Growth factors in idiopathic pulmonary fibrosis: relative roles

Treatment of idiopathic pulmonary fibrosis patients has evolved very slowly; the fundamental approach of corticosteroids alone or in combination with other immunosuppressive agents has had little impact on long-term survival. The continued use of corticosteroids is justified because of the lack of a more effective alternative. Current research indicates that the mechanisms driving idiopathic pulmonary fibrosis reflect abnormal, dysregulated wound healing within the lung, involving increased activity and possibly exaggerated responses by a spectrum of profibrogenic growth factors. An understanding of the roles of these growth factors, and the way in which they modulate events at cellular level, could lead to more targeted therapeutic strategies, improving patients' quality of life and survival

Pathogenicity of anti-ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura.

BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease in which anti-ADAMTS13 autoantibodies cause severe enzyme deficiency. ADAMTS13 deficiency causes the loss of regulation of von Willebrand factor multimeric size and platelet-tethering function, which results in the formation of disseminated microvascular platelet microthrombi. Precisely how anti-ADAMTS13 autoantibodies, or antibody subsets, cause ADAMTS13 deficiency (ADAMTS13 activity generally < 10%) has not been formally investigated. METHODS: We analysed 92 acquired TTP episodes at presentation, through treatment and remission/relapse using epitope mapping and functional analyses to understand the pathogenic mechanisms of anti-ADAMTS13 IgG. RESULTS: 89/92 of TTP episodes had IgG recognising the ADAMTS13 N-terminal domains. The central spacer domain was the only N-terminal antigenic target detected. 38/92 TTP episodes had autoantibodies recognising the N-terminal domains alone; 54/92 TTP episodes also had antibodies against the ADAMTS13 C-terminal domains (TSP2-8 and/or CUB domains). Changes in autoantibody specificity were detected in 9/16 patients at relapse, suggesting a continued development of the disease. Functional analyses on IgG from 43 patients revealed inhibitory IgG were limited to anti-spacer domain antibodies. However, 15/43 patients had autoantibodies with no detectable inhibitory action and as many as 32/43 patients had autoantibodies with inhibitory function that was insufficient to account for the severe deficiency state, suggesting that in many patients there is an alternative pathogenic mechanism. We therefore analysed plasma ADAMTS13 antigen levels in 91 acquired TTP presentation samples. We demonstrated markedly reduced ADAMTS13 antigen levels in all presentation samples, median 6% normal (range 0-47%), with 84/91 patients having < 25% ADAMTS13 antigen. ADAMTS13 antigen in the lowest quartile at first presentation was associated with increased mortality (odds ratio 5.7). CONCLUSIONS: Anti-spacer domain autoantibodies are the major inhibitory antibodies in acquired TTP. However, depletion of ADAMTS13 antigen (rather than enzyme inhibition) is a dominant pathogenic mechanism. ADAMTS13 antigen levels at presentation have prognostic significance. Taken together, our results provide new insights into the pathophysiology of acquired TTP

Anatomical features and cell-cell interactions in the human limbal epithelial stem cell niche

Epithelial stem cells of the ocular surface are essential for the maintenance of corneal transparency and therefore for vision. Human corneal/limbal epithelial stem cells (LESCs) are believed to reside in the limbus, the interface between the peripheral cornea and neighboring conjunctiva. A specific anatomical microenvironment called the niche regulates the proliferative and differentiation potential of LESCs and their daughter cells. This review covers multiple structural and functional aspects of the human limbal epithelial stem cell niche, including: anatomical features of the niche, composition of the local extracellular matrix, soluble factors and signaling pathways, cell-to-cell interactions with surrounding stromal niche cells and melanocytes

The Role of Head Teacher in Improvisation and Maintenance of School Plants

The conditions and situation of the physical and infrastructural facilities in the primary schools had marred the attainment of the goal of education for all. The present Primary Education Commission (UPEC) 1999/91 survey indicated that approximately 4.9% of Nigerian primary school have no building, while the survey equally shows that the is a short fall of 64.2% in pupils furniture and 62.5% in teachers' and non teaching furniture, nationwide. It also stressed further that equipment for teaching sciences, sports, Home Economics creative Arts were lacking in majority of the Primary Schools. Moreover, the above situations seem not to have improved in the recent times. Many of the primary school buildings are dilapidated, displaying no window panes or Shutters, no ceilings, plaster peel offs, broken floors and leaking roofs. Poor as these structures are, they are not even adequate and thus two or more streams have to use the same dilapidated class in many cases. This has resulted into overcrowded classrooms with serious implications for teaching and learning in the primary schools in Nigeria. It is against this backdrop that this paper examines the role of head teacher in improvisation and maintenance of school plants in primary schools.Keywords: Primary Education, Head Teacher, School Plants, Physical facilities and infrastructural facilitie

A compact HF/UHF dual band RFID tag antenna

This paper presents a novel dual band RFID (radio frequency identification) tag antenna. Two challenges are faced: the compact dimension and the impaired bandwidth due to the couplings between two band structures. A spiral coil is designed to handle the HF (13.56MHz) near field coupling, and a diagonal symmetric design consisting of two meander lines are placed inside the coil for UHF band (915MHz). This structure supports multiple resonance modes around 915MHz to broaden the working bandwidth under the large inductive circumstance from the HF coil. The proposed antenna is easy to adjust by both coarse tuning and fine tuning. Its overall dimension is of a credit card size on a single layer thin substrate. © 2013 IEEE.published_or_final_versio

