Decision support method for the selection of OMSs

With the increasing demand for highly complex, integrated and application-domain-specific systems engineering environments (SEEs) more or less specialized components of the SEEs are developed. An important component is the database management system (DBMS). As conventional DBMSs are not useful to fulfill the requirements on highly complex, persistent data structures, specialized DBMSs, namely object management systems (OMS), have been developed. An advantage of OMSs is that they further enhance the integration not only of data but also of processes. Currently several specialized OMSs with significantly different properties such as the data model, architecture and performance are available. As it is very difficult for an SEE developer to select the most appropriate OMS, we propose a decision support method which enables an SEE developer to identify his requirements and to compare the evaluation results of different OMSs. Additionally we present a practical experiment where we have applied the decision support method for comparing different OMSs. Experiences of the investigation are presented briefly

Inclusion of Electrochemically Active Guests by Novel Oxacalixarene Hosts

We demonstrate for the first time the utility of oxacalixarenes as hosts and investigate the forces that influence the thermodynamics of binding

Manipulating the Cavity of a Porous Material Changes the Photoreactivity of Included Guests

Changing an ether to a ketone within the framework of a bis-urea macrocycle has little effect on the supramolecular assembly of this building block into porous crystals but introduces a triplet sensitizer into the framework that dramatically alters the photochemical reactions of included guests

Origins of Selectivity for the [2+2] Cycloaddition of α,β-unsaturated Ketones within a Porous Self-assembled Organic Framework

This article studies the origins of selectivity for the [2+2] cycloadditions of α,β-unsaturated ketones within a porous crystalline host. The host, formed by the self-assembly of a bis-urea macrocycle, contains accessible channels of ∼6 Å diameter and forms stable inclusion complexes with a variety of cyclic and acyclic α,β-unsaturated ketone derivatives. Host 1 crystals provide a robust confined reaction environment for the highly selective [2+2] cycloaddition of 3-methyl-2-cyclopentenone, 2-cyclohexenone, and 2-methyl-2-cyclopentenone, forming their respective exo head-to-tail dimers in high conversion. The products are readily extracted from the self-assembled host and the crystalline host can be efficiently recovered and reused. Molecular modeling studies indicate that the origin of the observed selectivity is due to the excellent match between the size and shape of these guests to dimensions of the host channel and to the preorganization of neighboring enones into favorable reaction geometries. Small substrates, such as acrylic acid and methylvinylketone, were bound by the host and were protected from photoreactions. Larger substrates, such as 4,4-dimethyl-2-cyclohexenone and mesityl oxide, do not undergo selective [2+2] cycloaddition reactions. In an effort to understand these differences in reactivity, we examined these host−guest complexes by thermogravimetric analysis (TGA), NMR, powder X-ray diffraction (PXRD) and molecular modeling

Absorption Properties of a Porous Organic Crystalline Apohost Formed by a Self-Assembled Bis-Urea Macrocycle

We report herein the characterization and binding properties of a microporous crystalline host formed by the self assembly of a bis-urea macrocycle 1. Bis-urea macrocycle 1 has been designed to crystallize into stacked hollow columns. The self-assembly process is guided primarily by hydrogen bonding and aromatic stacking interactions that yield crystals of filled host 1âacetic acid (AcOH). The AcOH guests are bound in the cylindrical cavities of the crystal. The guest AcOH can be removed by heating to form a stable crystalline apohost 1. Apohost 1 displays a type I gas adsorption isotherm with CO2 that is consistent with an open framework microporous material. Apohost 1 binds a range of small molecule guests with specific stoichiometry. The formation of these inclusion complexes does not destroy the crystal framework and therefore apohost 1 can be reused, much like a zeolite. We investigated the structure of apohost 1 and its inclusion complexes by powder X-ray diffraction. The ability of guests to bind and their stoichiometry could be rationalized on the basis of the size, shape, and polarity of the guest molecules. Finally, the shape selectivity of these self-assembled porous materials was demonstrated in competition studies in which apohost 1 preferentially bound p-xylene from a mixture of xylene isomers

Guest Induced Transformations of Assembled Pyridyl Bis-Urea Macrocycles

Pyridine macrocycles with no cavities assembled into close packed columns yet absorbed guests including hydrogen, carbon dioxide, and iodine

Exercise training induces depot-specific adaptations to white and brown adipose tissue

Exercise affects whole-body metabolism through adaptations to various tissues, including adipose tissue (AT). Recent studies investigated exercise-induced adaptations to AT, focusing on inguinal white adipose tissue (WAT), perigonadal WAT, and interscapular brown adipose tissue (iBAT). Although these AT depots play important roles in metabolism, they account for only ∼50% of the AT mass in a mouse. Here, we investigated the effects of 3 weeks of exercise training on all 14 AT depots. Exercise induced depot-specific effects in genes involved in mitochondrial activity, glucose metabolism, and fatty acid uptake and oxidation in each adipose tissue (AT) depot. These data demonstrate that exercise training results in unique responses in each AT depot; identifying the depot-specific adaptations to AT in response to exercise is essential to determine how AT contributes to the overall beneficial effect of exercise11425439This work was supported by National Institutes of Health grants R01-HL138738 and K01-DK105109 (to K.I.S.), R01-DK099511 (to L.J.G.), and 5P30 DK36836 (Joslin Diabetes Center DRC). The authors thank Nathan Makarewicz for editorial contribution

Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study.

PURPOSE: This interim report of the GARNET phase I trial presents efficacy and safety of dostarlimab in patients with advanced or recurrent endometrial cancer (EC), with an analysis of tumor biomarkers as prognostic indicators. PATIENTS AND METHODS: A total of 153 patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and 161 patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) EC were enrolled and dosed. Patients received 500 mg dostarlimab every 3 weeks for 4 cycles, then 1000 mg every 6 weeks until progression. Primary endpoints were objective response rate (ORR) and duration of response (DOR). RESULTS: A total of 143 patients with dMMR/MSI-H EC and 156 patients with MMRp/MSS EC were evaluated for efficacy. ORR was 45.5% (n = 65) and 15.4% (n = 24) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. Median DOR for dMMR/MSI-H EC was not met (median follow-up, 27.6 months); median DOR for MMRp/MSS EC was 19.4 months. The ORRs by combined positive score (CPS) ≥1 status were 54.9% and 21.7% for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORRs by high tumor mutational burden (≥10 mutations/Mb) were 47.8% (43/90) and 45.5% (5/11) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORR in TP53mut or POLεmut molecular subgroups was 18.1% (17/94) and 40.0% (2/5), respectively. The safety profile of dostarlimab was consistent with previous reports. CONCLUSIONS: Dostarlimab demonstrated durable antitumor activity and safety in patients with dMMR/MSI-H EC. Biomarkers associated with EC may identify patients likely to respond to dostarlimab. TRIAL REGISTRATION: ClinicalTrials.gov NCT02715284