Quinoline-based small molecules have been explored and being developed as anti-inflammatory agents targeting several pharmacological targets namely Phosphodiesterase 4 (PDE4), Transient Receptor ...Potential Vanilloid 1 (TRPV1), TNF-α converting enzyme (TACE) and Cyclooxygenase (COX). Efforts on Structure Activity Relationship (SAR) studies revealed that the pharmacological activities and target specificities of these quinoline derivatives were mainly dependent on the nature and position of substituent(s) present on the quinoline ring. For example, quinolines having carboxamide moiety displayed TRPV1 antagonism whereas that with carboxylic acid showed COX-inhibition. Similarly, quinolines possessing aniline moiety at C-4, aryl group at C-8 and oxazole ring at C-5 showed PDE4 inhibition. These quinoline derivatives were synthesized by using various synthetic approaches like Pd-mediated C-C (e.g. Suzuki, Sonogashira type coupling etc.) or C-N (the Buchwald-Hartwig type coupling) or C-S bond formation, AlCl₃ induced C-C bond formation, traditional amide bond formation or amination, formation of ether linkage or additional heterocyclic rings. All these efforts resulted in the discovery of several quinoline-based anti-inflammatory agents for the potential treatment of acute as well as chronic inflammatory diseases.
Cystic fibrosis associated liver disease (CFLD) is the third largest cause of mortality in CF. Our aim was to define the burden of CFLD in the UK using national registry data and identify risk ...factors for progressive disease.
A longitudinal population-based cohort study was conducted. Cases were defined as all patients with CFLD identified from the UK CF Registry, 2008-2013 (n = 3417). Denominator data were derived from the entire UK CF Registry. The burden of CFLD was characterised. Regression analysis was undertaken to identify risk factors for cirrhosis and progression.
Prevalence of CFLD increased from 203.4 to 228.3 per 1000 patients during 2008-2013. Mortality in CF patients with CFLD was more than double those without; cirrhotic patients had higher all-cause mortality (HR 1.54, 95% CI 1.09 to 2.18, p = 0.015). Median recorded age of cirrhosis diagnosis was 19 (range 5-53) years. Male sex, Pseudomonas airway infection and CF related diabetes were independent risk factors for cirrhosis. Ursodeoxycholic acid use was associated with prolonged survival in patients without cirrhosis.
This study highlights an important changing disease burden of CFLD. The prevalence is slowly increasing and, importantly, the disease is not just being diagnosed in childhood. Although the role of ursodeoxycholic acid remains controversial, this study identified a positive association with survival.
Particle physicists and cosmologists have sought axion-like particles (ALPs) ever since they were postulated in quantum chromodynamics and string theory. We propose probing the electromagnetic ...interaction between ALPs and photons using the inter-conversion of cosmic microwave background (CMB) photons and ALPS in the magnetic field of galaxy clusters. Importantly, the unique, polarized non-gravitational signature of ALPs we propose can be measured from high resolution CMB imaging experiments even if ALPs are not the dark matter; our approach is therefore directly competitive with laboratory experiments. The search for this signal from the large sample of galaxy clusters from the upcoming CMB missions can provide orders of magnitude better constraints on the coupling between photons and ALPs than the current bounds available from any experiments. The ALP mass range and couplings that will be probed by the CMB experiments are unexplored to date and complementary with other cosmological searches from the imprints of ALPs on the cosmic density field.
