Broad Groups Research Articles

Short Total Synthesis of (+)-Colletotryptins B-D and Mucronatin B Derivative.

The short and first total synthesis of (+)-colletotryptins B-D, ent-colletotryptin A, and diastereomer of mucronatin B, which are a group of natural 3-(indol-2-yl)-3-(indol-3-yl)-1,2-propanediol (IIPDO) analogues containing two stereogenic centers at the C8' and C9' positions, isolated from endophytic fungus Colletotrichum sp. SC1355 and Tetrapterys mucronata, respectively, has been successfully accomplished in two and three steps with overall yields ranging from 28 to 54%. Key features of this synthesis include an innovative Bi(OTf)3-catalyzed stereoselective transindolylation of (S)-3,3'-di(1H-indol-3-yl)propane-1,2-diol. The operational simplicity, environmentally friendly catalyst, and broad functional group tolerance of this modular strategy render it suitable for adoption in both academic and industrial settings.

Mapping emergent coral reefs: a comparison of pixel‐ and object‐based methods

AbstractAlthough emergent coral reefs represent a significant proportion of overall reef habitat, they are often excluded from monitoring projects due to their shallow and exposed setting that makes them challenging to access. Using drones to survey emergent reefs overcomes issues around access to this habitat type; however, methods for deriving robust monitoring metrics, such as coral cover, are not well developed for drone imagery. To address this knowledge gap, we compare the effectiveness of two remote sensing methods in quantifying broad substrate groups, such as coral cover, on a lagoon bommie, namely a pixel‐based (PB) model versus an object‐based (OB) model. For the OB model, two segmentation methods were considered: an optimized mean shift segmentation and the fully automated Segment Anything Model (SAM). Mean shift segmentation was assessed as the preferred method and applied in the final OB model (SAM exhibited poor identification of coral patches on the bommie). While good cross‐validation accuracies were achieved for both models, the PB had generally higher overall accuracy (mean accuracy PB = 75%, OB = 70%) and kappa (mean kappa PB = 0.69, OB = 0.63), making it the preferred method for monitoring coral cover. Both models were limited by the low contrast between Coral features and the bommie substrate in the drone imagery, causing indistinct segment boundaries in the OB model that increased misclassification. For both models, the inclusion of a drone‐derived digital surface model and multiscale derivatives was critical to predicting coral habitat. Our success in creating emergent reef habitat models with high accuracy demonstrates the niche role drones could play in monitoring these habitat types, which are particularly vulnerable to rising sea surface and air temperatures, as well as sea level rise which is predicted to outpace reef vertical accretion rates.

Political (de)modernization of Russia in the 1990s: turning events and models of conflict dynamics

A set of theoretical models are presented to explain the complex political dynamics in Russia in the 1990s.The parametric model is used to analyze the fluctuations of the political system in a conditional space defined by two axes: the scale of collegial division of power (CDP) and the level of state success. Major turning events as closely related structural changes shift the state of the political system along bothaxes. Political modernization occurs when success and CDP rise, while demodernization is defined as a decline on one or both scales. The contours model combines structure and agency processes and takes into account two contours of political dynamics. In the large - socio-political - contour, turning events affect grassroot structures and processes related to objective conditions of life, subjective moods, and behavioral attitudes of broad groups of the population. In the small contour (interactions of political actors with their rivalry and conflicts) the same turning events change the balance of power of the main players in national politics. The general principles of the dynamics of the CDP, state success in their interrelation, as a result of turning events as a consequence of the interaction of actors in the small loop under the influence of processes in the large loop are formulated. A step-by-step model explaining the natural shift to authoritarianism on the basis of these principles and under special conditions is proposed. Through these models, the mechanisms of conflict dynamics and socio-political processes of the 1990s in Russia are presented, when the processes of political modernization began to be combined with and then replaced by trends of demodernization.

Psychological Therapy for Functional Neurological Disorder: Examining Impact on Dissociation, Psychological Distress and General Functioning

ABSTRACT Functional neurological disorder (FND) represents a broad group of motor and sensory clinical symptoms which cannot be explained by other neurological diagnoses. Dissociation is considered a key mechanism in their development and maintenance. Despite psychological therapy being the recommended choice of treatment for FND, evidence for its effectiveness is in its infancy. This study explored the dissociative profile of forty-seven patients with FND and evaluated whether individual psychological therapy improved dissociative symptoms, psychological distress and general functioning among twenty-five adults with FND. Patients completed the Multiscale Dissociation Inventory, the EuroQol five-dimensional descriptive system, the General Anxiety Disorder-7 scale and the Patient Health Questionnaire-9. Our sample showed high levels of disengagement, depersonalization and memory disturbance at baseline. Treatment was associated with significant improvements in general functioning, and symptoms of dissociation and anxiety. Improvements in dissociative experiences were found to be possibly due to reduction in anxiety. Improvements in depression were the strongest predictor of improvements in general functioning. Limitations and areas for further research are discussed.

