Chromo-dynamic multi-component lattice Boltzmann equation scheme for axial symmetry

We validate the chromo-dynamic multi-component lattice Boltzmann equation (MCLBE) simulation for immiscible fluids with a density contrast against analytical results for complex flow geometries, with particular emphasis on the fundamentals of the method, i.e. compliance with inter-facial boundary conditions of continuum hydrodynamics. To achieve the necessary regimes for the chosen validations, we develop, from a three-dimensional, axially-symmetric flow formulation, a novel, two-dimensional, pseudo Cartesian, MCLBE scheme. This requires the inclusion in lattice Boltzmann methodology of a continuously distributed source and a velocity-dependent force density (here, the metric force terms of the cylindrical Navier–Stokes equations). Specifically, we apply our model to the problem of flow past a spherical liquid drop in Re = 0, Ca regime and, also, flow past a lightly deformed drop. The resulting simulation data, once corrected for the simulation’s inter-facial micro-current (using a method we also advance herein, based on freezing the phase field) show good agreement with theory over a small range of density contrasts. In particular, our data extend verified compliance with the kinematic condition from flat (Burgin et al 2019 Phys. Rev. E 100 043310) to the case of curved fluid–fluid interfaces. More generally, our results indicate a route to eliminate the influence of the inter-facial micro-current

Exploiting the plasticity of primary and secondary response mechanisms in artificial immune systems

One of the key properties of the human immune system is to detect the presence of pathogens, and as such there are numberous immune algorithm which perform anomaly detection and pattern recognition. An additional facet of the human immune system is that an appropriate effector response is generated upon the detection of a pathogen - a process termed the primary response. Additionally the human immune system has the ability to remember the appropriate response to a particular pathogen - the secondary response. The complex orchestration of both the primary and secondary responses are highly dynamic - described in immunological terms as plastic. In this paper we present an overview of the the exact mechanisms of the generation of a T-helper cell primary response and the mechanisms by which it instructs secondary responses and discuss how this can be computationally useful in artificial immune system development

Total loss of MHC class I is an independent indicator of good prognosis in breast cancer

Tumours can be recognised by CTL and NK cells. CTL recognition depends on expression of MHC Class I loaded with peptides from tumour antigens. In contrast, loss of MHC Class I results in NK activation. In our study a large set of samples from patients with primary operable invasive breast cancer was evaluated for the expression of MHC Class I heavy and light by immunohistochemical staining of 439 breast carcinomas in a tissue microarray. Forty-seven percent (206 of 439) of breast carcinomas were considered negative for HLA Class I heavy chain (HC10), whereas lack of anti-β2m-antibody staining was observed in 39% (167 of 424) of tumours, with only 3% of the β2m-negative tumours expressing detectable HLA Class I heavy chain. Correlation with patient outcome showed direct relationship between patient survival and HLA-negative phenotype (log rank = 0.004). A positive relationship was found between the intensity of expression of MHC Class I light and heavy chains expression and histological grade of invasive tumour (p < 0.001) and Nottingham Prognostic Index (p < 0.001). To investigate whether HLA Class I heavy and light chains expression had independent prognostic significance, Cox multivariate regression analysis, including the parameters of tumour size, lymph node stage, grade and intensity of HC10 and anti-β2m staining, was carried out. In our analysis, lymph node stage (p < 0.001), tumour grade (p = 0.005) and intensity of MHC Class I light and heavy chains expression were shown to be independent prognostic factors predictive of overall survival (p-values HC10 = 0.047 and β2m = 0.018)

Evidence that the p53 negative / Bcl-2 positive phenotype is an independent indicator of good prognosis in colorectal cancer: A tissue microarray study of 460 patients