Summary Background Fetal alcohol spectrum disorder (FASD) is related to many comorbidities because of the permanent effects of prenatal alcohol exposure on the fetus. We aimed to identify the ...comorbid conditions that co-occur in individuals with FASD and estimate the pooled prevalence of comorbid conditions occurring in individuals with fetal alcohol syndrome (FAS). Methods We did a systematic literature search of studies reporting on the comorbidity and cause of death in individuals with FASD using multiple electronic bibliographic databases, searching for studies published up to July, 2012. We included original research published in a peer-reviewed journal in the English language. We used the following criteria for determining study quality: use of an established FASD diagnostic guideline, study setting, method of data collection, and sample size. All comorbid disease conditions were coded according to the International Classification of Diseases, tenth revision (ICD-10). To estimate the pooled prevalence of comorbid conditions found to co-occur in individuals with FAS, we did meta-analyses assuming a random-effects model. Findings Of 5068 studies found, 127 met eligibility criteria for data extraction. From those studies, we identified 428 comorbid conditions co-occurring in individuals with FASD, spanning across 18 of 22 chapters of the ICD-10. The most prevalent disease conditions were within the sections of congenital malformations, deformities, and chromosomal abnormalities, and mental and behavioural disorders. 33 studies reported data for frequency in a total of 1728 participants with FAS. The five comorbid conditions with the highest pooled prevalence (between 50% and 91%) included abnormal results of function studies of peripheral nervous system and special senses, conduct disorder, receptive language disorder, chronic serous otitis media, and expressive language disorder. Interpretation The high prevalence of comorbid conditions in individuals with FASD highlights the importance of assessing prenatal alcohol exposure as a substantial clinical risk factor for comorbidity. The harmful effects of alcohol on a developing fetus represent many cases of preventable disability, and thus, alcohol use during pregnancy should be recognised as a public health problem globally. Funding Public Health Agency of Canada.
Although the role of metastatic cancer stem cells (mCSCs) in tumor progression has been well documented, our study reveals a hitherto unidentified role of tumorigenic intrinsic CSCs (iCSCs) in breast ...cancer metastasis. We show that unlike highly migratory mCSCs residing in the breast tumor disseminating/peripheral regions, iCSCs populate the inner mass of the tumor and are non-migratory. However iCSCs, via paracrine signaling, induce conversion of non-stem cancer cells to CSCs that (i) are identical to the previously reported mCSCs, and (ii) in contrast to iCSCs, express chemokine receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), which is crucial for their metastatic potential. These mCSCs also demonstrate high in vivo tumorigenicity. Physical non-participation of iCSCs in metastasis is further validated in vivo, where only mCSCs are found to exist in the metastatic sites, lymph nodes and bone marrow, whereas the primary tumor retains both iCSCs and mCSCs. However, iCSCs ensure metastasis since their presence is crucial for deliverance of highly metastatic CXCR4(+) mCSCs to the migrating fraction of cells. Cumulatively, these results unveil a novel role of iCSCs in breast cancer metastasis as parental regulators of CXCR4(+) mCSCs, and highlight the therapeutic requisite of targeting iCSCs, but not CXCR4(+) mCSCs, to restrain breast cancer metastasis from the root by inhibiting the generation of mCSCs from iCSCs. Considering the pivotal role of iCSCs in tumor metastasis, the possibility of metastasis to be a 'stem cell phenomena' is suggested.
The superconductor iron selenide (FeSe) is of intense interest owing to its unusual nonmagnetic nematic state and potential for high-temperature superconductivity. But its Cooper pairing mechanism ...has not been determined. We used Bogoliubov quasiparticle interference imaging to determine the Fermi surface geometry of the electronic bands surrounding the G = (0, 0) and X = (p/aFe, 0) points of FeSe and to measure the corresponding superconducting energy gaps. We show that both gaps are extremely anisotropic but nodeless and that they exhibit gap maxima oriented orthogonally in momentum space. Moreover, by implementing a novel technique, we demonstrate that these gaps have opposite sign with respect to each other. This complex gap configuration reveals the existence of orbital-selective Cooper pairing that, in FeSe, is based preferentially on electrons from the dyz orbitals of the iron atoms.
The structural, optoelectronics, and transport properties of TlTaO
compounds were determined utilizing the full potential augmented plane wave approach using first-principle method. We have ...considered the generalized gradient approximation for structural optimization and modified Becke-Johnson for electronic properties. The electronic properties reveal that the studied TlTaO
possesses direct bandgap of magnitude 1.52 eV. Between 0 and 12 eV, optical spectra calculations are made, taking into account the real and imaginary parts of the dielectric function, refractive index, and loss function. The transport properties are estimated considering Boltzmann transport theory. The Seebeck coefficient, electrical conductivity, thermal conductivity, and power factor are all assessed using the Boltzmann transport theory. The optimized thermoelectric response of the examined TlTaO
is produced by the improved carrier mobility, which also improves the thermoelectric efficiency of the TlTaO
. The obtained results will act as a theoretical road map for upcoming experimental and commercial TlTaO
applications.
The structural, optoelectronics, and transport properties of TlTaO3 compounds were determined utilizing the full potential augmented plane wave approach using first‐principle method. We have ...considered the generalized gradient approximation for structural optimization and modified Becke–Johnson for electronic properties. The electronic properties reveal that the studied TlTaO3 possesses direct bandgap of magnitude 1.52 eV. Between 0 and 12 eV, optical spectra calculations are made, taking into account the real and imaginary parts of the dielectric function, refractive index, and loss function. The transport properties are estimated considering Boltzmann transport theory. The Seebeck coefficient, electrical conductivity, thermal conductivity, and power factor are all assessed using the Boltzmann transport theory. The optimized thermoelectric response of the examined TlTaO3 is produced by the improved carrier mobility, which also improves the thermoelectric efficiency of the TlTaO3. The obtained results will act as a theoretical road map for upcoming experimental and commercial TlTaO3 applications.
Type-II p–n junction three-dimensional Ag2O/TiO2 microspheres have been fabricated by assembling p-type Ag2O nanoparticle on n-type TiO2 3D microsphere. Ag2O/TiO2 microsphere nanoheterojunctions were ...obtained by hydrothermal synthesis of TiO2 microspheres at 180 °C followed by photoreduction of AgNO3. The samples were carefully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), field-emission scanning electron microscopy (FESEM), and energy dispersive X-ray analysis (EDX). The photocatalytic activity toward degradation of methyl orange (MO) aqueous solution under UV light was investigated. The result showed that type-II p–n nanoheterojunctions Ag2O/TiO2 significantly enhanced the photocatalytic degradation compared to n-type TiO2 microsphere. It was found that the photocatalytic degradation followed the pseudo first-order reaction model. In particular, heterostructure with molar ratio of TiO2 and AgNO3 of 4:1 exhibited best photocatalytic activity and the corresponding apparent first-order rate constant of 0.138 min–1 which is 4 times than that of pure n-type microsphere.
Knowledge of the shape of the mass spectrum of compact objects can be used to help break the degeneracy between the mass and redshift of the gravitational wave (GW) sources and thus can be used to ...infer cosmological parameters in the absence of redshift measurements obtained from electromagnetic observations. In this paper, we study extensively different aspects of this approach, including its computational limits and achievable accuracy. Focusing on ground-based detectors with current and future sensitivities, we first perform the analysis of an extensive set of simulated data using a hierarchical Bayesian scheme that jointly fits the source population and cosmological parameters. We consider a population model (power-law plus Gaussian) which exhibits characteristic scales (extremes of the mass spectrum, presence of an accumulation point modeled by a Gaussian peak) that allow an indirect estimate of the source redshift. Our analysis of this catalog highlights and quantifies the tight interplay between source population and cosmological parameters, as well as the influence of initial assumptions (whether formulated on the source or cosmological parameters). We then validate our results by an "end-to-end" analysis using simulated GW h (t) data and posterior samples generated from Bayesian samplers used for GW parameter estimation, thus mirroring the analysis chain used for observational data for the first time in literature. Our results then lead us to re-examine the estimation of H0 obtained with GWTC-1 in Abbott et al. LIGO Scientific, Virgo Collaborations, Astrophys. J. 909, 218 (2021), and we show explicitly how population assumptions impact the final H0 result. Together, our results underline the importance of inferring source population and cosmological parameters simultaneously (and not separately as is often assumed). The only exception, as we discuss, is if an electromagnetic counterpart was to be observed for all the BBH events; then, the population assumptions have less impact on the estimation of cosmological parameters.
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