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New therapies for relapsed castration-resistant prostate cancer based on peptide analogs of hypothalamic hormones

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Asian Journal of Andrology 2015年第6期17卷 925-928页

作者： andrew v Schally veterans Affairs Medical Center and South Floridaveterans Affairs Foundation for Research andEducation Miami FL 33125 USA Department of Pathology University of Miami Miller School ofMedicine Miami FL 33136 USA Department of Medicine Division of Hematology/Oncology Universityof Miami Miller School of Medicine Miami FL33136 USA Department of Medicine Division of Endocrinology University of Miami Miller School ofMedicine Miami FL 33136 USA Department of Medicine Sylvester Comprehensive Cancer CenterUniversity of Miami Miller School of Medicine MiamiFL 33136 USA Department of Urology HerbertWertheim College of Medicine Florida InternationalUniversity Miami FL 33174 USA.

Itis a pleasure to contribute our presentation at the International Prostate Forum of the Annual Meeting of the American Urological Association （AUA） to this special issue of the Asian Journal of Andrology. We are gratified that the method developed in our laboratories1 based on agonistic analogs of hypothalamic luteinizing hormone-releasing hormone （LHRH）, also called gonadotropin which was discovered releasing hormone, and characterized by one of us （AvS） in the 1970S, has been used since the early 1980s for the treatment of hormone-dependent prostate cancer.

关键词： therapies castration hormones

The Trace Element Distribution Patterns of Ediacaran-Early Cambrian Black Shales and the Origin of Selenium in the Guangning Area, Western Guangdong Province, South China

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Acta Geologica Sinica(English Edition) 2017年第6期91卷 1978-1991页

作者： TIAN Xinglei LUO Kunli andrew v.ZUZA Institute of Geographic Sciences and Natural Resources Research Chinese Academy of Sciences University of the Chinese Academy of Sciences Nevada Bureau of Mines and Geology University of Nevada

The Ediacaran and early Cambrian black shales are widespread across the South China Craton （Yangtze and Cathaysia blocks）. However, the trace element distribution patterns of the Ediacaran and early Cambrian black shales in the Cathaysia Block are still unclear. In this study, thirty- four black shale samples in the Lechangxia Group （Ediacaran） and thirteen black shale samples in the lower Bacun Group （early Cambrian） from Guangning area, western Guangdong Province, South China, were analyzed for major and trace elements concentrations. Compared to the upper continental crust, the Ediacaran black shales exhibit strongly enriched Se, Ga, and As with enrichment factor values （EF） higher than 10, significantly enrichedBi and Rb （10〉EF〉5）, weakly enriched Mo, Ba, Cs, v, In, Be, TI, and Th （5〉EF〉2）, normal U, Cr, Cd, Sc, Pb, Cu, and Li （2〉EF〉0.5）, and depleted Ni, Zn, Sr, and Co. Early Cambrian black shales display strongly enriched Se, Ga, and As, significantly enriched Ba, Bi, and Rb, weakly enriched Mo, Cs, Cd, v, U, Be, In, and TI, normal Sc, Th, Cr, Li, Cu, Ni, and Pb and depleted Co, Zn, and Sr. Moreover, Se is the most enriched trace element in the Ediacaran and early Cambrian black shales： concentrations vary from 0.25 to 30.09 ppm and 0.54 to 5.01 ppm, and averaging 4.84 and 1.72 ppm, with average EF values of 96.87 and 34.32, for the Ediacaran and early Cambrian shales respectively. The average concentration of Se in the Ediacaran black shales is 2.8 times higher than that of early Cambrian black shales. Se contents in the Ediacaran and early Cambrian black shales exhibit significant variation （P = 0.03）. Provenance analysis showed that Se contents of both the Ediacaran and early Cambrian black shales were without detrital provenance and volcanoclastic sources, hut of hydrothermal origin. The deep sources of Se and the presence of pyrite may explain the higher Se contents in the Ediacaran black shales. Similar with the Se-rich characteristics of the contemporan

关键词： black shale selenium Ediacaran and early Cambrian Guangning area Cathaysia block

Geologic field evidence for non-lithostatic overpressure recorded in the North American Cordillera hinterland,northeast Nevada

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Geoscience Frontiers 2022年第2期13卷 471-490页

作者： andrew v.Zuza Drew A.Levy Suzanne R.Mulligan Nevada Bureau of Mines and Geology University of NevadaRenoNV 89557USA Department of Geoscience University of NevadaLas VegasNV 89154USA

There is a long-standing discrepancy for numerous North American Cordillera metamorphic core complexes between geobarometric pressures recorded in the exhumed rocks and their apparent burial depths based on palinspastic reconstructions from geologic field *** particular,metamorphic core complexes in eastern Nevada are comprised of well-documented~12-15 km thick Neoproterozoic-Paleozoic stratigraphy of Laurentia’s western passive margin,which allows for critical characterization of field *** this contribution we focus on the Ruby Mountain-East Humboldt Range-Wood Hills-Pequop Mountains(REWP)metamorphic core complex of northeast Nevada to explore reported peak pressure estimates versus geologic field relationships that appear to prohibit deep *** high pressure estimates of 6-8 kbar(23-30 km depth,if lithostatic)from the lower section of the Neoproterozoic-Paleozoic passive margin sequence require burial and or repetition of the passive margin sequence by 2-3×stratigraphic *** observations from the least migmatized and/or mylonitized parts of this complex,including field observations,a transect of peak-temperature(T_(p))estimates,and critical evaluation of proposed thickening/burial mechanisms cannot account for such deep *** Neoproterozoic-Cambrian(€)rocks part of a continuous stratigraphic section that transitions~8 km upsection to unmetamorphosed Permian strata that were not buried,we obtained new quartz-in-garnet barometry via Raman analysis that suggest pressures of~7 kbar(~26 km).A T_(p)traverse starting at the same basal€rocks reveals a smooth but hot geothermal gradient of≥40℃/km that is inconsistent with deep *** observation is clearly at odds with thermal gradients implied by high P-T estimates that are all≤25℃/*** similar discrepancies between pressure estimates and field observations have been discussed for the northern Snake Range metamorphic core complex,~200 km to the *** argue that

关键词： Non-lithostatic pressure Tectonic overpressure North American Cordillera Ruby Mountain-East Humboldt Range Peak temperature Geothermal gradient

STAT3 and sphingosine-1-phosphate in inflammation-associated colorectal cancer

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World Journal of Gastroenterology 2014年第30期20卷 10279-10287页

作者： andrew v Nguyen Yuan-Yuan Wu Elaine Y Lin Department of Biological Sciences and Geology Queensborough-CUNYBaysideNY 10461United States Department of Pathology Montefiore Medical CenterAlbert Einstein College of MedicineBronxNY 10461United States Department of Medicine Einstein Cancer CenterAlbert Einstein College of MedicineBronxNY 10461United States

Accumulated evidences have demonstrated that signal transducer and activator of transcription 3(STAT3)is a critical link between inflammation and *** studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer(CRC)is associated with sphingosine-1-phosphate(S1P)receptor *** inflammatory response whereby interleukin(IL)-6 production is abundant,STAT3-mediated pathways were found to promote the activation of sphingosine kinases(SphK1and SphK2)leading to the production of ***,S1P encourages the activation of STAT3 through a positive autocrine-loop *** crosstalk between IL-6,STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed *** targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC.

关键词： Sphingosine-1-phosphate Signal transducer and activator of transcription 3 Interleukin-6 Inflammation Colorectal cancer Tumorigenesis Tumor progression Inflammatory bowel disease

Spinal cord infarction attributed to SARS-Cov-2, with post-acute sequelae of COvID-19: A case report

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World Journal of Clinical Cases 2023年第36期11卷 8542-8550页

作者： Christina v Oleson andrew C Olsen Suzanna Shermon Department of Physical Medicine and Rehabilitation Case Western Reserve UniversityMetroHealth Rehabilitation InstituteClevelandOH 44109United States

BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-Cov-2),spinal cord infarction or ischemia has been extremely *** of long coronavirus disease(COvID)in this select population have not been *** SUMMARY We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction,attributed to acute infection with *** work up confirmed a T3 complete(ASIA impairment Scale A)paraplegia resulting from a thrombotic *** reported myalgias,neuropathic pain,spasticity,bladder spasms,and urinary tract infections exceeded the frequency and severity of many spinal cord injury(SCI)individuals of similar age and degree of neurologic *** her first year after contracting COvID-19,she underwent 2 separate inpatient rehabilitation courses,but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled *** other complications of complete non-traumatic SCI(NTSCI),including neurogenic bowel and temperature hypersens-itivity,were mild,and pressure injuries were *** has now transitioned from the acute to chronic phase of spinal cord injury care,with subsequent development of post-acute sequelae of SARS-Cov-2 infection(PASC).CONCLUSION This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COvID-19,with subsequent progression to *** Tip:Although stroke and venous thromboembolism have been frequently observed with acute coronavirus disease 2019(COvID-19),spinal cord infarction leading to paraplegia has rarely been *** report a case of spinal cord infarction shortly following infection with severe acute respiratory syndrome coronavirus 2(SARS-Cov-2).Consequently,this individual has experienced severe neurologic disability,with subsequent developme

关键词： Spinal cord infarction Paraplegia COvID-19 SARS-Cov-2 Post-acute

Gaussian process analysis of electron energy loss spectroscopy data:multivariate reconstruction and kernel control

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npj Computational Materials 2021年第1期7卷 1395-1404页

作者： Sergei v.Kalinin andrew R.Lupini Rama K.vasudevan Maxim Ziatdinov Center for Nanophase Materials Sciences Oak Ridge National LaboratoryOak RidgeTNUSA

Advances in hyperspectral imaging including electron energy loss spectroscopy bring forth the challenges of exploratory and physics-based analysis of multidimensional data *** multivariate linear unmixing methods generally explore similarities in the energy dimension,but ignore correlations in the spatial *** the same time,Gaussian process(GP)explicitly incorporate spatial correlations in the form of kernel functions but is computationally ***,we implement a GP method operating on the full spatial domain and reduced representations in the energy *** this multivariate GP,the information between the components is shared via a common spatial kernel structure,while allowing for variability in the relative noise magnitude or image *** explore the role of kernel constraints on the quality of the reconstruction,and suggest an approach for estimating them from the experimental *** further show that spatial information contained in higher-order components can be reconstructed and spatially localized.

