Developmental functions of the P120-catenin sub-family

AbstractFor more than a decade, cell, developmental and cancer investigators have brought about a wide interest in the biology of catenin proteins, an attraction being their varied functions within differing cellular compartments. While the diversity of catenin localizations and roles has been intriguing, it has also posed a challenge to the clear interpretation of loss- or gain-of-function developmental phenotypes. The most deeply studied member of the larger catenin family is beta-catenin, whose contributions span areas including cell adhesion and intracellular signaling/ transcriptional control. More recently, attention has been directed towards p120-catenin, which in conjunction with the p120-catenin sub-family members ARVCF- and delta-catenins, are the subjects of this review. Although the requirement for vertebrate versus invertebrate p120-catenin are at variance, vertebrate p120-catenin sub-family members may each inter-link cadherin, cytoskeletal and gene regulatory functions in embryogenesis and disease

Complications of nephrotic syndrome

Nephrotic syndrome (NS) is one of the most common glomerular diseases that affect children. Renal histology reveals the presence of minimal change nephrotic syndrome (MCNS) in more than 80% of these patients. Most patients with MCNS have favorable outcomes without complications. However, a few of these children have lesions of focal segmental glomerulosclerosis, suffer from severe and prolonged proteinuria, and are at high risk for complications. Complications of NS are divided into two categories: disease-associated and drug-related complications. Disease-associated complications include infections (e.g., peritonitis, sepsis, cellulitis, and chicken pox), thromboembolism (e.g., venous thromboembolism and pulmonary embolism), hypovolemic crisis (e.g., abdominal pain, tachycardia, and hypotension), cardiovascular problems (e.g., hyperlipidemia), acute renal failure, anemia, and others (e.g., hypothyroidism, hypocalcemia, bone disease, and intussusception). The main pathomechanism of disease-associated complications originates from the large loss of plasma proteins in the urine of nephrotic children. The majority of children with MCNS who respond to treatment with corticosteroids or cytotoxic agents have smaller and milder complications than those with steroid-resistant NS. Corticosteroids, alkylating agents, cyclosporin A, and mycophenolate mofetil have often been used to treat NS, and these drugs have treatment-related complications. Early detection and appropriate treatment of these complications will improve outcomes for patients with NS

Non-practising entities (NPEs) and patent remedies for future infringement

This research establishes a new patent remedy (injunction) system against future infringements in such a way as to discourage trolling behaviours of non-practising entities (NPEs) without chilling inventors’ incentives to innovate. For this research target, this thesis reviewed the general characteristics of NPEs in the current and past patent system, the current patent remedy laws in different countries (the US, UK and Germany), the patent holdups caused by NPEs’ patent enforcement against manufacturers, and various solutions which have been proposed so far. In doing so, it addresses important findings that the major cause of NPE problems stems from the inherent uncertainty nature of patent, that the courts’ discretion of whether to grant or deny an injunction needs to be clearly defined, and that the new injunction system should skilfully balance the short-term as well as the long-term transaction costs which are caused by NPEs’ patent enforcements. Considering these findings, this thesis proposes a new injunction model, alias a ‘three-tiered remedy system.’ Unlike the present two-tiered system, it divides the remedies into three different types: (1) granting an unqualified injunction against wilful infringers; (2) granting a suspended injunction against innocent infringers; and (3) denying injunctions in exceptional circumstances. The most differentiated feature of this model is to award a suspended injunction as a default remedy in order to mitigate the patent holdup arising from the uncertainty problem of patent. Since the suspension period is determined in proportion to the required time for designing around the infringed patent, this new model can provide a very useful solution to mitigate the harmful effect of NPEs’ patent enforcement without jeopardizing the integrity of exclusive right of patent at the same time

Non-practising entities (NPEs) and patent remedies for future infringement

This research establishes a new patent remedy (injunction) system against future infringements in such a way as to discourage trolling behaviours of non-practising entities (NPEs) without chilling inventors’ incentives to innovate. For this research target, this thesis reviewed the general characteristics of NPEs in the current and past patent system, the current patent remedy laws in different countries (the US, UK and Germany), the patent holdups caused by NPEs’ patent enforcement against manufacturers, and various solutions which have been proposed so far. In doing so, it addresses important findings that the major cause of NPE problems stems from the inherent uncertainty nature of patent, that the courts’ discretion of whether to grant or deny an injunction needs to be clearly defined, and that the new injunction system should skilfully balance the short-term as well as the long-term transaction costs which are caused by NPEs’ patent enforcements. Considering these findings, this thesis proposes a new injunction model, alias a ‘three-tiered remedy system.’ Unlike the present two-tiered system, it divides the remedies into three different types: (1) granting an unqualified injunction against wilful infringers; (2) granting a suspended injunction against innocent infringers; and (3) denying injunctions in exceptional circumstances. The most differentiated feature of this model is to award a suspended injunction as a default remedy in order to mitigate the patent holdup arising from the uncertainty problem of patent. Since the suspension period is determined in proportion to the required time for designing around the infringed patent, this new model can provide a very useful solution to mitigate the harmful effect of NPEs’ patent enforcement without jeopardizing the integrity of exclusive right of patent at the same time

