Fatty acid derivatised analogues of glucose-dependent insulinotropic polypeptide with improved antihyperglycaemic and insulinotropic properties

C-terminal acylation of Lys(37) with myristic (MYR; tetradecanoic acid), palmitic (PAL; hexadecanoic acid) and stearic (octadecanoic acid) fatty acids with or without N-terminal acetylation was employed to develop long-acting analogues of the glucoregulatory hormone, glucose-dependent insulinotropic polypeptide (GIP). All GIP analogues exhibited resistance to dipeptidylpeptidase-IV (DPP-IV) and significantly improved in vitro cAMP production and insulin secretion. Administration of GIP analogues to ob/ob mice significantly lowered plasma glucose-GIP(Lys(37)MYR), N-AcGIP(Lys(37)MYR) and GIP(Lys(37)PAL) increased plasma insulin concentrations. GIP(Lys(37)MYR) and N-AcGIP(Lys(37)MYR) elicited protracted glucose-lowering effects when administered 24h prior to an intraperitoneal glucose load. Daily administration of GIP(Lys(37)MYR) and N-AcGIP(Lys(37)MYR) to ob/ob mice for 24 days decreased glucose and significantly improved plasma insulin, glucose tolerance and beta-cell glucose responsiveness. Insulin sensitivity, pancreatic insulin content and triglyceride levels were not changed. These data demonstrate that C-terminal acylation particularly with myristic acid provides a class of stable, longer-acting forms of GIP for further evaluation in diabetes therapy.

GIP(Lys16PAL) and GIP(LyS37PAL):novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potentia

Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys16PAL) and GIP(Lys37PAL) were resistant to dipeptidyl peptidase IV (DPP IV) degradation. In vitro studies demonstrated that GIP analogues retained their ability to activate the GIP receptor through production of cAMP and to stimulate insulin secretion. Intraperitoneal administration of GIP analogues to obese diabetic (ob/ob) mice significantly decreased the glycemic excursion and elicited increased and prolonged insulin responses compared to native GIP. A protracted glucose-lowering effect was observed 24 h following GIP(Lys37PAL) administration. Once a day injection for 14 days decreased nonfasting glucose, improved glucose tolerance, and enhanced the insulin response to glucose. These data demonstrate that fatty acid derivatized GIP peptides represent a novel class of long-acting stable GIP analogues for therapy of type 2 diabetes. © 2006 American Chemical Society.

Situational Script Management of Business Processes with Changeable Structure

In the presented work the problem of management business-processes with changeable structure is considered and situational based approach to its decision is offered. The approach is based on situational model of management business-process according to which process is represented as a set of situations. The script defining necessary actions is connected with each situation. Management of process is carried out by means of the rules formalizing functional requirements to processes.

Using Inside-Outside Algorithm for Estimation of the Offspring Distribution in Multitype Branching Processes

Multitype branching processes (MTBP) model branching structures, where the nodes of the resulting tree are particles of different types. Usually such a process is not observable in the sense of the whole tree, but only as the “generation” at a given moment in time, which consists of the number of particles of every type. This requires an EM-type algorithm to obtain a maximum likelihood (ML) estimate of the parameters of the branching process. Using a version of the inside-outside algorithm for stochastic context-free grammars (SCFG), such an estimate could be obtained for the offspring distribution of the process.

On the Extinction Probability for Bisexual Branching Processes in Varying Environments

2000 Mathematics Subject Classification: 60J80

Large Deviations and Branching Processes

These lecture notes are devoted to present several uses of Large Deviation asymptotics in Branching Processes.

Em Estimation of the Offspring Distribution in Mutitype Branching Processes - a Model in Cell Kinetics

2000 Mathematics Subject Classification: 60J80, 60J85, 62P10, 92D25.

Subcritical Randomly Indexed Branching Processes

2000 Mathematics Subject Classification: 60J80, 62P05.

Some Bounds for Almost Absorbing Birth and Death Processes with Catastrophes

2000 Mathematics Subject Classification: 60J27.

Characterization of Schrödinger Processes with Unbounded Potentials

2000 Mathematics Subject Classification: 49L20, 60J60, 93E20

Estimation of the Offspring Mean in a General Single-Type Size-Dependent Branching Process

2000 Mathematics Subject Classification: 60J80, 62F12, 62P10

A linear relational DEA model to evaluate two-stage processes with shared inputs

Two-stage data envelopment analysis (DEA) efficiency models identify the efficient frontier of a two-stage production process. In some two-stage processes, the inputs to the first stage are shared by the second stage, known as shared inputs. This paper proposes a new relational linear DEA model for dealing with measuring the efficiency score of two-stage processes with shared inputs under constant returns-to-scale assumption. Two case studies of banking industry and university operations are taken as two examples to illustrate the potential applications of the proposed approach.

Logisztikai folyamatok informatikai támogatottsága Magyarországon – fókuszban a disztribúciós logisztika = Backing logistics processes with information technology – current practice and improvement possibilities at Hungarian companies

Az elemzés egy, a Budapesti Corvinus Egyetem (BCE) Logisztika és Ellátási Lánc Menedzsment Tanszéke által végzett kérdőíves felmérés eredményeit foglalja össze. A kutatás alapvető célja, hogy felmérje és bemutassa a hazai vállalatok logisztikai, ezen belül is elsősorban disztribúciós logisztikai folyamatainak informatikai oldalról történő jelenlegi támogatottsági szintjét és a következő két-három év e téren várható fejlesztési irányait. A kutatás szisztematikusan kitért a logisztikai információs rendszer valamennyi alrendszerére, vizsgálta a különböző azonosítási megoldások elterjedtségét, a vállalatirányítási rendszer, illetve egyes moduljainak használatával kapcsolatban kialakult gyakorlatot, de a logisztika stratégiai döntéseinek informatikai támogatottságát és a használt kommunikációs technikákat is. Összességében megállapíthatjuk, hogy a logisztikai információs rendszerek fejlettségi szintje ma Magyarországon közepesnek mondható, fontos megjegyezni azonban, hogy a KKV szektor e téren is jelentős lemaradással rendelkezik. Ez természetesen azt is jelent, hogy az informatikai eszközök alkalmazásának kiterjesztésével még jelentős teljesítményjavulás érhető el. = The essay summarizes the results of a survey carried out by Corvinus University of Budapest, Department of Logistics and Supply Chain Management. Aim of the survey was to analyze and describe the actual Hungarian company practice regarding the IT support of logistics – and particularly distribution – processes, and the plans of developing it within the next 2-3 years. Survey has systematically covered all fields of logistics information system, analyzed the prevalence of different identification techniques and systems. On the whole we appoint that logistics information systems applied by Hungarian companies are on satisfactory level; however it is important to tell that SME companies are in huge lag. This means that improving logistics information system hides the possibility of considerable performance development.

Dealing with Immigration in the Context of EU Enlargement: the Case of Transitional Provisions

This analysis addresses the issue of immigration in the context of the European Union enlargement. Focusing on the use of transitional provisions, it attempts to explain why and when EU leaders give workers from new member countries access to their labor market. Building on the observation that EU leaders seem not to use provisions in the spirit of the law, I gauge the importance of domestic political stakes in the use of those provisions. The empirical results suggest that although EU leaders implement and repeal provisions based on economic circumstances, political factors do intervene in the decision-making process. However, it remains uncertain whether those political factors are institutional or purely electoral.