How do the Substance Abuse and Mental Health Services Administration's Technology Transfer Centers Decide What Evidence-Based Practices to Disseminate and Determine How to Do So? A Cross-Sectional Study of a National Network.

It is important to use evidence-based programs and practices (EBPs) to address major public health issues. However, those who use EBPs in real-world settings often require support in bridging the research-to-practice gap. In the US, one of the largest systems that provides such support is the Substance Abuse and Mental Health Services Administration's (SAMHSA's) Technology Transfer Center (TTC) Network. As part of a large external evaluation of the Network, this study examined how TTCs determine which EBPs to promote and how to promote them. Using semi-structured interviews and pre-testing, we developed a "Determinants of Technology Transfer" survey that was completed by 100% of TTCs in the Network. Because the study period overlapped with the onset of the COVID-19 pandemic, we also conducted a retrospective pre/post-pandemic comparison of determinants. TTCs reported relying on a broad group of factors when selecting EBPs to disseminate and the methods to do so. Stakeholder and target audience input and needs were consistently the most important determinant (both before and during COVID-19), while some other determinants fluctuated around the pandemic (e.g., public health mandates, instructions in the funding opportunity announcements). We discuss implications of the findings for technology transfer and frame the analyses in terms of the Interactive Systems Framework for Dissemination and Implementation.

Visible-Light-Promoted [4π + 2σ] Annulation of Dienes and Alkylamines via Dual Inert C(sp3)-H Bond Activation.

Herein, visible-light-promoted [4π + 2σ] annulation of dienes and alkylamines was achieved via dual C(sp3)-H bond functionalization of alkylamines. The elusive enamine precursors are generated under mild conditions by photoredox catalysis, efficiently annulated by the diene, and simultaneously functionalized with two aliphatic C(sp3)-H bonds, resulting in the productive synthesis of new aromatic rings. The aromatic ring construction provides direct access to 2-hydroxybenzophenone derivatives in high yields (up to 90%). This [4π + 2σ] annulation reaction demonstrates mild reaction conditions, high reaction efficiency, and broad functional group tolerance, and this synthetic protocol has been made available for the late-stage transformation of natural products and commercial drugs.

Examining the relationship between disciplinary counterspaces for undergraduate women and sense of belonging: A physics exemplar

AbstractFor students who face marginalization in a discipline, counterspaces are safe spaces of refuge that allow them to express their multiple identities and foster their sense of belonging. While prior qualitative work on counterspaces has highlighted how and why these spaces support marginalized students, there is little quantitative work that provides systemic evidence on broad counterspace initiatives formed to support students' disciplinary sense of belonging. In physics, a discipline that is deeply androcentric, two potential counterspaces have emerged for undergraduate women: the Conferences for Undergraduate Women in Physics (CUWiP) and Women in Physics Groups (WiPG). Drawing on survey data collected from undergraduate women in physics programs across the country who were registering for the 2018 CUWiP (N = 1388), we used structural equation modeling to test the effect of earlier participation in CUWiP and WiPG on students' current sense of belonging and interest in physics. We also tested the mediating effect of believing that there are serious gender issues in physics since these spaces have been found to increase students' consciousness of gender bias. The results revealed a significant positive direct effect of CUWiP and WiPG on sense of belonging. A more complex story emerged for indirect effects where believing in serious gender issues can negatively affect sense of belonging if interest in physics is not positively reinforced. Overall, the findings clearly provide quantitative evidence that broad diversity conference and affinity group initiatives, such as CUWiP and WiPG, can act as counterspaces that bolster belonging for women in disciplines like physics where they are marginalized. However, activities in these spaces should also continue to foster students' unique disciplinary interests.

Titanium catalyzed [2σ + 2π] cycloaddition of bicyclo[1.1.0]-butanes with 1,3-dienes for efficient synthesis of stilbene bioisosteres

Natural stilbenes have shown significant potential in the prevention and treatment of diseases due to their diverse pharmacological activities. Here we present a mild and effective Ti-catalyzed intermolecular radical-relay [2σ + 2π] cycloaddition of bicyclo[1.1.0]-butanes and 1,3-dienes. This transformation enables the synthesis of bicyclo[2.1.1]hexane (BCH) scaffolds containing aryl vinyl groups with excellent regio- and trans-selectivity and broad functional group tolerance, thus offering rapid access to structurally diverse stilbene bioisosteres.

Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells.

Therapeutic genome editing of haematopoietic stem cells (HSCs) would provide long-lasting treatments for multiple diseases. However, the in vivo delivery of genetic medicines to HSCs remains challenging, especially in diseased and malignant settings. Here we report on a series of bone-marrow-homing lipid nanoparticles that deliver mRNA to a broad group of at least 14 unique cell types in the bone marrow, including healthy and diseased HSCs, leukaemic stem cells, B cells, T cells, macrophages and leukaemia cells. CRISPR/Cas and base editing is achieved in a mouse model expressing human sickle cell disease phenotypes for potential foetal haemoglobin reactivation and conversion from sickle to non-sickle alleles. Bone-marrow-homing lipid nanoparticles were also able to achieve Cre-recombinase-mediated genetic deletion in bone-marrow-engrafted leukaemic stem cells and leukaemia cells. We show evidence that diverse cell types in the bone marrow niche can be edited using bone-marrow-homing lipid nanoparticles.

Occurrence of legacy and Emerging per- and polyfluoroalkyl substances (PFASs) in indoor dust from office environment in south china

Per- and polyfluoroalkyl substances (PFASs) constitute a broad group of fluorinated organic chemicals that are widely used in consumer products and industrial applications due to their excellent physicochemical properties. Given that people spend a significant portion of their time in office environments, our understanding of the environmental presence and human exposure to these chemicals is crucial. In this study, we conducted a targeted analysis of 24 PFASs in office indoor environments. The ΣPFAS concentrations ranged from 51.6 to 219 ng/g with mean (±SE) and median concentrations of 114 (±5.75) and 107 ng/g, respectively. Hexafluoropropylene oxide dimer acid (HFPO-DA) was the most abundant emerging PFAS detected in the dust, with mean and median concentrations of 40.5 (±1.62) and 40.4 ng/g, respectively, comprising 34.2 % of the ΣPFAS concentrations. Notably, HFPO-DA exhibited a positive correlation with perfluorooctane sulfonate (PFOS) (r: 0.427, p < 0.01), suggesting a potential common source for these two compounds. Our findings underscore the significant contribution of emerging PFASs to total PFAS concentrations and raise concerns about their chronic toxicity and potential health risks to humans in office indoor environments.

Electrochemical Allylic C(sp3)-H Isothiocyanation via [3,3]-Sigmatropic Rearrangement.

The direct allylic C(sp3)-H functionalization provides a straightforward protocol for the synthesis of valuable molecules. We report herein the first chemo- and site-selective method for allylic C(sp3)-H isothiocyanation of various internal alkenes under mild electrochemical conditions. This method exhibits broad functional group tolerance and excellent selectivity and can be applied for late-stage isothiocyanation of bioactive molecules. Combined experimental and computational studies indicate that the reaction proceeds via an unexpected [3,3]-sigmatropic rearrangement.

Impact of Trade Liberalisation and MSME Classification on Productivity of Indian Manufacturing Firms

This article examines the effects of tariff and non-tariff reductions on firm-level productivity of large as well as Micro, Small and Medium Enterprises (MSMEs) in India’s manufacturing sector for the 1999–2009 period. We calculate input and final goods tariffs, effective rates of protection and non-tariff barriers (NTBs) for broad product groups using information from India’s Exim Policy of 1997–2003 and 2004–2009 to examine this impact. We use a balanced as well as unbalanced firm-level panel data set, while accounting for firm, industry, state and time-specific factors. By using fixed effect models and Heckman’s two-step estimation procedure, we find that trade liberalisation is associated with improved firm-level productivity for large firms but not in the case of MSMEs. We posit that this might be due to the relative disadvantages that Indian MSMEs face which prevent them from benefiting from trade liberalisation. We also find that productivity gains arising from the sourcing of imported inputs have been greater than those arising from increased product competition and that NTB liberalisation has had a greater impact compared to tariff liberalisation on firm-level productivity. Changes in MSME legislation and the classification of firms are also found to have a bearing on firm performance. Our study contributes to the literature by confirming the need to focus specifically on constraints faced by MSMEs if they are to benefit from trade liberalisation. It highlights the importance of liberalising trade in intermediates as well as the role of MSME classification in enabling productivity gains. JEL Codes: L6, D24, L1, F13

Exploring the influence of activity participation on the economic value of nature-based recreation in the Sierra Nevada