关键词： domain kernel multivariate

Genomic analysis uncovers functional variation in the C-terminus of anthocyanin-activating MYB transcription factors

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Horticulture Research 2021年第1期8卷 885-898页

作者： Jessica A.Rodrigues Richard v.Espley andrew C.Allan The New Zealand Institute for Plant and Food Research Limited 120 Mount Albert RoadSandringhamAuckland 1025New Zealand School of Biological Sciences University of Auckland3A Symonds StAuckland 1010New Zealand

MYB transcription factors regulate diverse aspects of plant development and secondary metabolism,often by partnering in transcriptional regulatory ***,we harness genomic resources to identify novel MYBs,thereby producing an updated eudicot MYB phylogeny with revised relationships among subgroups as well as new information on sequence variation in the disordered C-terminus of anthocyanin-activating ***®and hidden Markov model scans of gene annotations identified a total of 714 MYB transcription factors across the genomes of four crops that span the eudicots:apple,grape,kiwifruit and *** model-based phylogenetic inference identified novel members of previously defined subgroups,and the function of specific anthocyanin-activating subgroup 6 members was assayed transiently in tobacco *** conservation within subgroup 6 highlighted one previously described and two novel short linear motifs in the disordered C-terminal *** novel motifs have a mix of hydrophobic and acidic residues and are predicted to be relatively ordered compared with flanking protein *** of motifs with the Eukaryotic Linear Motif database suggests roles in protein–protein *** of motifs and their flanking regions from strong anthocyanin activators into weak activators,and vice versa,affected *** conclude that,although the MYB C-terminal sequence diverges greatly even within MYB clades,variation within the C-terminus at and near relatively ordered regions offers opportunities for exploring MYB function and developing superior alleles for plant breeding.

关键词： phylogeny metabolism thereby

On the horizon:Hedgehog signaling to heal broken bones

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Bone Research 2022年第1期10卷 20-30页

作者： Stephanie T.Kuwahara Shuwan Liu andrew Chareunsouk Maxwell Serowoky Francesca v.Mariani University of Southern California Keck School of MedicineDepartment of Stem Cell Biology and Regenerative MedicineLos AngelesCA 90033USA

Uncovering the molecular pathways that drive skeletal repair has been an ongoing challenge. Initial efforts have relied on in vitro assays to identify the key signaling pathways that drive cartilage and bone differentiation. While these assays can provide some clues, assessing specific pathways in animal models is critical. Furthermore, definitive proof that a pathway is required for skeletal repair is best provided using genetic tests. Stimulating the Hh(Hedgehog) pathway can promote cartilage and bone differentiation in cell culture assays. In addition, the application of HH protein or various pathway agonists in vivo has a positive influence on bone healing. Until recently, however, genetic proof that the Hh pathway is involved in bone repair has been lacking. Here, we consider both in vitro and in vivo studies that examine the role of Hh in repair and discuss some of the challenges inherent in their interpretation. We also identify needed areas of study considering a new appreciation for the role of cartilage during repair, the variety of cell types that may have differing roles in repair, and the recent availability of powerful lineage tracing techniques. We are optimistic that emerging genetic tools will make it possible to precisely define when and in which cells promoting Hh signaling can best promote skeletal repair, and thus, the clinical potential for targeting the Hh pathway can be realized.

关键词： healing Hedgehog horizon

Defect detection in atomic-resolution images via unsupervised learning with translational invariance

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npj Computational Materials 2021年第1期7卷 1640-1648页

作者： Yueming Guo Sergei v.Kalinin Hui Cai Kai Xiao Sergiy Krylyuk Albert v.Davydov Qianying Guo andrew R.Lupini Center for Nanophase Materials Sciences Oak Ridge National LaboratoryOak RidgeTN 37831USA Material Measurement Laboratory National Institute of Standards and TechnologyGaithersburgMD 20899USA

Crystallographic defects can now be routinely imaged at atomic resolution with aberration-corrected scanning transmission electron microscopy(STEM)at high speed,with the potential for vast volumes of data to be acquired in relatively short times or through autonomous experiments that can continue over very long *** detection and classification of defects in the STEM images are needed in order to handle the data in an efficient ***,like many other tasks related to object detection and identification in artificial intelligence,it is challenging to detect and identify defects from STEM ***,it is difficult to deal with crystal structures that have many atoms and low *** methods used for defect detection and classification were based on supervised learning,which requires human-labeled *** this work,we develop an approach for defect detection with unsupervised machine learning based on a one-class support vector machine(OCSvM).We introduce two schemes of image segmentation and data preprocessing,both of which involve taking the Patterson function of each segment as *** demonstrate that this method can be applied to various defects,such as point and line defects in 2D materials and twin boundaries in 3D nanocrystals.

关键词： handle resolution image