CATEcor: An Open Science, Shaded-Truss, Externally-Occulted Coronagraph.

We present the design of a portable coronagraph, CATEcor (where CATE stands for Continental-America Telescope Eclipse), that incorporates a novel "shaded-truss" style of external occultation and serves as a proof-of-concept for that family of coronagraphs. The shaded-truss design style has the potential for broad application in various scientific settings. We conceived CATEcor itself as a simple instrument to observe the corona during the darker skies available during a partial solar eclipse, or for students or interested amateurs to detect the corona under ideal noneclipsed conditions. CATEcor is therefore optimized for simplicity and accessibility to the public. It is implemented using an existing dioptric telescope and an adapter rig that mounts in front of the objective lens, restricting the telescope aperture and providing external occultation. The adapter rig, including occulter, is fabricated using fusion deposition modeling (FDM; colloquially "3D printing"), greatly reducing cost. The structure is designed to be integrated with moderate care and may be replicated in a university or amateur setting. While CATEcor is a simple demonstration unit, the design concept, process, and trades are useful for other more sophisticated coronagraphs in the same general family, which might operate under normal daytime skies outside the annular-eclipse conditions used for CATEcor.

The dispositional need for cognitive closure indirectly predicts mock jurors' sentencing decisions through right-wing authoritarianism.

One reason people are motivated to hold right-wing authoritarian beliefs is the need to manage uncertainty. Right-wing authoritarianism provides a stable source of black-and-white 'answers' about the social world - obey established authorities and norms and show hostility to deviants. Right-wing authoritarianism, in turn, is positively associated with more punitive attitudes and judgements. The purpose of this study was to examine the relationship between mock capital jurors' need for cognitive closure and sentencing decisions through right-wing authoritarianism. Four-hundred and fifty-one jury-eligible adults read a hypothetical capital case, weighed aggravating and mitigating evidence and chose a sentence. They also responded to items measuring right-wing authoritarianism and the need for cognitive closure. The need for cognitive closure was indirectly related to choosing a death sentence through right-wing authoritarianism and the weighing of aggravators and mitigators. Theoretical and practical implications, as well as directions for future studies, are discussed.

The SWAP Filter: A Simple Azimuthally Varying Radial Filter for Wide-Field EUV Solar Images.

We present the SWAP Filter: an azimuthally varying, radial normalizing filter specifically developed for EUV images of the solar corona, named for the Sun Watcher with Active Pixels and Image Processing (SWAP) instrument on the Project for On-Board Autonomy 2 (PROBA2) spacecraft. We discuss the origins of our technique, its implementation and key user-configurable parameters, and highlight its effects on data via a series of examples. We discuss the filter's strengths in a data environment in which wide field-of-view observations that specifically target the low signal-to-noise middle corona are newly available and expected to grow in the coming years. Supplementary Information: The online version contains supplementary material available at 10.1007/s11207-023-02183-w.

Defining the Middle Corona.

The middle corona, the region roughly spanning heliocentric distances from 1.5 to 6 solar radii, encompasses almost all of the influential physical transitions and processes that govern the behavior of coronal outflow into the heliosphere. The solar wind, eruptions, and flows pass through the region, and they are shaped by it. Importantly, the region also modulates inflow from above that can drive dynamic changes at lower heights in the inner corona. Consequently, the middle corona is essential for comprehensively connecting the corona to the heliosphere and for developing corresponding global models. Nonetheless, because it is challenging to observe, the region has been poorly studied by both major solar remote-sensing and in-situ missions and instruments, extending back to the Solar and Heliospheric Observatory (SOHO) era. Thanks to recent advances in instrumentation, observational processing techniques, and a realization of the importance of the region, interest in the middle corona has increased. Although the region cannot be intrinsically separated from other regions of the solar atmosphere, there has emerged a need to define the region in terms of its location and extension in the solar atmosphere, its composition, the physical transitions that it covers, and the underlying physics believed to shape the region. This article aims to define the middle corona, its physical characteristics, and give an overview of the processes that occur there.

The Use of mHealth Apps for the Assessment and Management of Diabetes-Related Foot Health Outcomes: Systematic Review.

BACKGROUND: Globally, diabetes affects approximately 500 million people and is predicted to affect up to 700 million people by 2045. In Australia, the ongoing impact of colonization produces inequity in health care delivery and inequality in health care outcomes for First Nations Peoples, with diabetes rates 4 times those of non-Indigenous Australians. Evidence-based clinical practice has been shown to reduce complications of diabetes-related foot disease, including ulceration and amputation, by 50%. However, factors such as a lack of access to culturally safe care, geographical remoteness, and high costs associated with in-person care are key barriers for First Nations Peoples in accessing evidence-based care, leading to the development of innovative mobile health (mHealth) apps as a way to increase access to health services and improve knowledge and self-care management for people with diabetes. OBJECTIVE: This study aims to evaluate studies investigating the use of mHealth apps for the assessment and management of diabetes-related foot health in First Nations Peoples in Australia and non-Indigenous populations globally. METHODS: PubMed, Informit's Indigenous Collection database, Ovid MEDLINE, Embase, CINAHL Complete, and Scopus were searched from inception to September 8, 2022. Hand searches of gray literature and reference lists of included studies were conducted. Studies describing mHealth apps developed for the assessment and management of diabetes-related foot health were eligible. Studies must include an evaluation (qualitative or quantitative) of the mHealth app. No language, publication date, or publication status restrictions were used. Quality appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and the Health Evidence Bulletins Wales checklists for observational, cohort, and qualitative studies. RESULTS: No studies specifically including First Nations Peoples in Australia were identified. Six studies in non-Indigenous populations with 361 participants were included. Foot care education was the main component of all mHealth apps. Of the 6 mHealth apps, 2 (33%) provided functionality for participants to enter health-related data; 1 (17%) included a messaging interface. The length of follow-up ranged from 1-6 months. Of the 6 studies, 1 (17%) reported high levels of acceptability of the mHealth app content for self-care by people with diabetes and diabetes specialists; the remaining 5 (83%) reported that participants had improved diabetes-related knowledge and self-management skills after using their mHealth app. CONCLUSIONS: The findings from this systematic review provide an overview of the features deployed in mHealth apps and indicate that this type of intervention can improve knowledge and self-care management skills in non-Indigenous people with diabetes. Future research needs to focus on mHealth apps for populations where there is inadequate or ineffective service delivery, including for First Nations Peoples and those living in geographically remote areas, as well as evaluate direct effects on diabetes-related foot disease outcomes. TRIAL REGISTRATION: PROSPERO CRD42022349087; https://tinyurl.com/35u6mmzd.

Response to OKN-007 and NAC in a Patient with Unilateral Hearing Loss and Chronic Tinnitus from Vestibular Schwannoma.

BACKGROUND: Tinnitus is the perception of sound in the absence of external acoustic stimulation. Being one of the most common diseases of the ear, it has a global prevalence ranging from 4.1 to 37.2%. To date, it has been difficult to treat tinnitus as its pathophysiology is poorly understood and there are limited treatment options. OBJECTIVE: To investigate the effect of OKN-007 (also known as HPN-07), a nitrone-based investigational drug, in combination with oral N-acetylcycsteine (NAC), for the treatment of hearing loss and chronic tinnitus under an individual expanded access protocol. PATIENT CASE: We report the case of a patient who presented with left-sided ear fullness, mild tinnitus, and mild high frequency sensorineural hearing loss with 100% word recognition. A large enhancing mass seen on MRI revealed a vestibular schwannoma. He underwent subtotal resection of the tumor resulting in a moderate-to-profound sensorineural hearing loss and catastrophic tinnitus. The patient was treated with intravenous OKN-007 at 60 mg/kg dosed three times per week and oral NAC 2500 mg twice daily. RESULTS: Post-treatment audiometric testing revealed an average of 16.66 dB in hearing threshold improvement in three frequencies (125, 250 and 500 Hz) with residual hearing in the affected left ear. His tinnitus loudness matching improved from 90 dB to 19 dB post-treatment. His Tinnitus Handicap Inventory improved from 86/100 (Catastrophic) to 40/100 (Moderate). He also experienced improvements in sleep, concentration, hearing, and emotional well-being, and reported significantly decreased levels of tinnitusrelated distress. CONCLUSIONS: This case report highlights the feasibility and therapeutic potential of the combination of OKN-007 and NAC in treating hearing loss and tinnitus that warrants further investigation.

