Smith Predictor Sliding Mode Closed-loop Glucose Controller in Type 1 Diabetes

Type 1 diabetic patients depend on external insulin delivery to keep their blood glucose within near-normal ranges. In this work, two robust closed-loop controllers for blood glucose regulation are developed to prevent the life-threatening hypoglycemia, as well as to avoid extended hyperglycemia. The proposed controllers are designed by using the sliding mode control technique in a Smith predictor structure. To improve meal disturbance rejection, a simple feedforward controller is added to inject meal-time insulin bolus. Simulations scenarios were used to test the controllers, and showed the controllers ability to maintain the glucose levels within the safe limits in the presence of errors in measurements, modeling and meal estimation

A Gain Scheduling Model Predictive Controller for Blood Glucose Control in Type 1 Diabetes

This paper presents a control strategy for blood glucose(BG) level regulation in type 1 diabetic patients. To design the controller, model-based predictive control scheme has been applied to a newly developed diabetic patient model. The controller is provided with a feedforward loop to improve meal compensation, a gain-scheduling scheme to account for different BG levels, and an asymmetric cost function to reduce hypoglycemic risk. A simulation environment that has been approved for testing of artificial pancreas control algorithms has been used to test thecontroller. The simulation results show a good controller performance in fasting conditions and meal disturbance rejection, and robustness against model–patient mismatch and errors in mealestimation

Minor salivary gland tumors: a clinicopathological study of 18 cases

Introduction: Minor salivary gland tumors (MSGTs) are infrequent, representing 10-15% of all salivary neoplasms. Despite this low frequency, MSGTs conform a heterogeneous group of neoplasms characterized by a broad range of histological types. Patients and method: We identified cases of MSGT in a retrospective study of the biopsies made in the period 1997-2007 in the Service of Oral Surgery (Dental Clinic of the University of Barcelona, Spain). The data collected comprised patient age and sex, the clinical characteristics and location of the tumor, the duration of the lesion, its size, the treatment provided, and the histopathological findings. Results: Of the 18 cases of MSGT studied, 12 corresponded to women (66.7%) and 6 to men (33.3%). The great majority (94.4%) were benign tumors. The preferential location was the posterior third of the hard palate (33.2%), followed by the soft palate (16.7%) and the mucosa of the upper lip (16.7%). The histopathological diagnoses of our MSGTs comprised 10 pleomorphic adenomas (55.3%), 2 cystadenomas (11.1%), 1 myoepithelioma (5.6%), 1 sialadenoma papilliferum (5.6%), 1 basal cell adenoma (5.6%), 1 Warthin"s tumor (5.6%), 1 canalicular adenoma (5.6%), and 1 low-grade polymorphic adenocarcinoma (5.6%). Discussion and conclusions: Coinciding with our own results, the literature describes a high recurrence rate for MSGTs (5-30%) when surgical removal is incomplete. Six percent of all benign minor salivary gland tumors are considered to relapse, versus 65% of all malignant lesions. Periodic clinical controls are required, since the possibility of malignant transformation must be taken into account

A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques

Background: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs. Methods: To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1. Results: Our approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4+ and CD8+ T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4+ and CD8+ T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ+ CD8+ T cells being Granzyme B+ and able to degranulate (CD107a+). Conclusions: These data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants.

Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of a2b1 Integrin and E-Cadherin Function

In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLex) along with a concomitant decrease in α2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, α2β1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLex and lower α2,6-sialic acid content on the glycans of their α2β1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLex and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion