8 research outputs found
A textual research of the writing of miscellaneous notes in Wanli reign of Ming dynasty = Ming Wanli bi ji cheng shu kao lun
No full textUp till now, the study of miscellaneous notes has largely focused on the
content of the texts. Nonetheless the research on their sources, writing modes,
and the note-recording process is quite inadequate. This thesis applies research
methods in communication studies and stylistics to the study of miscellaneous
notes in Wanli reign of Ming Dynasty, attempting an ontological research on
the information collection and writing process of miscellaneous notes.
The first part of the thesis explores the information sources of
miscellaneous notes, using miscellaneous notes of recorded conversation as an
example. On the basis of a solid survey of the conversationalists in the
miscellaneous notes of this period, this thesis carried out a meticulous
investigation into the lives of the key conversationalists. This part of my study
reveals that the conversationalists mainly consist of scholars, officials and
common literati. The conversationalists collected their sources from their
official experiences as well as local or family legends, and endowed their
stories with strong local characteristics. Recorded conversations include private talks within family, conversations between hosts and guests and talks in literary
circles. The diverse backgrounds of conversationalists and the different
occasions where the talks took place impact significantly on the contents, the
formats and the styles of miscellaneous notes.
The second part discusses several important issues in note-recording by
analogy and induction. The first topic concerns the motives of note-recording.
The discourse context of Wanli reign induces three major motives. The first
one, taking Confucian ideals as its lead, aspires to improve human society
through passing on wise words and noble deeds.The second one uses
miscellaneous notes instrumentally for collecting and compiling knowledge,
usually in the form of scattered and unordered items. The last one, influenced
by the literati trend of displaying distinguished talent and superior taste in the
late Ming, records proverbs and anecdotes in pursuit of a refined literary
pleasure, Moreover, the author selects the materials by evaluating their
authenticity, rarity, and relevance to the authorial concerns. Their most striking
features, as being unarranged and in disorder, are determined by such factors as
the authors’ different age levels, as well as the various materials with which
they wrote and preserved their works.
The third part delineates the process of revision and polish of
miscellaneous notes by conducting a case study on Er tan, a work widely
circulated during Wanli reign. This part carefully examines the life of the
author Wang Tonggui and goes on to explore the writing and editing process of
this work. A thorough comparison of the texts of different versions discloses
many modifications by the author as the work expanded from fifteen volumes
to fifty-four volumes. The changes include the increasing of the numbers of
tales and anecdotes under certain themes, the amplification or modification of
the original comments, as well as a re-categorization of items. All these
changes have facilitated Er Tan to develop from a work resembling oral
literature into a book with written texts expected to be read.published_or_final_versionChineseDoctoralDoctor of Philosoph
Calcium Homeostasis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Get PDFRationale: Cardiomyocytes generated from human induced pluripotent stem cells (hiPSCs) are suggested as the most promising candidate to replenish cardiomyocyte loss in regenerative medicine. Little is known about their calcium homeostasis, the key process underlying excitation-contraction coupling. Objective: We investigated the calcium handling properties of hiPSC-derived cardiomyocytes and compared with those from human embryonic stem cells (hESCs). Methods and Results: We differentiated cardiomyocytes from hiPSCs (IMR90 and KS1) and hESCs (H7 and HES3) with established protocols. Beating outgrowths from embryoid bodies were typically observed 2 weeks after induction. Cells in these outgrowths were stained positively for tropomyosin and sarcomeric alpha-actinin. Reverse-transcription polymerase chain reaction studies demonstrated the expressions of cardiac-specific markers in both hiPSC- and hESC-derived cardiomyocytes. Calcium handling properties of 20-day-old hiPSC- and hESC-derived cardiomyocytes were investigated using fluorescence confocal microscopy. Compared with hESC-derived cardiomyocytes, spontaneous calcium transients from both lines of hiPSC-derived cardiomyocytes were of significantly smaller amplitude and with slower maximal upstroke velocity. Better caffeine-induced calcium handling kinetics in hESC-CMs indicates a higher sacroplasmic recticulum calcium store. Furthermore, in contrast with hESC-derived cardiomyocytes, ryanodine did not reduce the amplitudes, maximal upstroke and decay velocity of calcium transients of hiPSC-derived cardiomyocytes. In addition, spatial inhomogeneity in temporal properties of calcium transients across the width of cardiomyocytes was more pronounced in hiPSC-derived cardiomyocytes than their hESC counterpart as revealed line-scan calcium imaging. Expressions of the key calcium-handling proteins including ryanodine recptor-2 (RyR2), sacroplasmic recticulum calcium-ATPase (SERCA), junction (Jun) and triadin (TRDN), were significantly lower in hiPSC than in hESCs. Conclusions: The results indicate the calcium handling properties of hiPSC-derived cardiomyocytes are relatively immature to hESC counterparts. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201