Fluorescent Molecular Logic Gates Driven by Temperature and by Protons in Solution and on Solid.

Temperature-driven fluorescent NOT logic is demonstrated by exploiting predissociation in a 1,3,5-trisubstituted Δ2 -pyrazoline on its own and when grafted onto silica microparticles. Related Δ2 -pyrazolines become proton-driven YES and NOT logic gates on the basis of fluorescent photoinduced electron transfer (PET) switches. Additional PASS 1 and YES+PASS 1 logic gates on silica are also demonstrated within the same family. Beside these small-molecule systems, a polymeric molecular thermometer based on a benzofurazan-derivatized N-isopropylacrylamide copolymer is attached to silica to produce temperature-driven fluorescent YES logic.

Mechanistic Development and Recent Applications of the Chan-Lam Amination.

Transition metal-mediated formation of C-N bonds is an essential synthetic methodology. The discovery of the Chan-Lam amination provided a C-N bond forming process that was mild, convenient, and inexpensive, offering an alternative to complementary methods using other transition metals (TMs). Over the past 20 years, this reaction has seen considerable development in its scope of application, uptake into industry, and understanding of its mechanism. This review provides an account of the development of the Chan-Lam amination, highlighting progress and notable examples of application since 2011. Focus is given to evolution in mechanistic understanding and selected applications of the methodology within medicinal and process chemistry.

Transcriptomic profiles of non-embryogenic and embryogenic callus cells in a highly regenerative upland cotton line (Gossypium hirsutum L.).

BACKGROUND: Genotype independent transformation and whole plant regeneration through somatic embryogenesis relies heavily on the intrinsic ability of a genotype to regenerate. The critical genetic architecture of non-embryogenic callus (NEC) cells and embryogenic callus (EC) cells in a highly regenerable cotton genotype is unknown. RESULTS: In this study, gene expression profiles of a highly regenerable Gossypium hirsutum L. cultivar, Jin668, were analyzed at two critical developmental stages during somatic embryogenesis, non-embryogenic callus (NEC) cells and embryogenic callus (EC) cells. The rate of EC formation in Jin668 is 96%. Differential gene expression analysis revealed a total of 5333 differentially expressed genes (DEG) with 2534 genes upregulated and 2799 genes downregulated in EC. A total of 144 genes were unique to NEC cells and 174 genes were unique to EC. Clustering and enrichment analysis identified genes upregulated in EC that function as transcription factors/DNA binding, phytohormone response, oxidative reduction, and regulators of transcription; while genes categorized in methylation pathways were downregulated. Four key transcription factors were identified based on their sharp upregulation in EC tissue; LEAFY COTYLEDON 1 (LEC1), BABY BOOM (BBM), FUSCA (FUS3) and AGAMOUS-LIKE15 with distinguishable subgenome expression bias. CONCLUSIONS: This comparative analysis of NEC and EC transcriptomes gives new insights into the genes involved in somatic embryogenesis in cotton.

Investigation of the Middle Corona with SWAP and a Data-Driven Non-Potential Coronal Magnetic Field Model.

The large field-of-view of the Sun Watcher using Active Pixel System detector and Image Processing (SWAP) instrument onboard the PRoject for Onboard Autonomy 2 (PROBA2) spacecraft provides a unique opportunity to study extended coronal structures observed in the EUV in conjunction with global coronal magnetic field simulations. A global non-potential magnetic field model is used to simulate the evolution of the global corona from 1 September 2014 to 31 March 2015, driven by newly emerging bipolar active regions determined from Helioseismic and Magnetic Imager (HMI) magnetograms. We compare the large-scale structure of the simulated magnetic field with structures seen off-limb in SWAP EUV observations. In particular, we investigate how successful the model is in reproducing regions of closed and open structures, the scale of structures, and compare the evolution of a coronal fan observed over several rotations. The model is found to accurately reproduce observed large-scale, off-limb structures. When discrepancies do arise they mainly occur off the east solar limb due to active regions emerging on the far side of the Sun, which cannot be incorporated into the model until they are observed on the Earth-facing side. When such "late" active region emergences are incorporated into the model, we find that the simulated corona self-corrects within a few days, so that simulated structures off the west limb more closely match what is observed. Where the model is less successful, we consider how this may be addressed, through model developments or additional observational products. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11207-020-01668-2) contains supplementary material, which is available to authorized users.

