A robust approach to model densification and crack formation in powder compaction processes

This paper deals with the question of how to efficiently integrate a constitutive model that describes the densification of powders and the potential formation of cracks in Powder Metallurgy (P/M) cold compaction processes. The analyzed model is a large strain, elastoplastic model of the Drucker–Prager/Cap type, refined to cover also the prediction of crack formation, and featuring non-conventional elements such as a density-dependent Von Mises yield surface; a parabolic plastic potential function for the Drucker–Prager envelope; and a softening law whose softening modulus is dependent on the level of densification. The employed integration procedure is a non-conventional hybrid or IMPLicit–EXplicit (IMPL-EX) scheme, whose essence is to solve explicitly for some variables and implicitly for others, with the peculiarity of the ‘explicit’ variables being but extrapolated values of the same quantities computed, at previous time steps, by means of a fully implicit scheme. The return-mapping equations stemming from this implicit scheme are solved using an unconditionally convergent, fractional step method-based iterative procedure. The performance of the IMPL-EX integration algorithm is critically assessed in two different situations: the densification of a cylindrical specimen, and the fracture process in a diametral compression test. Results obtained show conclusively that the proposed hybrid integration strategy offers an efficient solution to the trade-off between robustness and computational time requirement

A 3D Frictionless Contact Domain Method for Large Deformation Problems

This work describes a three-dimensional contact domain method for large deformation frictionless contact problems. Theoretical basis and numerical aspects of this specific contact method are given in [Oliver, Hartmann, Cante, Weyler and Hernández (2009)] and [Hartmann, Oliver, Weyler, Cante and Hernández (2009)] for two-dimensional, large deformation frictional contact problems. In this method, in contrast to many other contact formulations, the necessary contact constraints are formulated on a so-called contact domain, which can be interpreted as a fictive intermediate region connecting the potential contact surfaces of the deformable bodies. This contact domain has the same dimension as the contacting bodies. It will be endowed with a displacement field, interpolated from the displacements at the contact surfaces and will be subdivided into a non-overlapping set of contact patches, where the contact constraints will be applied. For the enforcement of these contact constraints a stabilized Lagrange multiplier method is used, which allows the condensation of the introduced Lagrange multipliers, leading to a purely displacement driven problem

A contact domain method for large deformation frictional contact problems. Part 1: Theoretical basis

In the first part of this work, the theoretical basis of a frictional contact domain method for two-dimensional large deformation problems is presented. Most of the existing contact formulations impose the contact constraints on the boundary of one of the contacting bodies, which necessitates the projection of certain quantities from one contacting surface onto the other. In this work, the contact constraints are formulated on a so-called contact domain, which has the same dimension as the contacting bodies. This contact domain can be interpreted as a fictive intermediate region connecting the potential contact surfaces of the deformable bodies. The introduced contact domain is subdivided into a non-overlapping set of patches and is endowed with a displacement field, interpolated from the displacements at the contact surfaces. This leads to a contact formulation that is based on dimensionless, strain-like measures for the normal and tangential gaps and that exactly passes the contact patch test. In addition, the contact constraints are enforced using a stabilized Lagrange multiplier formulation based on an interior penalty method (Nitsche method). This allows the condensation of the introduced Lagrange multipliers and leads to a purely displacement driven problem. An active set strategy, based on the concept of effective gaps as entities suitable for smooth extrapolation, is used for determining the active normal stick and slip patches of the contact domain

A contact domain method for large deformation frictional contact problems. Part 2: Numerical aspects

This second part of the work describes the numerical aspects of the developed contact domain method for large deformation frictional contact problems. The theoretical basis of this contact method is detailed in the first part of this work. Starting from this, the present contribution focuses on describing important algorithmic details that go along with the finite element implementation for two-dimensional problems. Important aspects are the construction of the contact domain mesh, via a constraint Delaunay triangulation, the linearization of the discretized contact contributions and some important technical aspects about the extrapolation procedure used for the predictive active set strategy. Finally a set of numerical examples is presented to demonstrate the performance of the developed contact strategy. Demanding static and dynamic contact problems in the context of large deformations, including frictional effects as well as self contact, show the wide applicability and the robustness of the proposed metho

Prognostic value of bcl-2 expression in invasive breast cancer.

Expression of the bcl-2 proto-oncogene was studied immunohistochemically in 251 invasive ductal breast carcinomas (median follow-up time 91 months, range 24-186 months) and the results were correlated with clinicopathological data and prognostic variables. Sixty-three (25%) tumours were scored bcl-2 negative and 188 (75%) tumours were bcl-2 positive. No relationship could be observed between bcl-2 status and tumour grade, pTNM staging or menopausal status. A strong positive relationship was demonstrated between bcl-2 immunoreactivity and oestrogen receptor status (P < 0.001) and progesterone receptor status (P < 0.001). No prognostic value was demonstrated for bcl-2 expression on disease-free survival and overall survival in axillary node-negative breast cancer patients. However, in axillary node-positive breast cancer patients multivariate analysis demonstrated absence of bcl-2 expression to be independently related to shortened disease-free survival (P = 0.003) and shortened overall survival (P < 0.001). Our results suggest a potential important role for bcl-2 expression as a modulator of response to adjuvant therapy in breast cancer

Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer.

