Reactive azolyl intermediates: Generation via photocatalysis and synthetic utility

We have conducted a systematic study of photocatalyst-mediated electron transfer from amines to 2-haloazoles with a particular interest in the nature, reactivity, and utility of the intermediates that can be generated. Electron transfer converts these stable molecules into reactive intermediates, whose behavior often depends entirely on the identity of the halogen that undergoes substitution. The result is both diverse chemistry and an alternative way of thinking about the chemical reactivity of these motifs. The divergent pathway is illustrated by 2-bromoazoles as well as 2-diazonium benzothiazole, which yield azolyl radicals that can be added to π-bonds. In contrast, 2-chloroazole substrates give an entirely different reaction profile, and we believe that bond formation takes place with a radical anion, rather than a radical. Under the appropriate reaction conditions, the transient reactive intermediates can be coupled with various partners to provide rapid access to new chemical methods such as alkylation, arylation and alkenylation as well as iterative synthesis of azoles and other arenes. Furthermore, since the reaction is mediated by electron transfer, minimal prefunctionalization of the coupling partners is needed, making this strategy attractive for synthesis

Comparison of hysteroscopic and laparoscopic myomectomy in large type 2 submucous leiomyomas

Background: Uterine leiomyomas are the most common benign tumors, affecting 30% of women of reproductive age. Submucous myomas are seen in 5.5-10% of all myomas. This study aimed to compare clinical, peri, and post-op outcomes of hysteroscopic and laparoscopic myomectomy in large type 2 submucous myomas. Methods: A prospective study was performed on 50 patients with large submucous type 2 leiomyomas measuring 3-5cm from October 2020 to August 2022. Patients were randomized into two groups of 25 each. Group A underwent hysteroscopic myomectomy and group B underwent laparoscopic myomectomy. Results: There was no significant difference in the demographic data of both groups except parity. Perioperative outcomes including bleeding, pain, and hospital stay were significantly higher in the laparoscopy group. None of our patients had air embolism. One patient had blindness in the postoperative period. 2 patients had uterine perforation in the hysteroscopy group. Postoperative pain was higher in the laparoscopy group. Recurrence at 3 months was seen in 2 patients of group A. Asherman syndrome was seen in group A. Single-stage success rate was seen higher in the laparoscopy group. Conclusions: Laparoscopy and hysteroscopy both are feasible techniques of myomectomy for submucous leiomyomas but for removal of large submucous leiomyomas laparoscopy myomectomy is considered better. For successful removal of large myomas in single-stage hysteroscopy, use of hysteroscopic morcellation should be considered

Ni cluster embedded (111)NiO layers grown on (0001)GaN films using pulsed laser deposition technique

(111) NiO epitaxial layers embedded with crystallographically oriented Ni-clusters are grown on c-GaN/Sapphire templates using pulsed laser deposition technique. Structural and magnetic properties of the films are examined by a variety of techniques including high resolution x-ray diffraction, precession-electron diffraction and superconducting quantum interference device magnetometry. The study reveals that the inclusion, orientation, shape, size, density and magnetic properties of these clusters depend strongly on the growth temperature (TG). Though, most of the Ni-clusters are found to be crystallographically aligned with the NiO matrix with Ni(111) parallel to NiO(111), clusters with other orientations also exist, especially in samples grown at lower temperatures. Average size and density of the clusters increase with TG . Proportion of the Ni(111) parallel to NiO(111) oriented clusters also improves as TG is increased. All cluster embedded films show ferromagnetic behaviour even at room temperature. Easy-axis is found to be oriented in the layer plane in samples grown at relatively lower temperatures. However, it turns perpendicular to the layer plane for samples grown at sufficiently high temperatures. This reversal of easy-axis has been attributed to the size dependent competition between the shape, magnetoelastic and the surface anisotropies of the clusters. This composite material thus has great potential to serve as spin-injector and spinstorage medium in GaN based spintronics of the future

SFPQ and Tau: critical factors contributing to rapid progression of Alzheimer's disease

Dysfunctional RNA-binding proteins (RBPs) have been implicated in several neurodegenerative disorders. Recently, this paradigm of RBPs has been extended to pathophysiology of Alzheimer's disease (AD). Here, we identified disease subtype specific variations in the RNA-binding proteome (RBPome) of sporadic AD (spAD), rapidly progressive AD (rpAD), and sporadic Creutzfeldt Jakob disease (sCJD), as well as control cases using RNA pull-down assay in combination with proteomics. We show that one of these identified proteins, splicing factor proline and glutamine rich (SFPQ), is downregulated in the post-mortem brains of rapidly progressive AD patients, sCJD patients and 3xTg mice brain at terminal stage of the disease. In contrast, the expression of SFPQ was elevated at early stage of the disease in the 3xTg mice, and in vitro after oxidative stress stimuli. Strikingly, in rpAD patients' brains SFPQ showed a significant dislocation from the nucleus and cytoplasmic colocalization with TIA-1. Furthermore, in rpAD brain lesions, SFPQ and p-tau showed extranuclear colocalization. Of note, association between SFPQ and tau-oligomers in rpAD brains suggests a possible role of SFPQ in oligomerization and subsequent misfolding of tau protein. In line with the findings from the human brain, our in vitro study showed that SFPQ is recruited into TIA-1-positive stress granules (SGs) after oxidative stress induction, and colocalizes with tau/p-tau in these granules, providing a possible mechanism of SFPQ dislocation through pathological SGs. Furthermore, the expression of human tau in vitro induced significant downregulation of SFPQ, suggesting a causal role of tau in the downregulation of SFPQ. The findings from the current study indicate that the dysregulation and dislocation of SFPQ, the subsequent DNA-related anomalies and aberrant dynamics of SGs in association with pathological tau represents a critical pathway which contributes to rapid progression of AD

Molecular alterations in the cerebellum of sporadic Creutzfeldt-Jakob disease subtypes with DJ-1 as a key regulator of oxidative stress

Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt-Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Twodimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 proteins in MM1 and 43 proteins in VV2 subtype to be differentially expressed. Of those, 12 proteins showed common differential expression in their expression between two subtypes. Differentially expressed proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/ oxidativestress(OS)and(iii)signaltransductionandsynaptic functions, related molecular functions. We verified 10 differentially expressed proteins at transcriptional and translational level aswell. Interestingly, protein deglycase DJ-1(an antioxidative protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Global Implications in Caring for Penile Cancer: Similarities and Divergences

Objectives: Penile cancer is a rare malignancy with a dichotomy between its incidence and evidence generation. The objective of this review is to highlight the points of consensus and divergences in penile cancer care and suggest areas where further research is needed to standardize treatment protocols. Data Sources: International guidelines and articles in PubMed and Medline were searched for studies on various aspects of penile cancer care. Conclusion: Across penile cancer care, divergences significantly outnumber similarities at present. The rarity of this disease coupled with paucity of research efforts from regions with a relatively higher incidence are the obvious reasons. The aspect with the most discrepancy is the management of inguinal nodal disease. Also, the role and sequencing of chemotherapy and radiotherapy along with surgery for the management of advanced disease needs to be defined. Collaborative research that has already begun with the establishment of the Global Society of Rare Genitourinary Tumors (GSRGT) can fill in these knowledge gaps in favor of similarities. Implications for Nursing Practice: Nurses are an integral component of the multidisciplinary team that manages patients with penile cancer. This review summarizes the different management options that might be offered to these patients due to lack of standardization and consensus. It makes the nursing fraternity aware of the various per-operative and quality-of-life issues of each management option so that they are in a position to coordinate the management pathway