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We investigate here the ability of N-iodophthalimide (NIPht) to act as a halogen bond (HaB) donor, in comparison with well-known HaB donors N-iodosuccinimide (NISucc) and N-iodosaccharin (NISacc). The structure of NIPht itself is reported, together with those of neutral adducts with 4-dimethylaminopyridine (DMAP), 4,4′-bipyridine and 2,2′-bipyridine derivatives. Comparison with analogous adducts involving NISucc and NISacc shows that NIPht behaves essentially like NISucc as a HaB donor, both forming weaker adducts than NISacc with a given Lewis base. A symmetric anionic complex [NPht–I–NPht]− is isolated in the presence of [K(18-crown-6)]+. It exhibits N–I distances very close to those observed in the known [NSucc–I–NSucc]− and [NSacc–I–NSacc]− species (2.24–2.26 Å), confirming the 3-center–4-electron (3c–4e) character of the bonding in these species. This similarity confirms the peculiar character of the only other reported salt of [NPht–I–NPht]−, namely [Me4N][NPht–I–NPht], where the longer N–I distances (2.29 Å) are a consequence of a specific solid-state arrangement and C–H⋯O hydrogen bonds. [ABSTRACT FROM AUTHOR]

Abstract: Without employing high dilution conditions, the fourfold 2+2 Perkin reaction of 1,6-pyrenylene-diglyoxylic acid with its reduction product 1,6-pyrenylene-diacetic acid yields the corresponding tetrameric conjugated macrocycle in 25% overall yield [...]

Author(s): Gabriela Popescu (corresponding author) [1]; Antoine Robert [2]; James R. Howe [2]; Anthony Auerbach [1] At central excitatory synapses, N -methyl-;d; -aspartate (NMDA) receptors, which have a high affinity [...]

Simple Summary: Surgical resection of perihilar cholangiocarcinoma (PHC), a rare malignant bile duct tumor arising in the hepatic hilum, requires either right- or left-sided liver resections depending on tumor-side predominance. Margin-free resection remains the only curative-intent treatment and extended liver resections (trisectionectomies) are needed for advanced (Bismuth type IV) PHC. However, the clinical outcomes of left (LTS) and right trisectionectomies (RTS) have so far not been compared for the resection of advanced PHC. In this retrospective study of consecutive cases of Bismuth type IV PHC, RTS (42 patients) and LTS (25 patients) were compared in terms of postoperative morbidity and patient survival. Although LTS was more frequently associated with arterial reconstructions, the postoperative liver failure rate was lower and overall survival was better as compared to RTS. How the side of an extended liver resection impacts the postoperative prognosis of advanced perihilar cholangiocarcinoma (PHC) is still controversial. We compared the outcomes of right (RTS) and left trisectionectomies (LTS) in Bismuth-Corlette (BC) type IV PHC resection. All patients undergoing RTS or LTS for BC type IV PHC in a single tertiary center between January 2012 and December 2019 were compared retrospectively. The endpoints were perioperative outcomes, long-term overall (OS), and disease-free survival (DFS). Among 67 hepatic resections for BC type IV PHC, 25 (37.3%) were LTS and 42 (63.7%) were RTS. Portal vein and artery resection rates were 40% and 52.4% (p = 0.29), and 24% and 0% (p < 0.001) in the LTS and RTS groups, respectively. The severe complication (Clavien–Dindo > IIIa) rate was comparable (36% vs. 21.5%, p = 0.357) while the postoperative liver failure (POLF) rate was lower in the LTS group (16% vs. 38%, p = 0.048). The R0 resection rate was similar between groups (81% vs. 92%; p = 0.154). The five-year OS rate was higher in the LTS group (66% vs. 30%, p = 0.009) while DFS was comparable (43% vs. 18%, p = 0.11). Based on multivariable analysis, the side of the trisectionectomy was an independent predictor of OS. Compared with RTS, LTS is associated with lower POLF and higher overall survival despite more frequent arterial reconstructions in type IV PHC. Although technically more demanding, LTS may be preferred in the treatment of advanced PHC. [ABSTRACT FROM AUTHOR]