Ni vs. Pd in Suzuki-Miyaura sp2-sp2 cross-coupling: a head-to-head study in a comparable precatalyst/ligand system.

The Suzuki-Miyaura reaction is a cornerstone method for sp2-sp2 cross-coupling in industry. There has been a concerted effort to enable the use of Ni catalysis as an alternative to Pd in order to mitigate cost and improve sustainability. Despite significant advances, ligand development for Ni-catalyzed Suzuki-Miyaura cross-coupling remains underdeveloped when compared to Pd and, as a consequence, ligands for Ni-catalyzed processes are typically taken from the Pd arena. In this study we evaluate the effect of using a similar Ni and Pd precatalyst based on a common bidentate ligand (dppf) in a head-to-head format for the most common type of biaryl couplings, establishing the practical implications of direct replacement of Pd with Ni, and identifying the potential origins of these observations in a mechanistic context.

Regeneration of Cochlear Hair Cells and Hearing Recovery through Hes1 Modulation with siRNA Nanoparticles in Adult Guinea Pigs.

Deafness is commonly caused by the irreversible loss of mammalian cochlear hair cells (HCs) due to noise trauma, toxins, or infections. We previously demonstrated that small interfering RNAs (siRNAs) directed against the Notch pathway gene, hairy and enhancer of split 1 (Hes1), encapsulated within biocompatible poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) could regenerate HCs within ototoxin-ablated murine organotypic cultures. In the present study, we delivered this sustained-release formulation of Hes1 siRNA (siHes1) into the cochleae of noise-injured adult guinea pigs. Auditory functional recovery was measured by serial auditory brainstem responses over a nine-week follow-up period, and HC regeneration was evaluated by immunohistological evaluations and scanning electron microscopy. Significant HC restoration and hearing recovery were observed across a broad tonotopic range in ears treated with siHes1 NPs, beginning at three weeks and extending out to nine weeks post-treatment. Moreover, both ectopic and immature HCs were uniquely observed in noise-injured cochleae treated with siHes1 NPs, consistent with de novo HC production. Our results indicate that durable cochlear HCs were regenerated and promoted significant hearing recovery in adult guinea pigs through reversible modulation of Hes1 expression. Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo.

Interrogating Pd(II) Anion Metathesis Using a Bifunctional Chemical Probe: A Transmetalation Switch.

Ligand metathesis of Pd(II) complexes is mechanistically essential for cross-coupling. We present a study of halide→OH anion metathesis of (Ar)PdII complexes using vinylBPin as a bifunctional chemical probe with Pd(II)-dependent cross-coupling pathways. We identify the variables that profoundly impact this event and allow control to be leveraged. This then allows control of cross-coupling pathways via promotion or inhibition of organoboron transmetalation, leading to either Suzuki-Miyaura or Mizoroki-Heck products. We show how this transmetalation switch can be used to synthetic gain in a cascade cross-coupling/Diels-Alder reaction, delivering borylated or non-borylated carbocycles, including steroid-like scaffolds.

Doa4 function in ILV budding is restricted through its interaction with the Vps20 subunit of ESCRT-III.

Assembly of the endosomal sorting complex required for transport (ESCRT)-III executes the formation of intralumenal vesicles (ILVs) at endosomes. Repeated cycles of ESCRT-III function requires disassembly of the complex by Vps4, an ATPase with a microtubule interaction and trafficking (MIT) domain that binds MIT-interacting motifs (MIM1 or MIM2) in ESCRT-III subunits. We identified a putative MIT domain at the N-terminus of Doa4, which is the ubiquitin (Ub) hydrolase in Saccharomyces cerevisiae that deubiquitinates ILV cargo proteins. The Doa4 N-terminus is predicted to have the α-helical structure common to MIT domains, and it binds directly to a MIM1-like sequence in the Vps20 subunit of ESCRT-III. Disrupting this interaction does not prevent endosomal localization of Doa4 but enhances the defect in ILV cargo protein deubiquitination observed in cells lacking Bro1, which is an ESCRT-III effector protein that stimulates Doa4 catalytic activity. Deletion of the BRO1 gene (bro1Δ) blocks ILV budding, but ILV budding was rescued upon disrupting the interaction between Vps20 and Doa4. This rescue in ILV biogenesis requires Doa4 expression but is independent of its Ub hydrolase activity. Thus, binding of Vps20 to the Doa4 N-terminus inhibits a non-catalytic function of Doa4 that promotes ILV formation.

