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Mantle avalanches in a Venus-like stagnant lid planet

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Earth and Planetary Physics 2024年第5期8卷 686-702页

作者： Madeleine C.Kerr Dave R.Stegman Institute of Geophysics and Planetary Physics Scripps Institution of Oceanography University of California

Stagnant lid planets are characterized by a globe-encircling, conducting lid that is thick and strong, which leads to reduced global surface heat flows. Consequently, the mantles of such planets can have warmer interiors than Earth, and interestingly, a pyrolitic mantle composition under warmer conditions is predicted to have a distinctly different mantle transition zone compared to the present-day Earth(Hirose, 2002; Stixrude and Lithgow-Bertelloni, 2011; Ichikawa et al., 2014; Dannberg et al, 2022). Instead of olivine primarily transforming into its higher-pressure polymorphs such as wadsleyite and then ringwoodite, at pressures corresponding to410 km and 520 km depth in Earth, respectively, it instead transforms into a mineral assemblage of wadsleyite, majorite, and ferropericlase(WMF), and then to majorite + ferropericlase(MF), before finally transforming into bridgmanite at pressures corresponding to 660 km depth in Earth(Stixrude and Lithgow-Bertelloni, 2011; Ichikawa et al., 2014). Convective motions in stagnant lid planets are dominated by small-scale instabilities(cold drips) forming within the mobile rheological sublayer under the rigid lid. Using ASPECT and a thermodynamic model of a pyrolitic mantle composition generated by HeFESTo, we show that under certain conditions, the small drips can pond atop the WMF-MF mineral phase transition. The barrier to convective flow arises from the WMF mineral phase assemblage having an effective negative thermal expansivity(Stixrude and Lithgow-Bertelloni, 2022). Although large-scale downwellings that typically occur within mobile lid planets are able to pass through the WMF zone without difficulty(Dannberg et al., 2022; Li RP et al.,2024), the smaller and less negatively buoyant nature of downwelling drips in stagnant lid planets are more susceptible to these effects,which leads to an ephemeral layering of the mantle. Our numerical models show that in stagnant lid planets with mantle potential temperatures that exceed

关键词： Venus mantle avalanches numerical modelling phase transitions

Implementation and evaluation of Exercise is Medicine in primary care clinics within a large academic health system

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Family Medicine and Community health 2024年第1期12卷 16-27页

作者： John Kevin Ong Dayao Caroline E L Duffy Amalia M Cristiano Gene'Rusty'Kallenberg Sarah E Linke University of California San Diego School of Medicine La JollaCaliforniaUSA Milken Institute of Public health The George Washington UniversityWashingtonDistrict of ColumbiaUSA The University of Texas Medical Branch at Galveston School of Medicine GalvestonTexasUSA scripps Family Medicine Residency Scripps Mercy Hospital Chula VistaChula VistaCaliforniaUSA Herbert Wertheim School of Public health&Human Longevity Science University of California San DiegoLa JollaCaliforniaUSA Department of Family Medicine University of California San DiegoLa JollaCaliforniaUSA Omada health San FranciscoCaliforniaUSA

Objective Exercise is Medicine(EIM)is a global initiative encouraging healthcare providers to routinely assess and promote physical activity(PA)among *** objective of this study was to evaluate the feasibility,adoption,implementation and effectiveness of EIM from patient,clinician and healthcare staff perspectives using a combination of electronic health record(EHR),survey and interview *** This study used a combination of the Practical Robust Implementation and Sustainability Model(PRISM)and the Learning Evaluation model to implement *** captured from the EHR,including Physical Activity Vital Sign(PAVS)scores,and data collected from qualitative surveys and interviews were used to evaluate the programme’s Reach,Effectiveness,Adoption,Implementation,Maintenance(RE-AIM,which is embedded within PRISM)from provider,staff and patient *** Five primary care clinics within a large academic health *** A total of 24443 patients from all participating clinics had at least one PAVS score during the study period.A total of 17 clinicians completed surveys,and 4 clinicians,8 medical assistants and 9 patients completed *** Implementation fidelity metrics varied widely between components and across clinics but were generally consistent over time,indicating a high degree of programme *** was highest during the first 6 months of the COVID-19 pandemic when most visits were *** PAVS scores increased from 57.7(95%CI:56 to 59.4)to 95.2(95%CI:91.6 to 98.8)min per week at 6 months for patients not meeting PA guidelines at baseline and decreased from 253.84(95%CI:252 to 255.7)to 208.3(95%CI:204.2 to 212.4)min per week at 6 months for patients meeting PA guidelines at *** EIM implementation,clinician-estimated time spent discussing PA with patients increased for 35%of providers and stayed the same for 53%.Conclusion Overall,this study established EIM’s feasibility,adoption,implementation