A more comprehensive understanding of how recreational values and forest visitation rates vary across different activities enables forest managers to tailor conservation and management strategies to align with preferences among visitors, ensuring more effective allocation of budgetary resources. However, current research often focuses on only a few recreational activities, resulting in limited insights for forest managers. This study aims to expand the nature-based activities considered so that management can better serve the broader public. We conduct a travel cost analysis using a large survey-based dataset to estimate the value of nature-based recreation in national forests in the Sierra Nevada region and assess how these values differ across main activities. We categorize recreational activities into five broad groups (Passive, Active, Camping, Winter, and Other) to offer a comprehensive view of recreational preferences. A truncated negative binomial regression accounting for endogenous stratification is used to analyze the relationship between the number of trips to the forests, travel cost, activity categories, and socio-demographic variables. Our results suggest a mean consumer surplus (CS) of $65 per visit per person to national forests in the Sierra Nevada. Aggregated over annual per person visits, the total CS is approximately $313.3 million per year. Our findings reveal variations in CS across activity groups, with winter activities (e.g., skiing, snowboarding) and active activities (e.g., hiking, fishing) attracting the highest number of visits, and the highest total CS. Our results provide valuable insights for national forest managers, facilitating the strategic allocation of limited resources to recreational activities that maximize societal welfare.

New task-new results? How the gaze cone is influenced by the method of measurement.

Perceiving direct gaze-the perception of being looked at-is important in everyday life. The gaze cone is a concept to define the area in which observers perceive gaze as direct. The most frequently used methods to measure direct gaze threshold fall into two broad groups: First, a variant of the method of constant stimuli, firstly introduced by Gibson and Pick (The American Journal of Psychology, 76, 386-394, 1963). Second, a variant of the method of adjustment, firstly introduced by Gamer and Hecht (Journal of Experimental Psychology: Human Perception and Performance, 33, 705-715, 2007). Previous studies found a considerable range of thresholds, and although some influences on thresholds are already known (uncertainty, clinical groups), thresholds often vary for no apparent reason. Another important method is a triadic gaze-perception task, which usually finds triadic gaze direction judgments to be overestimated. In two experiments, we compare the method of adjustment with the method of constant stimuli. Experiment 1additionally examines the influence of the overestimation effect found in the triadic task. Results indicate that thresholds are larger when measured by the method of adjustment than by constant stimuli. Furthermore, Experiment 1finds a nonlinear overestimation factor, indicating that gaze directions near 0° are less overestimated than larger eccentricities. Correcting the thresholds with individually obtained overestimation factors widens the gaze cone but does not eliminate the average difference between the methods of adjustments and constant stimuli.

Lewis Acid-Catalyzed Formal [4 + 2] Reaction of Alkynyl Sulfides and 2-Pyrones To Access Polysubstituted Aryl Sulfides.

A practical and efficient method to access polysubstituted aryl sulfides has been discovered via a Lewis acid-catalyzed reaction between alkynyl sulfide and 2-pyrone, involving a Diels-Alder/retro-Diels-Alder pathway. Alkynyl sulfide as an electron-rich dienophile and 2-pyrones as electron-poor dienes are conjunctively transformed into a series of polysubstituted aryl sulfides with broad functional group compatibility in good to excellent yields (40 examples, 43-88% yield). The robustness and practicality of the protocol has been demonstrated through gram-scale synthesis and the ease of transformation of the resulting products.

Hydroxylamine-Mediated C(sp2)-H Trifluoromethylation of Terminal Alkenes.

Introduction of the trifluoromethyl (CF3) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine-mediated radical process for C(sp2)-H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late-stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway.

Photosynthesis of C-1-Deuterated Aldehydes via Chlorine Radical-Mediated Selective Deuteration of the Formyl C-H Bond.

C-1-deuterated aldehydes are essential building blocks in the synthesis of deuterated chemicals and pharmaceuticals. This has led chemists to devise mild methodologies for their efficient production. Ideally, hydrogen-deuterium exchange (HDE) is the most effective approach. However, the traditional HDE for creating C-1-deuterated aldehydes often requires a complex system involving multiple catalysts and/or ligands. In this study, we present a mild photocatalytic HDE of the formyl C-H bond with D2O. This process is facilitated by chlorine radicals that are generated in situ from low-cost FeCl3. This strategy demonstrated a broad reaction scope and high functional group tolerance, affording good yields and ≤99% D incorporation. To bridge the gap between research and industrial applications, we designed a new flow photoreactor equipped with a high-intensity light-emitting diode bucket, enabling the synthesis of C-1-deuterated aldehydes on a scale of 85 g. Finally, we successfully produced several important deuterated aldehydes that are integral to the synthesis of deuterated pharmaceuticals.