Abstract Background The jellyfish green fluorescent protein (GFP) can be inserted into the middle of another protein to produce a functional, fluorescent fusion protein. Finding permissive sites for insertion, however, can be difficult. Here we describe a transposon-based approach for rapidly creating libraries of GFP fusion proteins. Results We tested our approach on the glutamate receptor subunit, GluR1, and the G protein subunit, αs. All of the in-frame GFP insertions produced a fluorescent protein, consistent with the idea that GFP will fold and form a fluorophore when inserted into virtually any domain of another protein. Some of the proteins retained their signaling function, and the random nature of the transposition process revealed permissive sites for insertion that would not have been predicted on the basis of structural or functional models of how that protein works. Conclusion This technique should greatly speed the discovery of functional fusion proteins, genetically encodable sensors, and optimized fluorescence resonance energy transfer pairs.

Cyclobis[n]helicenes (n=3 or 5) are chiral D2‐symmetric π‐conjugated macrocycles with stable lemniscular, or figure‐eight, shapes. The conformational analysis of five different cyclobis[n]helicenes revealed that these molecules can only exist as their lemniscular conformers with high barriers to enantiomerization (>200 kJ mol−1). The enantiomers of a cyclobis[5]helicene were resolved by HPLC and their unusual chiroptical properties were attributed to the inherent chirality of their macrocyclic figure‐eight. [ABSTRACT FROM AUTHOR]

Saddle- and propeller-shaped macrocycles are obtained by fourfold Perkin condensations in transient high dilution of 4,4′-bis(phenylglyoxylic acid) with either 4,4′-bis(phenylacetic acid) or p-phenylenediacetic acid, followed by four-fold oxidative photocyclizations. In the saddle-shaped tetraphenanthrylene, the angle between opposite phenanthrene planes is close to the value of 90° of an ideal saddle. In the two helicene fragments of the propeller-shaped double [5]helicene, the geometry of unsubstituted [5]helicene is preserved without major macrocycle-induced distortions. [ABSTRACT FROM AUTHOR]

Without employing high dilution conditions, the fourfold 2+2 Perkin reaction of 1,6-pyrenylene-diglyoxylic acid with its reduction product 1,6-pyrenylene-diacetic acid yields the corresponding tetrameric conjugated macrocycle in 25% overall yield after in-situ esterification. The macrocycle adopts a square fourfold symmetry in the crystal, with near-vertical pyrene walls that alternatingly tilt upwards and downwards. [ABSTRACT FROM AUTHOR]

Glutamate binds to AMPA receptors within a deep cleft between two globular protein domains (domains 1 and 2). Once glutamate binds, the cleft closes, and agonist-bound structures of the isolated ligand binding core suggest that closure of the binding cleft is sufficiently complete that it essentially prevents ligand dissociation. There is also considerable evidence supporting the view that cleft closure is the initial conformational change that triggers receptor activation and desensitization, and it has been dearly demonstrated that there is a correlation between the degree of cleft closure and agonist efficacy. It is unknown, however, whether the stability of binding deft closure also influences receptor-channel properties. The crystallographic structures indicate that closed-cleft conformations are stabilized by the formation of hydrogen bonds that involve amino acid side chains of residues in domains 1 and 2. We show here that mutations that disrupt one such cross-deft hydrogen bond (in the AMPA receptor subunit GluR2) decrease both agonist affinity and efficacy. The same mutations also hasten recovery from desensitization. We conclude that the stability of binding cleft closure has a significant impact on AMPA receptor function and is a major determinant of the apparent affinity of agonists. The results suggest that the stability of cleft closure has been tuned so that glutamate dissociates as rapidly as possible yet remains a full agonist. [ABSTRACT FROM AUTHOR]

Deals with a study which demonstrated the dependence of AMPA-type glutamate receptor desensitization on the number of subunits occupied by glutamate. Materials and methods; Results; Discussion.

