Synthesis and evaluation of AKR1C inhibitory properties of A-ring halogenated oestrone derivatives

Enzymes AKR1C regulate the action of oestrogens, androgens, and progesterone at the pre-receptor level and are also associated with chemo-resistance. The activities of these oestrone halides were investigated on recombinant AKR1C enzymes. The oestrone halides with halogen atoms at both C-2 and C-4 positions (13β-, 13α-methyl-17-keto halogen derivatives) were the most potent inhibitors of AKR1C1. The lowest IC(50) values were for the 13α-epimers 2_2I,4Br and 2_2I,4Cl (IC(50), 0.7 μM, 0.8 μM, respectively), both of which selectively inhibited the AKR1C1 isoform. The 13α-methyl-17-keto halogen derivatives 2_2Br and 2_4Cl were the most potent inhibitors of AKR1C2 (IC(50), 1.5 μM, 1.8 μM, respectively), with high selectivity for the AKR1C2 isoform. Compound 1_2Cl,4Cl showed the best AKR1C3 inhibition, and it also inhibited AKR1C1 (Ki: AKR1C1, 0.69 μM; AKR1C3, 1.43 μM). These data show that halogenated derivatives of oestrone represent a new class of potent and selective AKR1C inhibitors as lead compounds for further optimisations

Confirmation of ovulation from urinary progesterone analysis: assessment of two automated assay platforms

Urinary concentrations of the major progesterone (P4) metabolite pregnanediol-3-glucuronide (PDG) are used to confirm ovulation. We aimed to determine whether automated immunoassay of urinary P4 was as efficacious as PDG to confirm ovulation. Daily urine samples from 20 cycles in 14 healthy women in whom ovulation was dated by ultrasound, and serial weekly samples from 21 women in whom ovulation was unknown were analysed. Daily samples were assayed by two automated P4 immunoassays (Roche Cobas and Abbott Architect) and PDG ELISA. Serial samples were assayed for P4 by Architect and PDG by ELISA. In women with detailed monitoring of ovulation, median (95% CI) luteal phase increase was greatest for PDG, 427% (261–661), 278% (187–354) for P4 Architect and least for P4 Cobas, 146% (130–191), p 0.92). In serial samples classified as (an)ovulatory by PDG, P4 Architect gave ROC AUC 0.95 (95% CI 0.89 to 1.01), with sensitivity and specificity for confirmation of ovulation of 0.90 and 0.91 at a cutoff of 1.67 μmol/mol. Automated P4 may potentially be as efficacious as PDG ELISA but research from a range of clinical settings is required

SHORTENING OF PRODUCT FLOW TIMES IN THE ENTERPRISE NIEROS METAL D.O.O.

Diplomska naloga zajema posnetek obstoječega stanja načrtovanja proizvodnje v podjetju NIEROS Metal d.o.o. Posnetek vsebuje analizo stanja v konstrukciji in analizo stanja v planski službi s posnetkom obstoječega stanja planiranja in upravljanja z materialom. Na osnovi posnetka obstoječih stanj in analize pretočnih časov so podani predlogi za skrajšanje pretočnih časov izdelkov. Rezultati analize nam kažejo na pojav ozkega grla v proizvodnem procesu, velike medfazne zaloge, subjektivne izdelovalne čase in slabo dinamiko upravljanja proizvodnje. V prihodnje bo potrebno delovati v smeri skrajševanj pretočnih časov z ukrepi, ki omogočajo skrajševanje prehodnih časov, nižanje medfaznih zalog in zmanjšanje nedovršene proizvodnje.The thesis begins with the analysis of the production planning process in company NIEROS Metal d.o.o. The analysis is divided into two parts. First one is the construction and design department analysis and the second part is an analysis of the planning department with reference to material management. Based on the analysis there are several proposals submitted how to reduce flow times in the production process. The results of the analysis indicate the occurrence of bottlenecks in the production process, large interfacial reserves, subjective production times and poor production process management. In future the company should work towards the reduction of flow times with measures that enable shortening of interfacial times and quicker completion of unfinished products

Designing jig for welding in robotic cell

Diplomsko delo prikazuje razvoj procesa varjenja v vpenjalni varilni pripravi. V uvodnih točkah je predstavljen splošen opis. V kasnejših poglavjih sledijo zahteve naročnika in podjetja Oprema Ravne d.o.o. Glavna tematika diplomskega dela se navezuje na področje varjena in konstruiranja varilne priprave. Bistveni del diplomskega dela je konstruiranje varilne priprave in izdelava tehnične dokumentacije potrebne za izvedbo iz virtualnega prostora v resničnost. S pomočjo virtualnega prostora lahko oblikujemo napravo, jo modificiramo in optimiziramo, da je cenejša, njena funkcija vpenjanja pa optimalna.The degree paper presents the development of the welding process in a fastening welding appliance. A general description is presented in the opening items. The commissions of the Oprema Ravne d.o.o company follow in the later chapters. The main theme of the degree paper is linked to the area of welding and the construction of a wielding appliance. It presents the fundamental technology of weldingthe essential part is the construction of a wielding appliance and the production of the technical documentation which is needed for the execution from the virtual space into reality. With the aid of the virtual space, we are able to create a device, modify it and of course optimise it, so that it is cheaper and it’s fastening function optimal