BACKGROUND: Advances in our understanding of the molecular biology of colorectal cancer have fuelled the search for novel molecular prognostic markers to complement existing staging systems. Markers assessed in combination may perform better than those considered individually. Using high-throughput tissue microarray technology, we describe the prognostic value of combined p53 / Bcl-2 status in colorectal cancer. PATIENTS AND METHODS: Tumour samples from 462 patients who underwent elective surgery to resect a primary colorectal cancer between 1994 and 2000 (mean follow-up of 75 months) were assembled in tissue microarray format. Clinico-pathological data including tumour grade, stage, vascular invasion status along with disease specific survival data has been collected prospectively. Immunohistochemical analysis of p53 and Bcl-2 expression was performed using antibodies DO-7 (p53) and 124 (Bcl-2), and results correlated with known clinico-pathological variables and outcomes. RESULTS: Abnormal nuclear p53 accumulation and Bcl-2 overexpression were detected in 221/445 (49.6%) and199/437 (45.5%) tumours respectively, with a significant inverse correlation between the two markers (p = 0.023). On univariate analysis no correlations were found between either marker and standard clinico-pathological variables, however nuclear p53 expression was associated with a significantly reduced survival (p = 0.024). Combined analysis of the two markers indicated that 112/432 (24.2%) cases displayed a p53(-)/Bcl-2(+) phenotype, this occurring more frequently in earlier stage tumours. Kaplan-Meier analysis revealed a significant survival advantage in these p53(-)/Bcl-2(+) tumours compared with the remaining cases (p = 0.0032). On multivariate analysis using the Cox proportional hazards model, neither p53 expression nor Bcl-2 expression alone were of independent prognostic significance, however the combined p53(-)/Bcl-2(+) phenotype was significantly associated with a good prognosis in this series (HR 0.659, 95%CI 0.452–0.959, p = 0.029). CONCLUSION: Patient stratification by combined p53 / Bcl-2 phenotype provides stage-independent prognostic information in colorectal cancer. Specifically, that up to a quarter of patients display a good prognosis p53(-)/Bcl-2(+) phenotype. This may indicate a more clinically indolent phenotype and a subset of patients for whom less aggressive adjuvant treatment appropriate

Chromodynamic multirelaxation-time lattice Boltzmann scheme for fluids with density difference

We develop, after Dellar ( P. J. Dellar, Phys. Rev. E. 65, 036309 (2002), J. Comput. Phys. 190, pp351 (2003)), a multiple-relaxation time (MRT), chromodynamic, multi-component lattice Boltzmann equation (MCLBE) scheme for simulation of isothermal, immiscible fluid flow with a density contrast. It is based on Lishchuk’s method (J. U. Brackbill, D. B. Kothe and C. Zemach, J. Comp. Phys. 100, 335-354 (1992), S. V. Lishchuk, C. M. Care and I. Halliday, Phys. Rev. E. 67(3), 036701(2), (2003)) and the segregation of d’Ortona et al. (U. D’Ortona, D. Salin, M. Cieplak, R. B. Rybka and J. R. Banavar Phys. Rev. E. 51, 3718, (1995)). We focus on fundamental model verifiability but do relate some of our data to that from previous approaches, due to Ba et al. (Y. Ba, H. Liu, Q. Li, Q. Kang and J. Sun, Phys. Rev. E 94, 023310 (2016)) and earlier Liu et al. (H. Liu, A. J. Valocchi and Q. Kang, Phys. Rev. E 85, 046309 (2012)), who pioneered large density difference chromodynamic MCLBE and showed the practical benefits of a MRT collision model. Specifically, we test the extent to which chromodynamic MCLBE MRT schemes comply with the kinematic condition of mutual impenetrability and the continuous traction condition by developing analytical benchmarking flows. We conclude that our data, taken with those of Ba et al., verify the utility of MRT chromodynamic MCLBE

Three-dimensional single framework multi-component lattice Boltzmann equation method for vesicle hydrodynamics

We develop a three dimensional immersed boundary chromodynamic multi-component lattice Boltzmann method capable of simulating vesicles, such as erythrocytes. The presented method is encapsulated in a single framework, where the application of the immersed boundary force in the automatically adaptive interfacial region results in correct vesicle behaviour. We also set-down a methodology for computing the principal curvatures of a surface in a three-dimensional, physical space which is defined solely in terms of its surface normal vectors. The benefits of such a model are its transparent methodology, stability at high levels of deformation, automatic-adaptive interface and potential for the simulation of many erythrocytes. We demonstrate the utility of the model by examining the steady state properties, as well as dynamical behaviour within shear flow. The stability of the method is highlighted through its handling of high deformations, as well as interaction with another vesicle

Molecular expression patterns in the synovium and their association with advanced symptomatic knee osteoarthritis