关键词： routine qualitative completed

Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance

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Science China(Life Sciences) 2024年第7期67卷 1413-1426页

作者： Xueyan Chen Weilin Wu Ji-Hak Jeong Matjaz Rokavec Rui Wei Shaolong Feng Werner Schroth Hiltrud Brauch Shangwei Zhong Jun-Li Luo Department of Oncology Xiangya HospitalCentral South UniversityChangsha 410008China Department of Molecular Medicine The Scripps Research InstituteJupiter 33458USA Dr.Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart 70376Germany iFIT Cluster of Excellence University of TübingenTübingen 72074Germany The Cancer Research Institute and the Second Affiliated Hospital Henyang Medical SchoolUniversity of South ChinaHengyang 421001China National health Commission Key Laboratory of Birth Defect Research and Prevention Hunan Provincial Maternal and Child Health Care HospitalChangsha 410008China

Endocrine therapy that blocks estrogen signaling is the most effective treatment for patients with estrogen receptor positive(ER+)breast ***,the efficacy of agents such as tamoxifen(Tam)is often compromised by the development of *** we report that cytokines-activated nuclear IKKαconfers Tam resistance to ER+breast cancer by inducing the expression of FAT10,and that the expression of FAT10 and nuclear IKKαin primary ER+human breast cancer was correlated with lymphotoxinβ(LTB)expression and significantly associated with relapse and metastasis in patients treated with adjuvant ***αactivation or enforced FAT10 expression promotes Tam-resistance while loss of IKKαor FAT10 augments Tam *** induction of FAT10 by IKKαis mediated by the transcription factor Pax5,and coordinated via an IKKα-p53-miR-23a circuit in which activation of IKKαattenuates p53-directed repression of ***,our findings establish IKKα-to-FAT10 pathway as a new therapeutic target for the treatment of Tam-resistant ER+breast cancer.

关键词： nuclear IKKα breast cancer Tam-resistance FAT10 Pax5 lymphotoxin nuclear IKKα-FAT0 pathway

Stabilization and detection of labile reaction intermediates in supramolecular containers

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Chinese Chemical Letters 2024年第6期35卷 47-52页

作者： Rui Wang Yang Liang Julius Rebek Jr. Yang Yu Center for Supramolecular Chemistry&Catalysis and Department of Chemistry College of ScienceShanghai UniversityShanghai 200444China Skaggs Institute for Chemical Biology and Department of Chemistry The Scripps Research InstituteLa JollaCA 92037United States

Detection and observation of reactive intermediates is an essential step in investigation of reaction ***,most reactive intermediates are unstable and present at low concentrations;their short lifetimes make them difficult to detect and *** containers offer opportunities for the stabilization and characterization of those labile species,through isolation from the media and protection inside the cavity of the *** this review,we summarize the examples of labile reaction intermediates that are stabilized and characterized with the help of supramolecular *** container compounds include carcerands,deep cavitands and amide *** focus on unstable guest species-cyclobutadiene,benzocyclopropenone,o-benzyne,1,2,4,6-cycloheptatetraene,anti-Bredt's olefin,fluorophenoxycarbene,O-acylisoamide,and hemiaminalthat act as intermediates in certain organic reactions.

关键词： Supramolecular containers Reaction intermediates Labile species stabilization Short-lived species detection Supramolecular chemistry

Nucleation of Supercooled Water by Neutrons: Latitude Dependence and Implications for Cloud Modelling

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Atmospheric and Climate Sciences 2024年第2期14卷 221-232页

作者： Peter W. Wilson Elizabeth Wilson-Park Abraham G. Wilson Department of Physics The University at Albany SUNY Albany USA scripps Institution of Oceanography University of California San Diego USA Philanthropy Australia Sydney Australia The King’ s Institute The King&#8217s School Parramatta Australia

It has recently been shown that incident particles, neutrons, can initiate the freezing in a supercooled water volume. This new finding may have ramifications for the interpretation of both experimental data on the nucleation of laboratory samples of supercooled water and perhaps more importantly on the interpretation of ice nucleation involved in cloud physics. For example, if some fraction of the cloud nucleation previously attributed to dust, soot, or aerosols has been caused by cosmogenic neutrons, fresh consideration is required in the context of climate models. Moreover, as cosmogenic neutrons, most being muon-induced, have much greater flux at high latitudes, estimates of ice nucleates in these regions may be larger than required to accurately model cloud and condensation properties. This discrepancy has been pointed out in IPCC reports. Our paper discusses the connection between the new concept of neutrons nucleating supercooled water and the need for a new source of nucleation in high latitude clouds, ideally causing others to review current data, or to analyse future data with this idea in mind. .

关键词： Climate Models Ice Nucleation Neutrons Supercooling

Westerlies Affecting the Seasonal Variation of Water Vapor Transport over the Tibetan Plateau Induced by Tropical Cyclones in the Bay of Bengal

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Advances in Atmospheric Sciences 2024年第5期41卷 881-893页

作者： Xiaoli ZHOU Wen ZHOU Dongxiao WANG Qiang XIE Lei YANG Qihua PENG Key Laboratory of Polar Atmosphere-ocean-ice System for Weather and Climate Ministry of Education&Department of Atmospheric and Oceanic Sciences&Institute of Atmospheric SciencesFudan UniversityShanghai 200438China School of Marine Sciences Sun Yat-Sen UniversityZhuhai 519082China Institute of Deep-sea Science and Engineering Chinese Academic SciencesSanya 572000China State Key Laboratory of Tropical Oceanography South China Sea Institute of OceanologyChinese Academic ScienceGuangzhou 510301China scripps Institution of Oceanography University of CaliforniaSan DiegoLa JollaCalifornia 92093USA

This study investigates the activity of tropical cyclones(TCs)in the Bay of Bengal(BOB)from 1979 to 2018 to discover the mechanism affecting the contribution rate to the meridional moisture budget anomaly(MMBA)over the southern boundary of the Tibetan Plateau(SBTP).May and October–December are the bimodal phases of BOB TC frequency,which decreases month by month from October to December and is relatively low in ***,the contribution rate to the MMBA is the highest in *** seasonal variation in the meridional position of the westerlies is the key factor affecting the contribution *** relatively southern(northern)position of the westerlies in November and December(May)results in a lower(higher)contribution rate to the *** mechanism is confirmed by the momentum *** water vapor enters the westerlies near the trough line,the resultant meridional acceleration is directed *** follows that the farther north the trough is,and the farther north the water vapor can be *** water vapor enters the westerlies from the area near the ridge line,for Type-T(Type-R)TCs,water vapor enters the westerlies downstream of the trough(ridge).Consequently,the direction of the resultant meridional acceleration is directed south and the resultant zonal acceleration is directed east(west),which is not conducive to the northward transport of water *** is especially the case if the trough or ridge is relatively south,as the water vapor may not cross the SBTP.

关键词： tropical cyclone Tibetan Plateau Bay of Bengal moisture budget weste

A small molecule UPR modulator for diabetes identified by high throughput screening

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3983-3993页

作者： Valeria Marrocco Tuan Tran Siying Zhu Seung Hyuk Choi Ana M.Gamo Sijia Li Qiangwei Fu Marta Diez Cunado Jason Roland Mitch Hull Van Nguyen-Tran Sean Joseph Arnab K.Chatterjee Nikki Rogers Matthew S.Tremblay Weijun Shen Calibr at scripps Research The Scripps Research InstituteLa JollaCA 92037USA