The Light and Period Variations of the Eclipsing Binary AA Ursae Majoris

We present new multiband CCD photometry for AA UMa made on 8 nights between January and March 2009; the $R$ light curves are the first ever compiled. Historical light curves, as well as ours, display partial eclipses and inverse O'Connell effects with Max I fainter than Max II. Among possible spot models, a cool spot on either of the component stars and its variability with time permit good light-curve representations for the system. A total of 194 eclipse timings over 81 yrs, including our five timings, were used for ephemeris computations. We found that the orbital period of the system has varied due to a periodic oscillation overlaid on an upward parabolic variation. The continuous period increase at a fractional rate of $+$1.3$\times$10$^{-10}$ is consistent with that calculated from the W-D code and can be interpreted as a thermal mass transfer from the less to the more massive secondary star at a rate of 6.6$\times$10$^{-8}$ M$_\odot$ yr$^{-1}$. The periodic component is in satisfactory accord with a light-time effect due to an unseen companion with a period of 28.2 yrs, a semi-amplitude of 0.007 d, and a minimum mass of $M_3 \sin i_3$=0.25 $M_\odot$ but this period variation could also arise from magnetic activity.Comment: 23 pages, including 5 figures and 8 tables, accepted for publication in PAS

Numerical Analysis of Saturated Sand Under Dynamic Loads

In this study, the behavior of reclaimed soils including the effects of excess pore water pressure and the loss of strength under dynamic loads or earthquakes are investigated and simulated. The constitutive model based on the disturbed state concept (DSC) is introduced and DSC-DYN2D program is utilized in a numerical analysis. In the laboratory test, quasi-static and cyclic triaxial tests were carried out to determine parameters for the numerical analysis. Field tests were executed in Inchon International Airport with a 10 tons hydraulic hammer. In the field test, the data of dynamic loads and excess pore water pressure were measured using a 3-D geophone and a pressure transducer respectively, The data of field tests showed the accumulation of excess pore water pressure when rapid dynamic loads were applied. Especially, a back-prediction program based on DSC model is developed and verified its accuracy using various parameters from the cyclic triaxial test. As the results of numerical simulation, the predicted trends for excess pore water pressure compare well with the observed data. Based on the result of this research, it is found that the numerical analysis based on the DSC model is compatible to predict the softening behavior of saturated reclaimed soils under dynamic loads

Wnt signaling in liver regeneration, disease, and cancer

The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. In this review, we discussed the role of Wnt signaling in liver regeneration, precancerous lesion, and liver cancer. Furthermore, we summarized the basic and clinical approaches of Wnt signaling blockade and proposed the therapeutic prospects of cancer-specific Wnt signaling blockade for liver cancer treatment

Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer

Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic pig's ear cells compared with that in normal minipig fetal fibroblasts. Our data indicate that grafts of transgenic pigs expressing membrane-bound human FasL control the cellular immune response to xenografts, creating a window of opportunity to facilitate xenograft survival

Inflammation and hyponatremia: an underrecognized condition?

Timely diagnosis of hyponatremia is important for preventing potential morbidity and mortality as it is often an indicator of underlying disease. The most common cause of eurvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recent studies have demonstrated that proinflammatory cytokines such as interleukin (IL) 1β and IL-6 are involved in the development of hyponatremia, a condition that is associated with severe inflammation and is related to antidiuretic hormone (ADH) secretion. Serum sodium levels in hyponatremia are inversely correlated with the percentage of neutrophils, C-reactive protein, and N-terminal-pro brain type natriuretic peptide. Additionally, elevated levels of serum IL-6 and IL-1β are found in inflammatory diseases, and their levels are higher in patients with hyponatremia. Because it is significantly correlated with the degree of inflammation in children, hyponatremia could be used as a diagnostic marker of pediatric inflammatory diseases. Based on available evidence, we hypothesize that hyponatremia may be associated with inflammatory diseases in general. Understanding the mechanisms responsible for augmented ADH secretion during inflammation, monitoring patient sodium levels, and selecting the appropriate intravenous fluid treatment are important components that may lower the morbidity and mortality of patients in a critical condition