Ion Larmor radius effects near a reconnection X line at the magnetopause: THEMIS observations and simulation comparison

We report a Time History of Events and Macroscale Interactions during Substorms (THEMIS-D) spacecraft crossing of a magnetopause reconnection exhaust ~9 ion skin depths (di) downstream of an X line. The crossing was characterized by ion jetting at speeds substantially below the predicted reconnection outflow speed. In the magnetospheric inflow region THEMIS detected (a) penetration of magnetosheath ions and the resulting flows perpendicular to the reconnection plane, (b) ion outflow extending into the magnetosphere, and (c) enhanced electron parallel temperature. Comparison with a simulation suggests that these signatures are associated with the gyration of magnetosheath ions onto magnetospheric field lines due to the shift of the flow stagnation point toward the low-density magnetosphere. Our observations indicate that these effects, ~2–3 di in width, extend at least 9 di downstream of the X line. The detection of these signatures could indicate large-scale proximity of the X line but do not imply that the spacecraft was upstream of the electron diffusion region

Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy

Post-transplant lymphomas or other lymphoproliferative lesions, which were usually associated with Epstein-Barr virus infections, developed in 8, 4, 3, and 2 recipients, respectively, of cadaveric kidney, liver, heart, and heart-lung homografts. Reduction or discontinuance of immunosuppression caused regression of the lesions, often without subsequent rejection of the grafts. Chemotherapy and irradiation were not valuable. The findings may influence policies about treating other kinds of post-transplantation neoplasms

Oral Mucosa Tissue Equivalents for the Treatment of Limbal Stem Cell Deficiency

Cultured limbal and oral epithelial cells have been successfully used to treat patients with limbal stem cell deficiency (LSCD). The most common culture method for these cell therapies utilizes amniotic membrane as a cell support and/or murine 3T3s as feeder fibroblasts. The aim of this study is to refine the production of autologous oral mucosal cell therapy for the treatment of LSCD. Real architecture for 3D tissue (RAFT) is used as an alternative cell culture support. In addition, oral mucosal cells (epithelial and fibroblast) are used as autologous alternatives to donor human limbal epithelial cells (HLE) and murine 3T3s. The following tissue equivalents are produced and characterized: first, for patients with bilateral LSCD, an oral mucosa tissue equivalent consisting of human oral mucosal epithelial cells on RAFT supported by human oral mucosal fibroblasts (HOMF). Second, for patients with unilateral LSCD, HLE on RAFT supported by HOMF. For both tissue equivalent types, features of the cornea are observed including a multi-layered epithelium with small cells with a stem cell like phenotype in the basal layer and squamous cells in the top layers, and p63α and PAX6 expression. These tissue equivalents may therefore be useful in the treatment of LSCD

Reduced performance of native infauna following recruitment to a habitat-forming invasive marine alga

Despite well-documented negative impacts of invasive species on native biota, evidence for the facilitation of native organisms, particularly by habitat-forming invasive species, is increasing. However, most of these studies are conducted at the population or community level, and we know little about the individual fitness consequences of recruitment to habitat-forming invasive species and, consequently, whether recruitment to these habitats is adaptive. We determined the consequences of recruitment to the invasive green alga Caulerpa taxifolia on the native soft-sediment bivalve Anadara trapezia and nearby unvegetated sediment. Initially, we documented the growth and survivorship of A. trapezia following a natural recruitment event, to which recruitment to C. taxifolia was very high. After 12 months, few clams remained in either habitat, and those that remained showed little growth. Experimental manipulations of recruits demonstrated that all performance measures (survivorship, growth and condition) were significantly reduced in C. taxifolia sediments compared to unvegetated sediments. Exploration of potential mechanisms responsible for the reduced performance in C. taxifolia sediments showed that water flow and water column dissolved oxygen (DO) were significantly reduced under the canopy of C. taxifolia and that sediment anoxia was significantly higher and sediment sulphides greater in C. taxifolia sediments. However, phytoplankton abundance (an indicator of food supply) was significantly higher in C. taxifolia sediments than in unvegetated ones. Our results demonstrate that recruitment of native species to habitat-forming invasive species can reduce growth, condition and survivorship and that studies conducted at the community level may lead to erroneous conclusions about the impacts of invaders and should include studies on life-history traits, particularly juveniles. © 2008 Springer-Verlag

AdaSampling for positive-unlabeled and label noise learning with bioinformatics applications

© 2018 IEEE. Class labels are required for supervised learning but may be corrupted or missing in various applications. In binary classification, for example, when only a subset of positive instances is labeled whereas the remaining are unlabeled, positive-unlabeled (PU) learning is required to model from both positive and unlabeled data. Similarly, when class labels are corrupted by mislabeled instances, methods are needed for learning in the presence of class label noise (LN). Here we propose adaptive sampling (AdaSampling), a framework for both PU learning and learning with class LN. By iteratively estimating the class mislabeling probability with an adaptive sampling procedure, the proposed method progressively reduces the risk of selecting mislabeled instances for model training and subsequently constructs highly generalizable models even when a large proportion of mislabeled instances is present in the data. We demonstrate the utilities of proposed methods using simulation and benchmark data, and compare them to alternative approaches that are commonly used for PU learning and/or learning with LN. We then introduce two novel bioinformatics applications where AdaSampling is used to: 1) identify kinase-substrates from mass spectrometry-based phosphoproteomics data and 2) predict transcription factor target genes by integrating various next-generation sequencing data