Objective: Osteoarthritis (OA) is a major source of knee pain. Mechanisms of OA knee pain are incompletely understood but include synovial pathology. We aimed to identify molecular expression patterns in the synovium associated with symptomatic knee OA.Design: Snap frozen synovia were from people undergoing total knee replacement (TKR) for advanced OA, or from post-mortem (PM) cases who had not sought help for knee pain. Associations with OA symptoms were determined using discovery and validation samples, each comprising TKR and post mortem (PM) cases matched for chondropathy (Symptomatic or Asymptomatic Chondropathy). Associations with OA were determined by comparing age matched TKR and PM control cases. Real-time quantitative PCR for 96 genes involved in inflammation and nerve sensitisation used TaqMan® Array Cards in discovery and validation samples, and protein expression for replicated genes was quantified using Luminex bead assay.Results: Eight genes were differentially expressed between asymptomatic and symptomatic chondropathy cases and replicated between discovery and validation samples (P3-fold change). Of these, matrix metalloprotease (MMP)-1 was also increased whereas interleukin-1 receptor 1 (IL1R1) and vascular endothelial growth factor (VEGF) were decreased at the protein level in the synovium of symptomatic compared to asymptomatic chondropathy cases. MMP1 protein expression was also increased in OA compared to PM controls.Conclusion: Associations of symptomatic OA may suggest roles of MMP1 expression and IL1R1 and VEGF pathways in OA pain. Better understanding of which inflammation-associated molecules mediate OA pain should inform refinement of existing therapies and development of new treatments

A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation

Gut microbes have a substantial influence on systemic immune function and allergic sensitisation. Manipulation of the gut microbiome through prebiotics may provide a potential strategy to influence the immunopathology of asthma. This study investigated the effects of prebiotic Bimuno-galactooligosaccharide (B-GOS) supplementation on hyperpnoea-induced bronchoconstriction (HIB), a surrogate for exercise-induced bronchoconstriction, and airway inflammation. A total of ten adults with asthma and HIB and eight controls without asthma were randomised to receive 5·5 g/d of either B-GOS or placebo for 3 weeks separated by a 2-week washout period. The peak fall in forced expiratory volume in 1 s (FEV1) following eucapnic voluntary hyperpnoea (EVH) defined HIB severity. Markers of airway inflammation were measured at baseline and after EVH. Pulmonary function remained unchanged in the control group. In the HIB group, the peak post-EVH fall in FEV1 at day 0 (−880 (SD 480) ml) was unchanged after placebo, but was attenuated by 40 % (−940 (SD 460) v. −570 (SD 310) ml, P= 0·004) after B-GOS. In the HIB group, B-GOS reduced baseline chemokine CC ligand 17 (399 (SD 140) v. 323 (SD 144) pg/ml, P =0·005) and TNF-α (2·68 (SD 0·98) v. 2·18 (SD 0·59) pg/ml, P= 0·040) and abolished the EVH-induced 29 % increase in TNF-α. Baseline C-reactive protein was reduced following B-GOS in HIB (2·46 (SD 1·14) v. 1·44 (SD 0·41) mg/l, P=0·015) and control (2·16 (SD 1·02) v. 1·47 (SD 0·33) mg/l, P=0·050) groups. Chemokine CC ligand 11 and fraction of exhaled nitric oxide remained unchanged. B-GOS supplementation attenuated airway hyper-responsiveness with concomitant reductions in markers of airway inflammation associated with HIB

Connexin 43 is an independent predictor of patient outcome in breast cancer patients

PurposeGap junctions are specialized membrane structures that form channels between adjacent cells allowing cell communication. Gap junctions and specifically Connexin 43 (Cx43) are down-regulated in cancer; however, there are contrasting reports on how this effects breast cancer patient survival. This paper is the first large-scale tissue microarray analysis of Cx43 expression in breast cancer patients with an associated clinical long-term follow-up.MethodsUsing a validated TMA of 1118 primary breast cancers, coupled to a comprehensive database of clinicopathological variables, the expression levels and subcellular localisation of Cx43 was assessed by immunohistochemistry. Its impact in terms of survival, distant metastasis-free survival, and clinicopathological variables was determined.ResultsPatients whose tumors expressed high levels of Cx43 had significantly better survival (p