Glutamate-gated ion channels are widely expressed in neurons where they serve a host of cellular functions. An appealing, but yet unexplored, way to delineate the functions of particular glutamate receptor subtypes is to direct the expression of dominant-negative and gain-of-function mutant subunits. We tested the ability of two dominant-negative subunits, an α-amino-3-hydroxy-5-methyl-isoxazolproprionic acid receptor subunit and a kainate receptor subunit, to silence recombinant and neuronal glutamate receptors. Co-expression studies in non-neuronal cells indicated that the inclusion of a single mutant subunit was sufficient to silence the receptor. When expressed in cerebellar granule cells, the dominant-negative subunits silenced native channels in a subtype-specific fashion. Immunocytochemical staining of control and transfected neurons, as well as studies with a gain-of-function glutamate receptor-1 mutant, indicated that the mutant subunits were expressed at levels roughly equal to the total abundance of related native subunits, and both dominant-negatives suppressed native channel expression 60–65% when tested 24 h post-transfection. If co-assembly of the mutant subunits with related native subunits is combinatorial, this level of suppression gives receptor half-lives of approximately 20 h. [Copyright &y& Elsevier]

Background: The jellyfish green fluorescent protein (GFP) can be inserted into the middle of another protein to produce a functional, fluorescent fusion protein. Finding permissive sites for insertion, however, can be difficult. Here we describe a transposon-based approach for rapidly creating libraries of GFP fusion proteins. Results: We tested our approach on the glutamate receptor subunit, GluR1, and the G protein subunit, αs. All of the in-frame GFP insertions produced a fluorescent protein, consistent with the idea that GFP will fold and form a fluorophore when inserted into virtually any domain of another protein. Some of the proteins retained their signaling function, and the random nature of the transposition process revealed permissive sites for insertion that would not have been predicted on the basis of structural or functional models of how that protein works. Conclusion: This technique should greatly speed the discovery of functional fusion proteins, genetically encodable sensors, and optimized fluorescence resonance energy transfer pairs. [ABSTRACT FROM AUTHOR]

Investigates the role of N-methyl-D-aspartate receptors in O-2A glial precursor cells in regulating polysialic acid-neural cell adhesion molecule expression and cell migration. Myelin formation; Interactions between ionotropic receptors, intracellular signaling and cell adhesion molecule; Cell surface properties.

Objectives: To assess the image quality of ultra-high-resolution (UHR) virtual monoenergetic images (VMIs) at 40 keV compared to 70 keV, using spectral photon-counting CT (SPCCT) and dual-layer dual-energy CT (DECT) for coronary computed tomography angiography (CCTA)., Methods and Materials: In this prospective IRB-approved study, 26 high-risk patients were included. CCTA was performed both with an SPCCT in UHR mode and with one of two DECT scanners (iQOn or CT7500) within 3 days. 40 keV and 70 keV VMIs were reconstructed for both modalities. Stenoses, blooming artefacts, and image quality were compared between all four reconstructions., Results: Twenty-six patients (4 women [15%]) and 28 coronary stenoses (mean stenosis of 56% ± 16%) were included. 40 keV SPCCT gave an overall higher quality score (5 [5, 5]) than 70 keV SPCCT (5 [4, 5], 40 keV DECT (4 [3, 4]) and 70 keV SPCCT (4 [4, 5]), p < 0.001). Less variability in stenosis measurement was found with SPCCT between 40 keV and 70 keV (bias: -1% ± 3%, LoA: 6%) compared with DECT (-6% ± 8%, LoA 16%). 40 keV SPCCT vs 40 keV DECT showed a -3% ± 6% bias, whereas 40 keV SPCCT vs 70 keV DECT showed a -8% ± 6% bias. From 70 keV to 40 keV, blooming artefacts did not increase with SPCCT (mean +2% ± 5%, p = 0.136) whereas they increased with DECT (mean +7% ± 6%, p = 0.005)., Conclusion: UHR 40 keV SPCCT VMIs outperformed 40 keV and 70 keV DECT VMIs for assessing coronary artery stenoses, with no impairment compared to 70 keV SPCCT VMIs., Key Points: Question Use of low virtual mono-energetic images at 40 keV using spectral dual-energy and photon-counting CT systems is not yet established for diagnosing coronary artery stenosis. Findings UHR 40 keV SPCCT enhances diagnostic accuracy in coronary artery assessment. Clinical relevance By combining spectral sensitivity with lower virtual mono-energetic imaging and ultra-high spatial resolution, SPCCT enhances coronary artery assessment, potentially leading to more accurate diagnoses and better patient outcomes in cardiovascular imaging., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Salim A. Si-Mohamed. Conflict of interest: Marjorie Villien and Hugo Lacombe are employed by the manufacturer of the SPCCT system used in this report. No other conflict of interest is to be reported. Statistics and biometry: One of the authors has significant statistical expertise. Informed consent: Written informed consent was obtained from all subjects (patients) in this study. Ethical approval: Our local institutional review board (IRB) approved the study (Hospices Civils de Lyon, approval number: 2019-A02945–52). Study subjects or cohorts overlap: Study subjects have been previously reported. Methodology: Prospective Diagnostic Performed at one institution, (© 2024. The Author(s).)

Purpose: The purpose of this study was to compare lung image quality obtained with ultra-high resolution (UHR) spectral photon-counting CT (SPCCT) with that of dual-layer CT (DLCT), at standard and low dose levels using an image quality phantom and an anthropomorphic lung phantom., Methods: An image quality phantom was scanned using a clinical SPCCT prototype and an 8 cm collimation DLCT from the same manufacturer at 10 mGy. Additional acquisitions at 6 mGy were performed with SPCCT only. Images were reconstructed with dedicated high-frequency reconstruction kernels, slice thickness between 0.58 and 0.67 mm, and matrix between 512 2 and 1024 2 mm, using a hybrid iterative algorithm at level 6. Noise power spectrum (NPS), task-based transfer function (TTF) for iodine and air inserts, and detectability index (d') were assessed for ground-glass and solid nodules of 2 mm to simulate highly detailed lung lesions. Subjective analysis of an anthropomorphic lung phantom was performed by two radiologists using a five-point quality score., Results: At 10 mGy, noise magnitude was reduced by 29.1 % with SPCCT images compared to DLCT images for all parameters (27.1 ± 11.0 [standard deviation (SD)] HU vs. 38.2 ± 1.0 [SD] HU, respectively). At 6 mGy with SPCCT images, noise magnitude was reduced by 8.9 % compared to DLCT images at 10 mGy (34.8 ± 14.1 [SD] HU vs. 38.2 ± 1.0 [SD] HU, respectively). At 10 mGy and 6 mGy, average NPS spatial frequency (f av ) was greater for SPCCT images (0.75 ± 0.17 [SD] mm -1 ) compared to DLCT images at 10 mGy (0.55 ± 0.04 [SD] mm -1 ) while remaining constant from 10 to 6 mGy. At 10 mGy, TTF at 50 % (f 50 ) was greater for SPCCT images (0.92 ± 0.08 [SD] mm -1 ) compared to DLCT images (0.67 ± 0.06 [SD] mm -1 ) for both inserts. At 6 mGy, f 50 decreased by 1.1 % for SPCCT images, while remaining greater compared to DLCT images at 10 mGy (0.91 ± 0.06 [SD] mm -1 vs. 0.67 ± 0.06 [SD] mm -1 , respectively). At both dose levels, d' were greater for SPCCT images compared to DLCT for all clinical tasks. Subjective analysis performed by two radiologists revealed a greater median image quality for SPCCT (5; Q1, 4; Q3, 5) compared to DLCT images (3; Q1, 3; Q3, 3)., Conclusion: UHR SPCCT outperforms DLCT in terms of image quality for lung imaging. In addition, UHR SPCCT contributes to a 40 % reduction in radiation dose compared to DLCT., Competing Interests: Declaration of competing interest Hugo Lacombe and Marjorie Villien are employees of Philips Healthcare. The other authors have no relevant conflicts of interest or industry support for the project to declare., (Copyright © 2024. Published by Elsevier Masson SAS.)

In recent years, computed tomography (CT) has undergone a number of developments to improve radiological care. The most recent major innovation has been the development of photon-counting detectors. By comparison with the energy-integrating detectors traditionally used in CT, these detectors offer better dose efficiency, eliminate electronic noise, improve spatial resolution and have intrinsic spectral sensitivity. These detectors also allow the energy of each photon to be counted, thus improving the sampling of the X-ray spectrum in multiple energy bins, to better distinguish between photoelectric and Compton attenuation coefficients, resulting in better spectral images and specific color K-edge images. The purpose of this article was to make the reader more familiar with the basic principles and techniques of new photon-counting CT systems equipped with photon-counting detectors and also to describe the currently available devices that could be used in clinical practice., Competing Interests: Declaration of competing interest The authors have no relevant conflict of interest to disclose in relation with this article., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Ultrathin gold nanowires (NWs) dispersed in hexane were prepared by chemical reduction of HAuCl4 in oleylamine, along with nanospheres (NSs), side products of the reaction. X-ray photoelectron spectroscopy and small-angle X-ray scattering evidenced a stabilization of these nano-objects by oleylammonium chloride surfactants. The directed assembly of these nano-objects on surfaces was performed by atomic force microscopy (AFM) nanoxerography in a few seconds. Selective assembly of gold NWs only occurred on positively charged patterns, while NSs assembled more specifically on the negatively charged ones. This sorting suggests that the strong electric field generated by the charge patterns induced a negative effective charge on the gold NWs and a weak positive effective charge on the NSs. Such difference could be explained by the ion organization at the colloid surface, monolayered in the case of NWs, and bilayered in the case of NSs. By adjusting the design of the positive patterns and the experimental conditions of development, single gold nanowires were successfully assembled by AFM nanoxerography on predefined sites of surfaces without damaging them, opening the way for future electrical and mechanical characterizations.

Background: Developments in an artificial pancreas (AP) for patients with type 1 diabetes have allowed a move toward performing outpatient clinical trials. "Home-like" environment implies specific protocol and system adaptations among which the introduction of remote monitoring is meaningful. We present a novel tool allowing multiple patients to monitor AP use in home-like settings., Methods: We investigated existing systems, performed interviews of experienced clinical teams, listed required features, and drew several mockups of the user interface. The resulting application was tested on the bench before it was used in three outpatient studies representing 3480 h of remote monitoring., Results: Our tool, called DiAs Web Monitoring (DWM), is a web-based application that ensures reception, storage, and display of data sent by AP systems. Continuous glucose monitoring (CGM) and insulin delivery data are presented in a colored chart to facilitate reading and interpretation. Several subjects can be monitored simultaneously on the same screen, and alerts are triggered to help detect events such as hypoglycemia or CGM failures. In the third trial, DWM received approximately 460 data per subject per hour: 77% for log messages, 5% for CGM data. More than 97% of transmissions were achieved in less than 5 min., Conclusions: Transition from a hospital setting to home-like conditions requires specific AP supervision to which remote monitoring systems can contribute valuably. DiAs Web Monitoring worked properly when tested in our outpatient studies. It could facilitate subject monitoring and even accelerate medical and technical assessment of the AP. It should now be adapted for long-term studies with an enhanced notification feature., (© 2013 Diabetes Technology Society.)

AMPA-type glutamate receptors are tetrameric ion channels that mediate fast excitatory synaptic transmission in the mammalian brain. When agonists occupy the binding domain of individual receptor subunits, this domain closes, triggering rearrangements that couple agonist binding to channel opening. Here we compare the kinetic behavior of GluR2 channels activated by four different ligands, glutamate, AMPA, quisqualate, and 2-Me-Tet-AMPA, full agonists that vary in potency by up to two orders of magnitude. After reduction of desensitization with cyclothiazide, deactivation decays were strongly agonist dependent. The time constants of decay increased with potency, and slow components in the multiexponential decays became more prominent. The desensitization decays of agonist-activated currents also contained multiple exponential components, but they were similar for the four agonists. The time course of recovery from desensitization produced by each agonist was described by two sigmoid components, and the speed of recovery varied substantially. Recovery was fastest for glutamate and slowest for 2-Me-Tet-AMPA, and the amplitude of the slow component of recovery increased with agonist potency. The multiple kinetic components appear to arise from closed-state transitions that precede channel gating. Stargazin increases the slow kinetic components, and they likely contribute to the biexponential decay of excitatory postsynaptic currents.