Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase

The first study purpose was to investigate the glucose dependency of arginine vasopressin (AVP)-induced insulin, glucagon and somatostatin release from the perfused rat pancreas. AVP (30 or 300 pmol/L) was tested in the presence of glucose concentrations of 0, 1.4, 5.5 (basal level), or 20 mmol/L. The findings from this study suggested that AVP may increase insulin and glucagon release by a direct action on beta- and alpha-cells, respectively. These increases are glucose-dependent; the higher the glucose concentration, the greater the enhancement of AVP-induced insulin release. In contrast, the lower the glucose concentration, the greater the enhancement of AVP-induced glucagon release. AVP not only can enhance glucose-induced insulin release, but also can initiate insulin release. alpha-cells are much more sensitive to AVP than beta-cells in hormone release. Furthermore, our results confirmed the previous findings that hypoglycemia directly increases glucagon and decreases insulin release.;The second study purpose was to characterize the mechanisms by which cAMP/PKA enhances AVP-induced glucagon release and provide further details in the intracellular molecular components involved in this enhancement, particularly at the level of exocytosis. Increasing intracellular cAMP levels by forskolin or IBMX enhanced AVP-induced glucagon release from the perfused rat pancreas and the clonal alpha-cells InR1G9. cAMP/PKA did not increase [Ca 2+]i nor did it;enhance AVP-induced [Ca2+]i increase. Forskolin and IBMX enhanced AVP-induced glucagon release in Ca2+-containing but not in Ca2+-free medium. InR1G9 cells were loaded with styryl dye FM1-43 to measure the size of readily releasable pool (RRP). The combination of AVP and forskolin induced higher increase in fluorescence intensity than AVP or forskolin alone, which reflects an increase in the size of the RRP. Secretory granules in the reserve pool (RP) are thought to be reversibly connected to the actin-based cytoskeleton by synapsin I. Pretreatment with antisynapsin I antibody abolished the effect of forskolin/AVP-induced glucagon release. In addition, FM1-43 loading experiments showed that synapsin I is involved in recruitment of secretory granules from RP to RRP. Our results suggested that cAMP, acting through PKA, increases the number of secretory granules in the RRP by mobilization of granules from the RP, an action mediated by synapsin I

RCCNet: An Efficient Convolutional Neural Network for Histological Routine Colon Cancer Nuclei Classification

Efficient and precise classification of histological cell nuclei is of utmost importance due to its potential applications in the field of medical image analysis. It would facilitate the medical practitioners to better understand and explore various factors for cancer treatment. The classification of histological cell nuclei is a challenging task due to the cellular heterogeneity. This paper proposes an efficient Convolutional Neural Network (CNN) based architecture for classification of histological routine colon cancer nuclei named as RCCNet. The main objective of this network is to keep the CNN model as simple as possible. The proposed RCCNet model consists of only 1,512,868 learnable parameters which are significantly less compared to the popular CNN models such as AlexNet, CIFARVGG, GoogLeNet, and WRN. The experiments are conducted over publicly available routine colon cancer histological dataset "CRCHistoPhenotypes". The results of the proposed RCCNet model are compared with five state-of-the-art CNN models in terms of the accuracy, weighted average F1 score and training time. The proposed method has achieved a classification accuracy of 80.61% and 0.7887 weighted average F1 score. The proposed RCCNet is more efficient and generalized terms of the training time and data over-fitting, respectively.Comment: Published in ICARCV 201

Supercritical heat transfer characteristics of couple stress convection flow from a vertical cylinder using an equation of state approach

The present work describes numerical simulations of the supercritical heat transfer characteristics of couple stress fluid flow from a vertical cylinder using the equation of state approach. Redlich-Kwong (RK-EOS) and Van der Waals (VW-EOS) equations of state (EOS) are deployed to derive the equation for the thermal expansion coefficient (β). The β values calculated based on RK-EOS are sufficiently close to the experimental values when compared with those based on VW-EOS. Due to the presence of couple stresses in the fluid, highly nonlinear coupled partial differential equations are generated. These primitive equations are reduced to dimensionless form by using suitable non-dimensional quantities. An unconditionally stable finite difference technique is used to solve the normalized conservation equations under physically viable boundary conditions, in order to describe the natural convection heat transfer characteristics of couple stress fluid external to a vertical cylinder in the supercritical region. For different values of the emerging physical parameters, numerical data for couple stress fluid for the case of Nitrogen is generated and presented in the form of graphs and tables. The present computations indicate that the velocity field is suppressed close to the cylinder whereas it is enhanced away from the cylinder with increasing values of reduced temperature in the supercritical fluid region. The reverse behavior is observed for reduced pressure. The present results are compared with the previous results and found to be in good agreement. Applications of the model include super-critical coating dynamics in the aerospace and medical industries