Unfolded protein response(UPR) is a stress response that is specific to the endoplasmic reticulum(ER).UPR is activated upon accumulation of unfolded(or misfolded) proteins in the ER's lumen to restore protein folding capacity by increasing the synthesis of *** addition,UPR also enhances degradation of unfolded proteins and reduces global protein synthesis to alleviate additional accumulation of unfolded proteins in the ***,we describe a cell-based ultra-high throughput screening(uHTS) campaign that identifies a small molecule that can modulate UPR and ER stress in cellular and in vivo disease *** asialoglycoprotein receptor 1(ASGR) fused with Cypridina luciferase(CLuc) as reporter assay for folding capacity,we have screened a million small molecule library and identified APC655 as a potent activator of protein folding,that appears to act by promoting chaperone ***,APC655 improved pancreatic β cell viability and insulin secretion under ER stress conditions induced by thapsigargin or ***655 was also effective in preserving β cell function and decreasing lipid accumulation in the liver of the leptin-deficient(ob/ob) mouse *** results demonstrate a successful uHTS campaign that identified a modulator of UPR,which can provide a novel candidate for potential therapeutic development for a host of metabolic diseases.

关键词： βcells Unfolded protein response Small molecules Protein folding Endoplasmic reticulum Chaperones Cell signaling Diabetes ER stress Liver Pancreas Metabolic diseases

An alternative explanation for the Hf-Nd mantle array

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Science Bulletin 2017年第14期62卷 974-975页

作者： Paterno R.Castillo scripps Institution of Oceanography UCSD

The ^(176)Hf/^(177)Hf and143Nd/144Nd of mid-ocean ridge basalts(MORB)and ocean island basalts(OIB)are significantly correlated and form the so-called Hf-Nd mantle array[1,2](Fig.1a).Model calculations show that the association of OIB with the array is inconsistent with the distinctive Hf and Nd isotopic compositions of their purported ancient sediment sources in the mantle[1].A current consensus for the origin of the array is that the Lu/Hf

关键词：阵列地幔 HF 洋中脊玄武岩洋岛玄武岩

Checkpoint Inhibition in the Treatment of Unresectable,Advanced Lymphoepithelioma-like Hepatocellular Carcinoma

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 265-268页

作者： David J.Hermel Emma Z.Du Ray Lin Catherine T.Frenette Darren S.Sigal Division of Hematology and Oncology Scripps Clinic and Scripps MD Anderson Cancer CenterLa JollaCAUSA Division of Pathology Scripps Clinic and Scripps MD Anderson Cancer CenterLa JollaCAUSA Division of Radiation Oncology Scripps Clinic and Scripps MD Anderson Cancer CenterLa JollaCAUSA Division of Gastroenterology Scripps Clinic and Scripps MD Anderson Cancer CenterLa JollaCAUSA

Lymphoepithelioma-like hepatocellular carcinoma(LELHCC)is a very rare neoplasm,with distinct epidemiologic,morphologic and clinical *** mechanistic insight into the pathogenesis of this carcinoma suggests a pivotal role for the host immune system in the proliferation and progression of this ***,while detailed genomic profiling of these hepatic tumors have revealed an intra-tumoral inflammatory mutational signature that may predispose to immune checkpoint inhibitor efficacy,no published report has described their use in this tumor ***,with near 100 cases of LEL-HCC reported in the literature to date and the majority of cases confined to localized and resectable disease,current evidencebased practices in the unresectable setting are lacking,with unknown benefit of chemotherapy or *** report on the case of a 68 year-old man with unresectable,advanced LEL-HCC who had evidence of disease stability after starting on the immune checkpoint inhibitor *** disease response persisted off therapy for over a year and was potentially augmented by radiotherapy at the site of local *** this extremely rare tumor subtype,this case highlights the potential efficacy and safety of immune checkpoint blockade in LEL-HCC and reinforces the need for more robust,large-scale analysis of patients with these rare tumors to better evaluate treatment strategies and outcomes.

关键词： Immune checkpoint inhibitor Lymphoepithelioma-like hepatocellular carcinoma Stereotactic body radiation therapy Immunotherapy LEL-HCC