Novel insights into eukaryotic γ-glutamyltranspeptidase 1 from the crystal structure of the glutamate-bound human enzyme.

The enzyme γ-glutamyltranspeptidase 1 (GGT1) is a conserved member of the N-terminal nucleophile hydrolase family that cleaves the γ-glutamyl bond of glutathione and other γ-glutamyl compounds. In animals, GGT1 is expressed on the surface of the cell and has critical roles in maintaining cysteine levels in the body and regulating intracellular redox status. Expression of GGT1 has been implicated as a potentiator of asthma, cardiovascular disease, and cancer. The rational design of effective inhibitors of human GGT1 (hGGT1) has been delayed by the lack of a reliable structural model. The available crystal structures of several bacterial GGTs have been of limited use due to differences in the catalytic behavior of bacterial and mammalian GGTs. We report the high resolution (1.67 Å) crystal structure of glutamate-bound hGGT1, the first of any eukaryotic GGT. Comparisons of the active site architecture of hGGT1 with those of its bacterial orthologs highlight key differences in the residues responsible for substrate binding, including a bimodal switch in the orientation of the catalytic nucleophile (Thr-381) that is unique to the human enzyme. Compared with several bacterial counterparts, the lid loop in the crystal structure of hGGT1 adopts an open conformation that allows greater access to the active site. The hGGT1 structure also revealed tightly bound chlorides near the catalytic residue that may contribute to catalytic activity. These are absent in the bacterial GGTs. These differences between bacterial and mammalian GGTs and the new structural data will accelerate the development of new therapies for GGT1-dependent diseases.

Detection of distinct glycosylation patterns on human γ-glutamyl transpeptidase 1 using antibody-lectin sandwich array (ALSA) technology.

BACKGROUND: γ-Glutamyl transpeptidase 1 (GGT1) is an N-glycosylated membrane protein that catabolizes extracellular glutathione and other γ-glutamyl-containing substrates. In a variety of disease states, including tumor formation, the enzyme is shed from the surface of the cell and can be detected in serum. The structures of the N-glycans on human GGT1 (hGGT1) have been shown to be tissue-specific. Tumor-specific changes in the glycans have also been observed, suggesting that the N-glycans on hGGT1 would be an important biomarker for detecting tumors and monitoring their progression during treatment. However, the large quantities of purified protein required to fully characterize the carbohydrate content poses a significant challenge for biomarker development. Herein, we investigated a new antibody-lectin sandwich array (ALSA) platform to determine whether this microanalytical technique could be applied to the characterization of N-glycan content of hGGT1 in complex biological samples. RESULTS: Our data show that hGGT1 can be isolated from detergent extracted membrane proteins by binding to the ALSA platform. Probing hGGT1 with lectins enables characterization of the N-glycans. We probed hGGT1 from normal human liver tissue, normal human kidney tissue, and hGGT1 expressed in the yeast Pichia pastoris. The lectin binding patterns obtained with the ALSA platform are consistent with the hGGT1 N-glycan composition obtained from previous large-scale hGGT1 N-glycan characterizations from these sources. We also validate the implementation of the Microcystis aeruginosa lectin, microvirin, in this platform and provide refined evidence for its efficacy in specifically recognizing high-mannose-type N-glycans, a class of carbohydrate modification that is distinctive of hGGT1 expressed by many tumors. CONCLUSION: Using this microanalytical approach, we provide proof-of-concept for the implementation of ALSA in conducting high-throughput studies aimed at investigating disease-related changes in the glycosylation patterns on hGGT1 with the goal of enhancing clinical diagnoses and targeted treatment regimens.