Mixed convective flow of a Casson fluid over a vertical stretching sheet

A coupled nonlinear boundary value problem arising from a mixed convective flow of a non-Newtonian fluid at a vertical stretching sheet with variable thermal conductivity is investigated in this paper. Casson fluid model is used to describe the non-Newtonian fluid behavior. Using a similarity transformation, the governing equations are transformed into a system of coupled, nonlinear ordinary differential equations and the analytical solutions for the velocity and temperature fields are obtained via a semi-analytical algorithm based on the optimal homotopy analysis method. To validate the method, comparisons are made with the available results in the literature for some special cases and the results are found to be in excellent agreement. The characteristics of the velocity and the temperature fields in the boundary layer have been analyzed for several sets of values of the Casson parameter, the Prandtl number, the temperature dependent thermal conductivity parameter, the velocity exponent parameter and the mixed convection parameter. The presented results through graphs and tables reveal substantial effects of the pertinent parameters on the flow and heat transfer characteristics. Furthermore, an error analysis is offered using an exact residual error and average residual error methods.postprin

Clinical outcome of combined scaphocapitate fusion and posterior interosseous neurectomy for stage III Kienbock’s disease

Background: Treatment of Kienbock’s disease is still controversial. Several authors have described various surgical treatment options for Kienbock’s disease, all of whom reported successful treatment outcomes. The purpose of this study is to explore the clinical results of posterior interosseous neurectomy and scaphocapitate fusion as a treatment option for stage III Kienbock’s disease.Methods: This study evaluated the range of motion, grip and functional results after treatment of ten wrists of stage III Kienbock’s disease. Four males and six females with average age of 26.3 years, seven dominant and three non-dominant wrists were included. Two patients were smokers while six were housewives, three manual workers and a lawyer. The average follow up period was 14.2 months.Results: Four patients revealed excellent, three good and three fair results. The mean modified Mayo score was 81.5. Flexion-extension range was 105.5° representing 74.9% of the contralateral side range. The mean flexion and extension range of operated side was increased, while the flexion increase was nonsignificant. Regarding radial-ulnar deviation, the mean range was 33.5° representing 76.5% of the contralateral side. The mean ulnar and radial deviation was increased, while the radial increase was nonsignificant. The mean grip strength was significantly increased to 90 mmHg representing 93.2% of the contralateral side.Conclusions: Scaphocpitate fusion is a recommended solution for treatment of late stages of Kienbock’s disease with lunate collapse. Longer postoperative time has a positive impact on grip strength and flexion-extension range of motion

Generalization of Fuzzy C-Means Based on Neutrosophic Logic

This article presents a New Neutrosophic C-Means (NNCMs) method for clustering. It uses the neutrosophic logic (NL), to generalize the Fuzzy C-Means (FCM) clustering system. The NNCMs system assigns objects to clusters using three degrees of membership: a degree of truth, a degree of indeterminacy, and a degree of falsity, rather than only the truth degree used in the FCM. The indeterminacy degree, in the NL, helps in categorizing objects laying in the intersection and the boundary areas. Therefore, the NNCMs reaches more accurate results in clustering. These degrees are initialized randomly without any constraints. That is followed by calculating the clusters’ centers

Neutrosophic rule-based prediction system for toxicity effects assessment of biotransformed hepatic drugs

Measuring toxicity is an important step in drug development. However, the current experimental meth- ods which are used to estimate the drug toxicity are expensive and need high computational efforts. Therefore, these methods are not suitable for large-scale evaluation of drug toxicity. As a consequence, there is a high demand to implement computational models that can predict drug toxicity risks. In this paper, we used a dataset that consists of 553 drugs that biotransformed in the liver

Angiogenesis: An update and potential drug approaches

The therapeutic potential of targeting tumor endothelium and vascular supply is now widely recognized to treat different diseases. One such disease is cancer; where endothelial cells are actively proliferating to support the tumor growth. Solid tumors cannot grow beyond the size of a few millimeters without inducing the proliferation of endothelium and formation of new blood vessels. Hence it is crucial to search for new agents that selectively block tumor blood supply. These include anti-angiogenic molecules, vascular disrupting agents or endothelial disrupting agents. The anti-angiogenic molecules such as monoclonal antibodies and tyrosine kinase inhibitors disrupt endothelial cell survival mechanisms and new blood vessel formation, and vascular disrupting agents for instance ligand-directed and small molecules can be used to disrupt the already existing abnormal vasculature that support tumors by targeting their dysmorphic endothelial cells. The recent advances in this area of research have identified a variety of investigational agents which are currently in clinical development at various stages and some of these candidates are already approved in cancer treatment. This report will review some of the recent developments and most significant advances in this field and outline future challenges and directions