Another algorithm for reducing bandwidth and profile of a sparse matrix

The paper describes a new bandwidth reduction method for sparse matrices which promises to be both fast and effective in comparison with known methods. The algorithm operates on the undirected graph corresponding to the incidence matrix induced by the original sparse matrix, and separates into three distinct phases: (1) determination of a spanning tree of maximum length, (2) modification of the spanning tree into a free level structure of small width, (3) level-by-level numbering of the level structure. The final numbering produced corresponds to a renumbering of the rows and columns of a sparse matrix so as to concentrate non-zero elements of the matrix in a band about the main diagonal

The age of the Galactic thin disk from Th/Eu nucleocosmochronology II. Chronological analysis

The purpose of this work is to resume investigation of Galactic thin disk dating using nucleocosmochronology with Th/Eu stellar abundance ratios, a theme absent from the literature since 1990. [Th/Eu] abundance ratios for a sample of 20 disk dwarfs/subgiants of F5 to G8 spectral type with -0.8 <= [Fe/H] <= +0.3, determined in the first paper of this series, were adopted for this analysis. We developed a Galactic chemical evolution model that includes the effect of refuses, which are composed of stellar remnants (white dwarfs, neutron stars and black holes) and low-mass stellar formation residues (terrestrial planets, comets, etc.), contributing to a better fit to observational constraints. Two Galactic disk ages were estimated, by comparing literature data on Th/Eu production and solar abundance ratios to the model ((8.7 +5.8-4.1) Gyr), and by comparing [Th/Eu] vs. [Fe/H] curves from the model to our stellar abundance ratio data ((8.2 +/- 1.9) Gyr), yielding the final, average value (8.3 +/- 1.8) Gyr. This is the first Galactic disk age determined via Th/Eu nucleocosmochronology, and corroborates the most recent white dwarf ages determined via cooling sequence calculations, which indicate a low age (<~ 10 Gyr) for the disk.Comment: 9 pages, 7 Postscript figures, accepted for publication in Astronomy & Astrophysics, final versio

Long-term cerebral thromboembolic complications of transapical endocardial resynchronization therapy

Purpose: Cardiac resynchronization therapy (CRT) is an established therapeutic option in selected heart failure patients (pts). However, the transvenous left ventricular (LV) lead implantation remains ineffectual in a considerable number of pts. Transapical LV (TALV) lead implantation is an alternative minimally invasive, surgical, endocardial implantation technique. The aim of the present prospective study is to determine the long-term outcome, including the cerebral thromboembolic complications, of pts

Fibroblast growth factor receptor 5 (FGFR5) is a co-receptor for FGFR1 that is up-regulated in beta-cells by cytokine-induced inflammation

Fibroblast growth factor receptor-1 (FGFR1) activity at the plasma membrane is tightly controlled by the availability of co-receptors and competing receptor isoforms. We have previously shown that FGFR1 activity in pancreatic beta-cells modulates a wide range of processes, including lipid metabolism, insulin processing, and cell survival. More recently, we have revealed that co-expression of FGFR5, a receptor isoform that lacks a tyrosine-kinase domain, influences FGFR1 responses. We therefore hypothesized that FGFR5 is a co-receptor to FGFR1 that modulates responses to ligands by forming a receptor heterocomplex with FGFR1. We first show here increased FGFR5 expression in the pancreatic islets of nonobese diabetic (NOD) mice and also in mouse and human islets treated with proinflammatory cytokines. Using siRNA knockdown, we further report that FGFR5 and FGFR1 expression improves beta-cell survival. Co-immunoprecipitation and quantitative live-cell imaging to measure the molecular interaction between FGFR5 and FGFR1 revealed that FGFR5 forms a mixture of ligand-independent homodimers (25%) and homotrimers (75%) at the plasma membrane. Interestingly, co-expressed FGFR5 and FGFR1 formed heterocomplexes with a 2:1 ratio and subsequently responded to FGF2 by forming FGFR5/FGFR1 signaling complexes with a 4:2 ratio. Taken together, our findings identify FGFR5 as a co-receptor that is up-regulated by inflammation and promotes FGFR1-induced survival, insights that reveal a potential target for intervention during beta-cell pathogenesis