Tumour stromal neovascularization was investigated in 114 invasive and 20 in situ carcinomas of the uterine cervix by staining representative sections with the specific endothelial marker anti CD31 (clone JC/70A, isotope IgG1). A digital image analyser was used to measure the immunoreactivity. The following parameters were determined in the 'hot spots': vessel counts, vessel perimeter and endothelial stained area (expressed per mm2). The results were correlated with clinical and histopathological data. There was no significant relationship between the histopathological findings (tumour histology, tumour differentiation, FIGO stage, presence of lymph node metastasis or lymphovascular space involvement) and the median vessel count. In a univariate analysis all angiogenesis parameters had prognostic value: a higher vascularity was associated with worse prognosis (P < 0.05). Multiple regression analysis showed that vascular permeation (P < 0.001) and the median vessel count (P = 0.005) were the most important prognostic indicators. In the future these criteria may be used for selection of patients for anti-angiogenesis therapy

Prognostic value of nonangiogenic and angiogenic growth patterns in non-small-cell lung cancer

An essential prerequisite of nonangiogenic growth appears to be the ability of the tumour to preserve the parenchymal structures of the host tissue. This morphological feature is visible on a routine tissue section. Based on this feature, we classified haematoxylin and eosin-stained tissue sections from 279 patients with non-small-cell lung cancer into three growth patterns: destructive (angiogenic; n=196), papillary (intermediate; n=38) and alveolar (nonangiogenic; n=45). A Cox multiple regression model was used to test the prognostic value of growth patterns together with other relevant clinicopathological factors. For overall survival, growth pattern (P=0.007), N-status (P=0.001), age (P=0.020) and type of operation (P=0.056) were independent prognostic factors. For disease-free survival, only growth pattern (P=0.007) and N-status (P&lt;0.001) had an independent prognostic value. Alveolar (hazard ratio=1.825, 95% confidence interval=1.117-2.980, P=0.016) and papillary (hazard ratio=1.977, 95% confidence interval=1.169-3.345, P=0.011) growth patterns were independent predictors of poor prognosis. The proposed classification has an independent prognostic value for overall survival as well as for disease-free survival, providing a possible explanation for survival differences of patients in the same disease stage

The Differential Roles of T Cells in Non-alcoholic Fatty Liver Disease and Obesity

Non-alcoholic fatty liver disease (NAFLD) constitutes a spectrum of disease states characterized by hepatic steatosis and is closely associated to obesity and the metabolic syndrome. In non-alcoholic steatohepatitis (NASH), additionally, inflammatory changes and hepatocellular damage are present, representing a more severe condition, for which the treatment is an unmet medical need. Pathophysiologically, the immune system is one of the main drivers of NAFLD progression and other obesity-related comorbidities, and both the innate and adaptive immune system are involved. T cells form the cellular component of the adaptive immune system and consist of multiple differentially active subsets, i.e., T helper (Th) cells, regulatory T (Treg) cells, and cytotoxic T (Tc) cells, as well as several innate T-cell subsets. This review focuses on the role of these T-cell subsets in the pathogenesis of NAFLD, as well as the association with obesity and type 2 diabetes mellitus, reviewing the available evidence from both animal and human studies. Briefly, Th1, Th2, Th17, and Th22 cells seem to have an attenuating effect on adiposity. Th2, Th22, and Treg cells seem to decrease insulin resistance, whereas Th1, Th17, and Tc cells have an aggravating effect. Concerning NAFLD, both Th22 and Treg cells appear to have an overall tempering effect, whereas Th17 and Tc cells seem to induce more liver damage and fibrosis progression. The evidence regarding the role of the innate T-cell subsets is more controversial and warrants further exploration

Rare association between cystic fibrosis, Chiari I malformation, and hydrocephalus in a baby: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Cystic fibrosis, an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator gene, is not generally associated with malformations of the central nervous system. We review eight previously published reports detailing an infrequent association between cystic fibrosis and Chiari I malformation.</p> <p>Case presentation</p> <p>To the best of our knowledge, our report describes only the ninth case of a baby presenting with a new diagnosis of cystic fibrosis and Chiari I malformation, in this case in a 10-month-old, full-term Caucasian baby boy from the United States of America. Neurosurgical consultation was obtained for associated developmental delay, macrocephaly, bulging anterior fontanel, and papilledema. An MRI scan demonstrated an extensive Chiari I malformation with effacement of the fourth ventricle, obliteration of the outlets of the fourth ventricle and triventricular hydrocephalus without aqueductal stenosis. Our patient was taken to the operating room for ventriculoperitoneal shunt placement.</p> <p>Conclusions</p> <p>It is possible that the cystic fibrosis transmembrane conductance regulator gene may play a previously unrecognized role in central nervous system development; alternatively, this central nervous system abnormality may have been acquired due to constant valsalva from recurrent coughing or wheezing or metabolic and electrolyte imbalances that occur characteristically in cystic fibrosis.</p

Seventh supplement to the Federated Malay States Government Gazette of Friday, the 7th of December, 1925 (Vol. XVII, No. 24).

No. 779