (ONFs) were transplanted into the subretinal space of 1-month-old RCS rat, a classic model of RP. MATERIALS AND METHODS: The changes in retinal photoreceptors and Müller cells of RCS rats after cell transplantation were observed by the expression of recoverin and glial fibrillary acidic protein (GFAP), counting peanut agglutinin (PNA)-positive cone outer segments and calculating the relative apoptotic area. The retinal function was also evaluated by Flash electroretinography (ERG). To further investigate the mechanisms, by which OECs/ONFs play important roles in the transplanted retinas, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF) secretion of the cultured cells were analyzed by ELISA. The ability of OECs/ONFs to ingest porcine retinal outer segments and the amount of phagocytosis were compared with retinal pigment epithelium (RPE) cells. RESULTS: Our research showed that the transplantation of OECs/ONFs mixtures restored recoverin expression, protected retinal outer segments, increased PNA-positive cone outer segments, reduced caspase-positive apoptotic figures, downregulated GFAP, and maintained the b-wave of the ERG. Cultured OECs/ONFs expressed and secreted NGF, BDNF, and bFGF which made contributions to assist survival of the photoreceptors. An in vitro phagocytosis assay showed that OECs, but not ONFs, phagocytosed porcine retinal outer segments, and the phagocytic ability of OECs was even superior to that of RPE cells. CONCLUSIONS: These findings demonstrate that transplantation of OECs/ONFs cleaned up the accumulated debris in subretinal space, and provided an intrinsic continuous supply of neurotrophic factors. It suggested that transplantation of OECs/ONFs might be a possible future route for protection of the retina and reducing retinal degeneration in RP

Compromised BRCA1-PALB2 interaction is associated with breast cancer risk.

The major breast cancer suppressor proteins BRCA1 and BRCA2 play essential roles in homologous recombination (HR)-mediated DNA repair, which is thought to be critical for tumor suppression. The two BRCA proteins are linked by a third tumor suppressor, PALB2, in the HR pathway. While truncating mutations in these genes are generally pathogenic, interpretation of missense variants remains a challenge. To date, patient-derived missense variants that disrupt PALB2 binding have been identified in BRCA1 and BRCA2; however, there has not been sufficient evidence to prove their pathogenicity in humans, and no variants in PALB2 that disrupt either its BRCA1 or BRCA2 binding have been reported. Here we report on the identification of a novel PALB2 variant, c.104T>C (p.L35P), that segregates in a family with a strong history of breast cancer. Functional analyses showed that L35P abrogates the PALB2-BRCA1 interaction and completely disables its abilities to promote HR and confer resistance to platinum salts and PARP inhibitors. Whole-exome sequencing of a breast cancer from a c.104T>C carrier revealed a second, somatic, truncating mutation affecting PALB2, and the tumor displays hallmark genomic features of tumors with BRCA mutations and HR defects, cementing the pathogenicity of L35P. Parallel analyses of other germline variants in the PALB2 N-terminal BRCA1-binding domain identified multiple variants that affect HR function to varying degrees, suggesting their possible contribution to cancer development. Our findings establish L35P as the first pathogenic missense mutation in PALB2 and directly demonstrate the requirement of the PALB2-BRCA1 interaction for breast cancer suppression

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung

Structure of hadron resonances with a nearby zero of the amplitude

We discuss the relation between the analytic structure of the scattering amplitude and the origin of an eigenstate represented by a pole of the amplitude.If the eigenstate is not dynamically generated by the interaction in the channel of interest, the residue of the pole vanishes in the zero coupling limit. Based on the topological nature of the phase of the scattering amplitude, we show that the pole must encounter with the Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the dynamical component of the eigenstate is small if a CDD zero exists near the eigenstate pole. We show that the line shape of the resonance is distorted from the Breit-Wigner form as an observable consequence of the nearby CDD zero. Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio

Clinical Usefulness of Measuring Red Blood Cell Distribution Width in Patients with Hepatitis B

BACKGROUND: Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (e.g., anisocytosis) that is largely overlooked, is a newly recognized risk marker in patients with cardiovascular diseases, but its role in persistent viral infection has not been well-defined. The present study was designed to investigate the association between RDW values and different disease states in hepatitis B virus (HBV)-infected patients. In addition, we analyzed whether RDW is associated with mortality in the HBV-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and twenty-three patients, including 16 with acute hepatitis B (AHB), 61 with chronic hepatitis B (CHB), and 46 with chronic severe hepatitis B (CSHB), and 48 healthy controls were enrolled. In all subjects, a blood sample was collected at admission to examine liver function, renal function, international normalized ratio and routine hematological testing. All patients were followed up for at least 4 months. A total of 10 clinical chemistry, hematology, and biochemical variables were analyzed for possible association with outcomes by using Cox proportional hazards and multiple regression models. RDW values at admission in patients with CSHB (18.30±3.11%, P<0.001), CHB (16.37±2.43%, P<0.001) and AHB (14.38±1.72%, P<0.05) were significantly higher than those in healthy controls (13.03±1.33%). Increased RDW values were clinically associated with severe liver disease and increased 3-month mortality rate. Multivariate analysis demonstrated that RDW values and the model for end-stage liver disease score were independent predictors for mortality (both P<0.001). CONCLUSION: RDW values are significantly increased in patients with hepatitis B and associated with its severity. Moreover, RDW values are an independent predicting factor for the 3-month mortality rate in patients with hepatitis B

Inhibition of Melanoma Growth by Subcutaneous Administration of hTERTC27 Viral Cocktail in C57BL/6 Mice

hTERTC27 is a 27 kDa C-terminal polypeptide of human telomerase reverse transcriptase that has previously been shown to reduce tumorigenicity of HeLa cells and suppress growth of xenografted glioblastoma in nude mice. Although ectopic expression of hTERTC27 upregulated genes that are involved in apoptosis, cell cycle, and immune response, the mechanism for hTERTC27-induced tumor suppression has not been completely elucidated. Since hTERT was identified as a universal tumor-associated antigen, we hypothesize that hTERTC27 inhibits tumor growth in vivo through activation of anti-tumor immune response. Immunocompetent C57BL/6 mice were used for mouse B16 melanoma model. Mice bearing B16 melanoma were administered rAAV-/rAdv viral cocktail expressing hTERTC27, and tumor growth was monitored after viral cocktail treatment. Blood and splenocytes were used to determine the level of cytokines and the activity of immune cells, respectively. B16 tumor growth was significantly inhibited by subcutaneous administration of a single dose of 1.5×10(11) vg rAAV-hTERTC27 and 2.5×10(9) pfu rAdv-hTERTC27 viral cocktail (rAAV-/rAdv-hTERTC27). The population and cytotoxicity of NK cells in the mice were significantly augmented by rAAV-/rAdv-hTERTC27 treatment, and selective depletion of the NK cell population in mice by intraperitoneal injection of anti-GM1 antibody abrogated the growth suppression of melanoma induced by rAAV-/rAdv-hTERTC27 administration. Activation of NK cells by administration of rAAV-/rAdv-hTERTC27 is critical for growth suppression of melanoma in mouse model.published_or_final_versio

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese

published_or_final_versio

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente