Characteristic Ring Research Articles

On the image of the trivial source ring in the ring of virtual characters of a finite group

We examine the cokernel of the canonical homomorphism from the trivial source ring of a finite group to the ring of $p$-rational complex characters. We use Boltje and Co\c{s}kun's theory of fibered biset functors to determine the structure of the cokernel. An essential tool in the determination of this structure is Bouc's theory of rational $p$-biset functors.

Multifaceted 3D-QSAR analysis for the identification of pharmacophoric features of biphenyl analogues as aromatase inhibitors

Aromatase, a cytochrome P450 enzyme, is responsible for the conversion of androgens to estrogens, which fuel the multiplication of cancerous cells. Inhibition of estrogen biosynthesis by aromatase inhibitors (AIs) is one of the highly advanced therapeutic approach available for the treatment of estrogen-positive breast cancer. Biphenyl moiety aids lipophilicity to the conjugated scaffold and enhances the accessibility of the ligand to the target. The present study is focused on the investigation of, the mode of binding of biphenyl with aromatase, prediction of ligand-target binding affinities, and pharmacophoric features essential for favorable for aromatase inhibition. A multifaceted 3D-QSAR (SOMFA, Field and Gaussian) along with molecular docking, molecular dynamic simulations and pharmacophore mapping were performed on a series of biphenyl bearing molecules (1–33) with a wide range of aromatase inhibitory activity (0.15–920 nM). Among the generated 3D-QSAR models, the Force field-based 3D-QSAR model (R 2 = 0.9151) was best as compared to SOMFA and Gaussian Field (R 2=0.7706, 0.9074, respectively). However, all the generated 3D-QSAR models were statistically fit, robust enough, and reliable to explain the variation in biological activity in relation to pharmacophoric features of dataset molecules. A four-point pharmacophoric features with three acceptor sites (A), one aromatic ring (R) features, AAAR_1, were obtained with the site and survival score values 0.890 and 4.613, respectively. The generated 3D-QSAR plots in the study insight into the structure–activity relationship of dataset molecules, which may help in the designing of potent biphenyl derivatives as newer inhibitors of aromatase. Communicated by Ramaswamy H. Sarma

Extraction and high-throughput sequencing of oak heartwood DNA: Assessing the feasibility of genome-wide DNA methylation profiling.

Tree ring features are affected by environmental factors and therefore are the basis for dendrochronological studies to reconstruct past environmental conditions. Oak wood often provides the data for these studies because of the durability of oak heartwood and hence the availability of samples spanning long time periods of the distant past. Wood formation is regulated in part by epigenetic mechanisms such as DNA methylation. Studies of the methylation state of DNA preserved in oak heartwood thus could identify epigenetic tree ring features informing on past environmental conditions. In this study, we aimed to establish protocols for the extraction of DNA, the high-throughput sequencing of whole-genome DNA libraries (WGS) and the profiling of DNA methylation by whole-genome bisulfite sequencing (WGBS) for oak (Quercus robur) heartwood drill cores taken from the trunks of living standing trees spanning the AD 1776-2014 time period. Heartwood contains little DNA, and large amounts of phenolic compounds known to hinder the preparation of high-throughput sequencing libraries. Whole-genome and DNA methylome library preparation and sequencing consistently failed for oak heartwood samples more than 100 and 50 years of age, respectively. DNA fragmentation increased with sample age and was exacerbated by the additional bisulfite treatment step during methylome library preparation. Relative coverage of the non-repetitive portion of the oak genome was sparse. These results suggest that quantitative methylome studies of oak hardwood will likely be limited to relatively recent samples and will require a high sequencing depth to achieve sufficient genome coverage.

Squaraine-Based Optical Sensors: Designer Toolbox for Exploring Ionic and Molecular Recognitions

Small molecule-based chromogenic and fluorogenic probes play an indispensable role in many sensing applications. Ideal optical chemosensors should provide selectivity and sensitivity towards a variety of analytes. Synthetic accessibility and attractive photophysical properties have made squaraine dyes an enticing platform for the development of chemosensors. This review highlights the versatility of modular assemblies of squaraine-based chemosensors and chemodosimeters that take advantage of the availability of various structurally and functionally diverse recognition motifs, as well as utilizing additional recognition capabilities due to the unique structural features of the squaraine ring.

Computational identification of 2,4-disubstituted amino-pyrimidines as L858R/T790M-EGFR double mutant inhibitors using pharmacophore mapping, molecular docking, binding free energy calculation, DFT study and molecular dynamic simulation.

The online version contains supplementary material available at 10.1007/s40203-021-00113-x.

Conformational control of bis-urea self-assembled supramolecular pH switchable low-molecular-weight hydrogelators

We report the synthesis and investigation into the structure-property relationships of eight different low molecular weight hydrogelators based on a bisaromatic urea core unit, all of which form gels as the pH of the solution is lowered. The low molecular weight hydrogelators are functionalized with carboxylic acid moieties on one aromatic ring, and the other aromatic ring features a nitro functional group either in the meta- or para-position relative to the urea linkage. Ortho-methyl substituents were installed on the aromatic rings to enforce a non-coplanar arrangement between the phenyl and urea moieties. Gel formation was triggered by the addition of a mineral acid or the ring-opening hydrolysis of glucono-δ-lactone. The low molecular weight hydrogelators were studied by a variety of analytical techniques, including NMR spectroscopy and rheology. In addition, their ability to uptake a dye, methylene blue, was determined by UV-vis spectroscopy.

S1767 COVID-19 Infection Masquerading as Inflammatory Bowel Disease

Introduction: Although COVID-19 infection has been associated with GI manifestations like nausea, vomiting, diarrhea, and even transaminitis, there is no known association between this virus and inflammatory bowel disease (IBD). Here we present the case of COVID-19 infection masquerading as IBD. We describe the instance of a COVID-19 patient with hematochezia, found to have histological changes similar to IBD on colon biopsy. Case Description/Methods: A 70 year-old female with PMH of HTN, DM, CAD, COPD, and recently diagnosed poorly differentiated colonic adenocarcinoma with signet ring features (status-post hemicolectomy and chemotherapy), presented to the ED with hypotension in the setting of nausea, vomiting, and diarrhea for 5 days. Patient had been started on chemotherapy two weeks prior and was found to have a blood pressure of 76/53, but was afebrile with no signs of tachycardia or hypoxia. Labs were significant for a white blood cell count of 0.67 (absolute neutrophil count 247), platelets of 115, lactate of 0.9, potassium of 6.2, BUN/creatinine of 88/5.6, and CRP of 20.78. COVID-19 PCR was positive. Abdominal CT identified non-specific ileitis, and GI was consulted due to concern for neutropenic enteritis and ileus. During the hospital stay, she developed hematochezia with a drop in hemoglobin. C. diff and GI PCR were negative. A colonoscopy was performed which showed patchy areas of edema, erythema, and ulceration (Figure 1B). Colon biopsies revealed crypt abscesses, consistent with IBD (Figure 1C). However, prior colonoscopy 4 months ago, which identified colon cancer, did not find any evidence of IBD (Figure 1A). Patient clinically declined, ultimately dying of acute hypoxic respiratory failure. Discussion: Given this patient’s age and the fact that she had previously had a colonoscopy that did not show evidence of crypt abscesses, it is unlikely she developed a new diagnosis of inflammatory bowel disease in the interim. It is more likely that the crypt abscesses noted on colon biopsy were due to COVID-19 infection. One study found that of 651 patients with COVID-19, 11.4% exhibited GI symptoms, most often developing acute gastritis or enteritis. We present this case to raise awareness of an unprecedented phenomenon in COVID-19 infection.Figure 1.: Figure 1a: Ulcerated mass in cecum as seen on initial colonoscopy. Figure 1b: Cecum on repeat colonoscopy one month later with marked improvement in ulcerations.

Superimposed electric/magnetic “dipole moment comparator” lattice design

In contrast to a “single particle table-top trap”, an essential feature of a storage ring “trap” is that 1010 or more particles can have their spins aligned in a polarized beam.This is a nunber of polarized particles large enough for the beam polarization to be detected externally,and fed back to permit external control of the beam polarization. Though the table large enoughfor any such “storage ring trap” is quite large, the level of achievable spin control, thoughclassical, not quantum mechanical, can be comparable to the control of one or a small number ofpolarized particles in a low energy trap.Motivated to investigate time reversal invariance, especially the detection of non-zero electricdipole moments (EDMs) thispaper describes the design of a low energy storage ring having the superimposed electric and magneticbending needed to “freeze” the spins of polarized beams. For electrons (of either sign) and protonsthe spins can be frozen with all-electric bending but, in general, superimposed electric/magnetic bending isrequired. Since constructive bending superposition in one direction implies destructive superposition inthe other direction, counter-circulating beams must differ, either in particle typeor momentum, in order for their orbits to be identical.For globally frozen spin operation the bunch polarizations remain constant relative to the momenta,for example remaining parallel to the circuating beam momentum vectors. With superimposed electric and magnetic bending,the globally frozen spin condition can be met over a continua (specific to particle type) of E/B ratios. When thiscondition is met, the out-of-plane, EDM-induced precession accumulates monitonically, which is obligatory forproducing a measurably large EDM signal. As Koop has explained, the EDM signal will still accumulate if thepolarization is allowed to “roll like a wheel” around a radial axis.

3D-QSAR-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies for Identification of Tubulin Inhibitors with Potential Anticancer Activity.

In this study, we aimed to develop a pharmacophore-based three-dimensional quantitative structure activity relationship (3D-QSAR) for a set including sixty-two cytotoxic quinolines (1-62) as anticancer agents with tubulin inhibitory activity. A total of 279 pharmacophore hypotheses were generated based on the survival score to build QSAR models. A six-point pharmacophore model (AAARRR.1061) was identified as the best model which consisted of three hydrogen bond acceptors (A) and three aromatic ring (R) features. The model showed a high correlation coefficient (R2 = 0.865), cross-validation coefficient (Q2 = 0.718), and F value (72.3). The best pharmacophore model was then validated by the Y-Randomization test and ROC-AUC analysis. The generated 3D contour maps were used to reveal the structure activity relationship of the compounds. The IBScreen database was screened against AAARRR.1061, and after calculating ADMET properties, 10 compounds were selected for further docking study. Molecular docking analysis showed that compound STOCK2S-23597 with the highest docking score (-10.948 kcal/mol) had hydrophobic interactions and can form four hydrogen bonds with active site residues.

Combined experimental and theoretical study on photoionization cross sections of benzonitrile and o/m/p-cyanotoluene

Photoionization cross sections (PICSs) for the products of the reaction from CN with toluene, including benzonitrile and o/m/p-cyanotoluene, were obtained at photon energies ranging from ionization thresholds to 14eV by tunable synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS). Theoretical calculations based on the frozen-core Hartree-Fock approximation and Franck-Condon simulations were carried out to cross-verify the measured PICS. The results show that the photoionization cross sections of benzonitrile and cyanotoluene isomers are similar. The generalized charge decomposition analysis was used to investigate the components of the highest occupied molecular orbital (HOMO) and HOMO-1. It was found that the HOMO and HOMO-1 of benzonitrile and cyanotoluene isomers are dominated by the features of the benzene ring, indicating that the substitution of CN and methyl has a minor influence on the PICS of the studied molecules. The reported PICS on benzonitrile and cyanotoluene isomers in the present work could contribute to the near-threshold PIMS experiments and determine the ionization and dissociation rates in interstellar space for these crucial species. The theoretical analysis on characteristics of molecular orbitals provides clues to estimating the PICS of similar substituted aromatic compounds.

Study on the influence of thin plasma thickness on electromagnetic wave attenuation

Plasma stealth technology has the advantage of real-time regulation of the absorbing band and does not affect the aerodynamic performance. The thin-layer cavity facilitates installation on special parts such as the surface of the aircraft body. However, the thickness of plasma directly determines the transmission distance of the radar wave in the plasma. When the thickness is decreased, the attenuation effect of the plasma on electromagnetic waves is reduced. In response to this problem, we studied the influence of thickness on electromagnetic wave scattering parameters, and established a fluid model of a planar transparent cavity ICP source using the multi-physics coupling method COMSOL in this paper. The accuracy of the fluid model is improved by adding the Boltzmann solver. COMSOL combined with ZT-FDTD method was used to establish the calculation model of ICP electromagnetic scattering parameter. The results of simulation show that the thickness has a significant influence on the ICP electromagnetic scattering parameters. When the thickness of plasma decreases, the central area of ne keeps deviating from the center of the cavity, the ring feature is enhanced, and the attenuation effect is generally in a downward trend. The main attenuation bandwidth in the frequency band also shows a shrinking trend. Through comparative experiments, the increase of pressure on the improvement of the main attenuation bandwidth compensates for the reduction of the main attenuation bandwidth caused by the decrease in thickness.

Relative depolarization of the black hole photon ring in GRMHD models of Sgr A* and M87*

ABSTRACT Using general relativistic magnetohydrodynamic simulations of accreting black holes, we show that a suitable subtraction of the linear polarization per pixel from total intensity images can enhance the photon ring feature. We find that the photon ring is typically a factor of ≃2 less polarized than the rest of the image. This is due to a combination of plasma and general relativistic effects, as well as magnetic turbulence. When there are no other persistently depolarized image features, adding the subtracted residuals over time results in a sharp image of the photon ring. We show that the method works well for sample, viable GRMHD models of Sgr A* and M87*, where measurements of the photon ring properties would provide new measurements of black hole mass and spin, and potentially allow for tests of the ‘no-hair’ theorem of general relativity.

ES17.04 Updates in Mesothelioma

The histologic subtype of malignant mesothelioma of the pleura has an impact on prognosis and treatment decisions and therefore has to be documented in diagnostic pathology reports. Epithelioid morphology is associated with a better prognosis when compared to sarcomatoid and biphasic subtypes. Surgical treatment may also have a prognostic impact in epithelioid subtype, while the same benefit is not seen in biphasic and sarcomatoid mesotheliomas. The 2020/21 WHO classification divides mesothelial proliferations into benign and preinvasive (adenomatoid tumor, well-differentiated papillary mesothelial tumor, mesothelioma in situ) and mesothelioma (localized pleural mesothelioma, diffuse pleural mesothelioma). The main change is the introduction of mesothelioma in situ (MIS) in the classification. Until recently the consensus was that MIS cannot be separated from reactive surface mesothelial proliferations on morphology alone. However, the concept of MIS was recently reintroduced for surface, usually flat or simple papillary, mesothelial proliferations with loss of BAP1 nuclear staining by immunohistochemistry or CDKN2A homozygous deletion, in the absence of radiologic or clinical gross evidence of the disease.1-3 Clinically, MIS is suspected in patients with unexplained recurrent effusions in the setting of heavy asbestos exposure, after irradiation and in patients with familial predisposition. The diagnosis requires sufficient tissue usually large biopsy samples. Small biopsy and cytology samples are not appropriate. Patients with MIS have a high incidence of eventual development of invasive mesothelioma. The updated classification of epithelioid mesotheliomas includes architectural patterns (tubular, papillary, tubulopapillary, trabecular, solid, adenomatoid and microcystic), stromal (myxoid) and cytologic (pleomorphic ,rhabdoid, deciduoid, small cell, clear cell, signet ring) features. Their identification is important for correct diagnosis, and some have prognostic values. Two cytologic features, transitional and pleomorphic, were previously classified as epithelioid patterns. They have shown a similar survival to biphasic and sarcomatoid mesothelioma and should be reclassified.5-8 Transitional features have appearance between epithelioid and sarcomatoid morphology, and have genomic characteristics similar to sarcomatoid subtype, and therefore were reclassified as cytologic feature of sarcomatoid mesothelioma. 6. Epithelioid mesotheliomas with transitional features should be reclassified as biphasic mesothelioma. Transitional features within biphasic mesothelioma carry negative prognostic significance, with a median survival of 6 months for cases with transitional features compared to 12 months for those without transitional features .6 Pleomorphic features, as described in epithelioid mesothelioma, can also be seen in sarcomatoid mesotheliomas. In contrast to transitional features, emerging genomic data suggest that a mesothelioma with pleomorphic features genomically can cluster with either sarcomatoid or epithelioid subtypes. Therefore, mesotheliomas with pleomorphic features should be classified based on the most predominant morphology as either sarcomatoid or epithelioid. A two-tier grading system for epithelioid mesothelioma allows the identification of more aggressive mesotheliomas and can be applied to biopsy and resection specimens 9, 10 It is primarily based on the combination of nuclear features, mitotic rate and the presence or absence of necrosis (Figure 1). Molecular testing in mesothelioma compared to other cancers is very limited. Recently, there have been several sequencing efforts to provide insights into the genomic characteristics and improved prognostic classification of mesothelioma. 10

Herboxidiene Features That Mediate Conformation-Dependent SF3B1 Interactions to Inhibit Splicing

Small molecules that target the spliceosome SF3B complex are potent inhibitors of cancer cell growth. The compounds affect an early stage of spliceosome assembly when U2 snRNP first engages the branch point sequence of an intron. Employing an inactive herboxidiene analog (iHB) as a competitor, we investigated factors that influence inhibitor interactions with SF3B to interfere with pre-mRNA splicing in vitro. Order-of-addition experiments show that inhibitor interactions are long lasting and affected by both temperature and the presence of ATP. Our data are also consistent with the model that not all SF3B conformations observed in structural studies are conducive to productive inhibitor interactions. Notably, SF3B inhibitors do not impact an ATP-dependent rearrangement in U2 snRNP that exposes the branch binding sequence for base pairing. We also report extended structure-activity relationship analysis of the splicing inhibitor herboxidiene. We identified features of the tetrahydropyran ring that mediate its interactions with SF3B and its ability to interfere with splicing. In the context of recent structures of SF3B bound to inhibitor, our results lead us to extend the model for early spliceosome assembly and inhibitor mechanism. We postulate that interactions between a carboxylic acid substituent of herboxidiene and positively charged SF3B1 side chains in the inhibitor binding channel are needed to maintain inhibitor occupancy while counteracting the SF3B transition to a closed state that is required for stable U2 snRNP interactions with the intron.

Construction and application of pharmacophore model of human carboxylesterase 2 inhibitors

According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.

Histological features of complete tracheal rings in congenital tracheal stenosis.

Congenital tracheal stenosis is a disease in which complete tracheal cartilage rings (CTCR) cause airway narrowing. Although tracheal cartilage malformation has been suggested as a cause of CTCR, no histological studies have been performed. Here, we report a comparison of the tissues from CTCR and normal tracheal cartilage. Thirty-one infants who underwent slide tracheoplasty at our institution from May 2016 to August 2019 were included. Tissues from ten autopsy cases without tracheal lesions were used as controls. The survey items were tracheal cartilage cell density, cartilage thickness, and chondrocyte findings. The median cartilage cell density from cases was 23/125 × 125µm2 and from controls was 23.5/125 × 125µm2 (p = 0.90). The median cartilage thickness from cases was 689µm and from controls was 840µm (p = 0.11). Comparing the ventral and dorsal sides of the CTCR tissues, the cell density was significantly different (median ventral 23/125 × 125 µm2; median dorsal 19.5/125 × 125µm2; p = 0.034). There were no significant findings in the chondrocytes of the CTCR tissues. CTCR tissues did not differ in cartilage density and thickness from normal tracheal cartilage.