Long-term cerebral thromboembolic complications of transapical endocardial resynchronization therapy

Purpose: Cardiac resynchronization therapy (CRT) is an established therapeutic option in selected heart failure patients (pts). However, the transvenous left ventricular (LV) lead implantation remains ineffectual in a considerable number of pts. Transapical LV (TALV) lead implantation is an alternative minimally invasive, surgical, endocardial implantation technique. The aim of the present prospective study is to determine the long-term outcome, including the cerebral thromboembolic complications, of pts

Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

Major combined electrolyte deficiency during therapy with low-dose Cisplatin, 5-Fluorouracil and Interferon alpha: report on several cases and review of the literature [ISRCTN62866759]

BACKGROUND: Low-dose Cisplatin and Interferon alpha treatment of solid tumors rarely has been associated with severe hypocalcaemia. To the authors knowledge the phenomenon has not been reported previously in patients with pancreatic carcinoma. CASE PRESENTATION: A patient with resected adenocarcinoma of the pancreas was treated with adjuvant radio-chemo-immunotherapy using a combination of low-dose Cisplatin, 5-Fluorouracil and Interferon alpha together with external beam radiation. Severe hypocalcaemia without signs of acute renal failure or electrolyte disturbance occurred within 2 days at the 4th week of treatment and required intensive care treatment. CONCLUSION: Combination of biological and cytotoxic therapies may increase the incidence of severe hypocalcaemia in pancreatic cancer. Oncologists should remain attentive of this problem as more highly active regimes become available

Morphological evaluation of experimental autologous rectus fascia sheath vascular grafts used for arterial replacement in a dog model

Although experimental autologous patch or tubular conduit vascular grafts made from the internal rectus fascia sheath (IRFS) have been reported in the literature, thorough morphological evaluation and verification of the histological arterialisation of such grafts are lacking. Four purpose-bred Beagle dogs were utilised to create eight arterial internal rectus fascia sheath (ARFS) grafts implanted between bisected ends of the external iliac arteries. Four out of the eight ARFS grafts were patent after three months. Haematoxylin-eosin and Azan staining verified that the grafts gained a vessel-like layered structure with the presence of large amounts of collagen fibres. Although the inner surface of the intact IRFS was originally covered with claudin-5-negative and pancytokeratin-positive mesothelial cells in control samples, the internal cells of the ARFS grafts became claudin-5 positive and pancytokeratin negative like in intact arteries. Spindle-shaped cells of the wall of ARFS grafts were α-smooth muscle actin (α-SMA) positive just like the smooth muscle cells of intact arteries, but α-SMA immunoreactivity was negative in the intact IRFS. According to these findings, the fibroblast cells of the ARFS graft have changed into myofibroblast cells. The study has proved that ARFS grafts may be used as an alternative in arterial replacement, since the graft becomes morphologically and functionally similar to the host vessel via arterialisation

A new APE1/Ref-1-dependent pathway leading to reduction of NF-κB and AP-1, and activation of their DNA-binding activity

APE1/Ref-1 is thought to be a multifunctional protein involved in reduction–oxidation (redox) regulation and base excision DNA repair, and is required for early embryonic development in mice. APE1/Ref-1 has redox activity and AP endonuclease activity, and is able to enhance DNA-binding activity of several transcription factors, including NF-κB, AP-1 and p53, through reduction of their critical cysteine residues. However, it remains elusive exactly how APE1/Ref-1 carries out its essential functions in vivo. Here, we show that APE1/Ref-1 not only reduces target transcription factors directly but also facilitates their reduction by other reducing molecules such as glutathione or thioredoxin. The new activity of APE1/Ref-1, termed redox chaperone activity, is exerted at concentration significantly lower than that required for its redox activity and is neither dependent on its redox activity nor on its AP endonuclease activity. We also show evidence that redox chaperone activity of APE1/Ref-1 is critical to NF-κB-mediated gene expression in human cells and is mediated through its physical association with target transcription factors. Thus, APE1/Ref-1 may play multiple roles in an antioxidative stress response pathway through its different biochemical activities. These findings also provide new insight into the mechanism of intracellular redox regulation