Carbon–nitrogen transmutation in polycyclic arenol skeletons to access N-heteroarenes

Developing skeletal editing tools is not a trivial task, and realizing the corresponding single-atom transmutation in a ring system without altering the ring size is even more challenging. Here, we introduce a skeletal editing strategy that enables polycyclic arenols, a highly prevalent motif in bioactive molecules, to be readily converted into N-heteroarenes through carbon–nitrogen transmutation. The reaction features selective nitrogen insertion into the C–C bond of the arenol frameworks by azidative dearomatization and aryl migration, followed by ring-opening, and ring-closing (ANRORC) to achieve carbon-to-nitrogen transmutation in the aromatic framework of the arenol. Using widely available arenols as N-heteroarene precursors, this alternative approach allows the streamlined assembly of complex polycyclic heteroaromatics with broad functional group tolerance. Finally, pertinent transformations of the products, including synthesis complex biheteroarene skeletons, were conducted and exhibited significant potential in materials chemistry.

Abstract PO5-01-04: HER2 Amplification Level and Focal/Broad Region Size as Predictors of Treatment Response in Neoadjuvant Chemotherapy and Anti-HER2 Therapy for HER2-Positive Breast Cancer

Abstract Background: Neoadjuvant chemotherapy combined with anti-HER2 therapy has become the standard treatment approach for HER2-positive breast cancer. However, not all HER2-positive patients can achieve pathological complete response after neoadjuvant therapy. This raises the question of which subset of HER2+ patients derive the greatest benefit from pre-operative HER2-targeted treatment. Therefore, this study aims to determine whether the level and amplification region size of HER2 amplification are associated with the efficacy of neoadjuvant chemotherapy combined with anti-HER2 therapy. Methods: A total of 523 breast cancer samples were collected from 2017 to 2018, among which 202 cases were HER2-positive patients. Among these, 55 HER2-positive patients received neoadjuvant chemotherapy combined with anti-HER2 targeted therapy. The amplification status of HER2 was assessed using immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) and next-generation sequencing (NGS). The HER2/CEP17 ratio, determined by FISH, was used to represent the amplification level of HER2. The size of the amplification region was calculated using NGS and neighboring genes located in chr17q. Amplification regions smaller than 1 Mb were classified as focal amplification, while those larger than 1 Mb were classified as broad amplification. Results: We compared the HER2/ERBB2 status of 523 breast cancer patients using different detection methods and found a high concordance between ERBB2 amplification detected by NGS and HER2-positivity detected by IHC and FISH, with a sensitivity of 96.0%, specificity of 97.8%, and overall concordance of 97.1%. Based on the HER2/CEP17 ratio determined by FISH, we observed that using a threshold of 6 for classification, the high amplification group had a significantly higher pCR rate compared to the low amplification group (86.7% vs. 41.7%; p=0.037, odds ratio [OR]=0.121, 95% confidence interval [CI]: 0.009-0.919). Moreover, the focal amplification group showed a higher pCR rate compared to the broad amplification group (65.9% vs. 30.8%, p=0.051, OR=0.237, 95% CI: 0.045-1.035). Additionally, within the low amplification group (HER2/CEP17 &amp;lt; 6), the pCR rate was 66.7% for focal amplification and 20% for broad amplification, suggesting that focal amplification of ERBB2 may further guide clinical benefit in the low HER2/CEP17 ratio group. Conclusion: This study demonstrates a high concordance between ERBB2 amplification determined by NGS and HER2-positivity determined by IHC/FISH. High HER2/CEP17 ratio and focal amplification of ERBB2 are associated with a higher pCR rate in neoadjuvant chemotherapy combined with anti-HER2 targeted therapy. Citation Format: Ning Liao, Guochun Zhang, Xinze Lv, Kai Li, Ting Hou, Zhou Zhang. HER2 Amplification Level and Focal/Broad Region Size as Predictors of Treatment Response in Neoadjuvant Chemotherapy and Anti-HER2 Therapy for HER2-Positive Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-04.

Photoinduced Palladium-Catalyzed Radical Heck-Type Coupling of Cyclobutanone Oxime Esters with Vinyl Arenes.

A palladium-catalyzed radical Heck-type coupling reaction of cyclobutanone oxime esters with olefins under visible-light irradiation has been developed. The cyanoalkyl/Pd(I) hybrid species generated by selected ring-opening C-C bond cleavage of imino/Pd(I) species reacted smoothly with vinyl arenes, delivering the cyanoalkylation olefins under mild conditions. This elegant strategy has a broad scope and functional group tolerance. Subsequently, late-stage functionalization of bioactive molecules and synthetic transformations of the product further confirm the practicality.