Pharmacophore Based Virtual Screening for Identification of Novel CDK<sub>2</sub> Inhibitors

CDK2 is one of the most important members of Cyclin-dependent kinases. It is a critical modulator of various oncogenic signaling pathways, and its activity is vital for loss of proliferative control during oncogenesis. This work has focused on developing a pharmacophore model for CDK2 inhibitors by using a dataset of known inhibitors as a pre-filter throughout the virtual screening and docking process. Consequently, the best pharmacophore model was made of one hydrogen bond acceptor, and two aromatic ring features with a high correlation value of 0.906. The validation findings proved out that the selected model can be used as a filter to screen new molecules like Enamine kinase hinge region directed library against CDK2. As a result, 69 hits were subjected to molecular docking studies. Eventually, three compounds (5909, 701 and 8397) scored good interaction energy values and strong molecular interactions. Hence, they were identified as leads for novel CDK2 inhibitors as anticancer drugs.

Stereo Visual Odometry Based on Ring Feature Matching

Stereo Visual Odometry Based on Ring Feature Matching

High-contrast Hα imaging with Subaru/SCExAO + VAMPIRES

We present the current status of Hα high-contrast imaging observations with Subaru/Subaru Coronagraphic Extreme Adaptive Optics + VAMPIRES. Our adaptive optics correction at optical wavelengths in combination with (double) spectral differential imaging (SDI) and angular differential imaging (ADI) was capable of resolving a ring feature around omi Cet and detect the Hα counterpart of jet around RY Tau. We tested the post-processing by changing the order of ADI and SDI and both of the contrast limits achieved ∼10 − 3 to 5 × 10 − 4 at 0.3″, which is comparable to other Hα high-contrast imaging instruments in the Southern Hemisphere such as very large telescope (VLT)/spectro-polarimetric high-contrast exoplanet research, VLT/MUSE, and Magellan AO. Current wavefront sensing and adaptive optics correction at optical wavelengths empirically depend on airmass, and Subaru/VAMPIRES provide great opportunities for Hα high-contrast imaging for Northern Hemisphere targets.

Successful Management of Stress Urinary Incontinence in Women by a Contraceptive Device FemCap™ Pilot Study

Background: Women suffer silently from stress urinary incontinence (SUI). SUI is under-reported by women and under-diagnosed and treated by doctors. Treatment with pessaries is conservative and has significant limitations. These limitations include displacement, erosion, ulceration, and urethral obstruction. (SUI) is very prevalent among women of all ages, particularly menopausal women. The first line of SUI treatment is the ring pessary; however, more pessaries of different shapes and sizes have been introduced to achieve better results. Objectives: To provide women with a safer, more effective device to treat SUI. Materials and Methods: The FemCap combines the ring and space-occupying pessary features into one device, making it much more successful. The bowl of the dome of the FemCap covers the cervix and prevents it from prolapsing. The rim fits snugly into the vaginal fornices that support the bladder neck. The brim flares outward, pushing against the cystocele and the urethrocele anteriorly to restore the urethra and the bladder’s anatomy. Forty-one women who had had significant SUI were recruited and asked to compare their experience for one week before using the FemCap and two weeks later. The FemCap was self-inserted and removed by the participants. Results: Thirty-four women out of 41 were completely dry after two weeks of using the FemCap, while four women were partially dry, and three women did not notice any change. The participants reported no side effects, and pelvic examinations did not show any erosion or ulceration of the vagina. Conclusion: The FemCap is safe and effective in restoring the bladder and urethra’s anatomy, which could make it ideal for the treatment and prevention of mild to moderate SUI. More studies are warranted to prove the utility of the FemCap further to manage SUI.