Orientational Susceptibility and Elastic Constants Near the Nematic-Isotropic Phase Transition for Trimers with Terminal-Lateral-Lateral-Terminal Connections

Magnetically induced Freedericksz measurements were performed in the nematic liquid crystal phase to extract the elastic constants of a terminal-lateral-lateral-terminal trimer, i.e., a trimer in which the connections to the first and third mesogens are at the end of the mesogen and both attachments to the central mesogen are lateral. Polymeric liquid crystals based on this unit have negative Poisson ratios. Additionally, electric field Kerr measurements were performed in the isotropic phase to extract the orientational susceptibility. The elastic constants were found to be similar to values obtained for typical monomers, albeit with a slightly enhanced ratio K-33/K-11 and reduced ratio K-11/K-22 especially near the transition temperature. The temperature dependence of the susceptibility was found to deviate significantly from that of typical monomers. The observed behavior is discussed in terms of coupled order parameters representing the terminal and core mesogens of the molecule

Pretransitional Behavior Above the Nematic-Isotropic Phase Transition of an Auxetic Trimer Liquid Crystal

Static Light scattering and electric field-induced Kerr measurements were performed above the nematic-isotropic phase transition of a terminal-lateral-lateral-terminal negative Poisson ratio trimer. Far both measurements the inverse susceptibility was observed to be nearly linear with temperature, a result inconsistent with our previously reported Kerr data [Phys. Rev. E 58, 2041 (1998)]. [S1063-651X(99)11010-9]

Exploring Mars at the nanoscale: applications of transmission electron microscopy and atom probe tomography in planetary exploration

The upcoming Mars Sample Return (MSR) mission aims to deliver small quantities of Martian rocks to the Earth. Investigating these precious samples requires the development and application of techniques that can extract the greatest amount of high quality data from the minimum sample volume, thereby maximising science return from MSR. Atom probe tomography (APT) and transmission electron microscopy (TEM) are two complementary techniques that can obtain nanoscale structural, geochemical and, in the case of atom probe, isotopic information from small sample volumes. Here we describe how both techniques operate, as well as review recent developments in sample preparation protocols. We also outline how APT has been successfully applied to extraterrestrial materials in the recent past. Finally, we describe how we have studied Martian meteorites using TEM and APT in close coordination in order to characterise the products of water/rock interactions in t h e cru st of Ma r s – a k ey sc ie n ce goal of MSR. Our results provide new insights into the Martian hydrosphere and the mechanisms of anhydrous-hydrous mineral replacement. In light of the unique results provided by these tools, APT and TEM should form a crucial part at the culmination of a correlative analytical pipeline for MSR mission materials

PPARgamma in complex with an antagonist and inverse agonist: a tumble and trap mechanism of the activation helix

Peroxisome proliferator activated receptor γ (PPARγ) is a nuclear receptor and target for antidiabetics that increase insulin sensitivity. Owing to the side effects of PPARγ full agonists, research has recently focused on non-activating ligands of PPARγ, which increase insulin sensitivity with decreased side effects. Here, we present the crystal structures of inverse agonist SR10171 and a chemically related antagonist SR11023 bound to the PPARγ ligand-binding domain, revealing an allosteric switch in the activation helix, helix 12 (H12), forming an antagonist conformation in the receptor. H12 interacts with the antagonists to become fixed in an alternative location. Native mass spectrometry indicates that this prevents contacts with coactivator peptides and allows binding of corepressor peptides. Antagonists of related nuclear receptors act to sterically prevent the active configuration of H12, whereas these antagonists of PPARγ alternatively trap H12 in an inactive configuration, which we have termed the tumble and trap mechanism.Rebecca L. Frkic, Andrew C. Marshall, Anne-Laure Blayo, Tara L. Pukala, Theodore M. Kamenecka, Patrick R. Griffin, and John B. Brunin

Iterative fitting of magic-angle-spinning NMR spectra

Bio-organic Synthesi

Patient free text reporting of symptomatic adverse events in cancer clinical research using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Objective: The study sought to describe patient-entered supplemental information on symptomatic adverse events (AEs) in cancer clinical research reported via a National Cancer Institute software system and examine the feasibility of mapping these entries to established terminologies. Materials and Methods: Patients in 3 multicenter trials electronically completed surveys during cancer treatment. Each survey included a prespecified subset of items from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Upon completion of the survey items, patients could add supplemental symptomatic AE information in a free text box. As patients typed into the box, structured dropdown terms could be selected from the PRO-CTCAE item library or Medical Dictionary for Regulatory Activities (MedDRA), or patients could type unstructured free text for submission. Results: Data were pooled from 1760 participants (48% women; 78% White) who completed 8892 surveys, of which 2387 (26.8%) included supplemental symptomatic AE information. Overall, 1024 (58%) patients entered supplemental information at least once, with an average of 2.3 per patient per study. This encompassed 1474 of 8892 (16.6%) dropdowns and 913 of 8892 (10.3%) unstructured free text entries. One-third of the unstructured free text entries (32%) could be mapped post hoc to a PRO-CTCAE term and 68% to a MedDRA term. Discussion: Participants frequently added supplemental information beyond study-specific survey items. Almost half selected a structured dropdown term, although many opted to submit unstructured free text entries. Most free text entries could be mapped post hoc to PRO-CTCAE or MedDRA terms, suggesting opportunities to enhance the system to perform real-time mapping for AE reporting. Conclusions: Patient reporting of symptomatic AEs using a text box functionality with mapping to existing terminologies is both feasible and informative