sFAS/sFASL and sMMP-7: New soluble markers of prognosis and response to therapy in advanced colorectal cancer
Get PDF[cat] 1 INTRODUCCIÓN El cáncer colorrectal (CCR) es la tercera causa de diagnóstico de cáncer en todo el mundo. El 11-27% de pacientes se diagnostican en estadio avanzado o metastático. De los inicialmente diagnosticados de CCR localizado, un 25-50% acabarán presentando metástasis. En los últimos años hemos asistido a un leve decremento de la incidencia y de la mortalidad por CCR, probablemente debido a la mejora en los programas de ¨screening¨ y a las mejoras en las estrategias terapéuticas. El CCRM tiene un pronóstico pésimo. La supervivencia global se sitúa entre los 5-6 meses, en pacientes que no reciben tratamiento. En los últimos años, la implementación de las nuevas terapias ha elevado esta media hasta los 15-18 meses. En la actualidad, ¿existe alguna manera para reconocer con que tipo de CCRM estamos tratando? ¿Cómo podemos determinar de antemano como se comportará el CCRM, en términos de pronóstico y respuesta a los tratamientos? Hasta la fecha se han realizado multitud de estudios con la intención de determinar factores pronósticos y predictivos de respuesta en CCRM. En el texto se recogen detalladamente los más importantes. Sin embargo, existen diferentes factores que explican que estos factores no se hayan implementado en la práctica clínica habitual. Entre ellos está la falta de estudios clínicos prospectivos confirmativos y, por otra parte está la heterogeneidad que impera a la hora de realizar los estudios sobre marcadores. Para solventar este último punto, el Nacional Cancer Institute ha creado unas guías a seguir (REMARK). Actualmente hace falta diseñar convenientemente estudios prospectivos confirmativos. En el Hospital Clínic de Barcelona hemos desarrollado (2001) un algoritmo terapéutico basado en el patrón de metástasis al debut de la enfermedad y los algunos de los factores más utilizados como pronósticos. 2 HIPÓTESIS Y OBJETIVOS: En nuestra hipótesis, hemos seleccionado dos determinantes moleculares (MMP-7 y sFAS/sFASL) como potenciales marcadores pro'osticos y predictivos de respuesta a terapia en CCRM. Matrilisina o metaloproteasa-7 (MMP-7) es una enzima proteolítica perteneciente a la familia de las metaloproteasas. Es sintetizada y secretada al medio por células tumorales. Detalles sobre la regulación de su expresión y función pueden hallarse en el texto original. Entre sus actividades destacamos su capacidad de cortar la proteína de membrana FASL. El receptor FAS y su ligando FASL son receptores transmebrana. Su interacción induce la activación de la vía extrínseca de apoptosis. Existen fracciones solubles de estas proteínas: sFAS y sFASL. sFAS es resultante de fenómenos de "splicing" alternativo. Su función es predominantemente proapoptótica. sFASL resulta de cortar la proteína de membrana, a cargo de proteasas como MMP-7. La función de sFASL es básicamente antiapoptótica. Las fracciones solubles pueden anularse entre sí. Su función final depende de los balances entre ellas, por lo que el ratio pude ser un estimador de la función apoptótica final. FAS y FASL son proteínas que se han relacionado con la respuesta apoptótica al tratamiento quimioterápico. El CCRM muestra un patrón de resistencia a la inducción de apoptosis vía FAS-FASL. El papel de las formas solubles sFAS y sFASL en quimioresistencia nunca ha sido evaluado. MMP-7 se ha relacionado con un fenotipo agresivo de CCRM, aunque también con quimioresistencia, debido a su capacidad de corte de FASL. Los niveles séricos de sFAS han demostrado estar aumentados en pacientes con CCRM. La medición de los niveles séricos de sFASL y MMP-7 nunca se ha llevado a cabo en pacientes con CCRM.Nuestra hipótesis es que los niveles séricos de MMP-7, sFAS y sFASL en pacientes con CCRM puden ser marcadores biológicos que estimen la agresividad y la quimioresistencia. A modo de concepto nuevo y, teniendo en cuenta que el tumor varía en el tiempo, está el hecho que los marcadores biológicos deberían poderse obtener no solo en el momento del diagnóstico sino en cualquier momento durante la evolución de la enfermedad. Si esto fuera así, el método de obtención debería ser fácil y no invasivo. Los niveles séricos de MMP-7, sFAS y sFASL y sus variaciones durante el tiempo deberían ser predictores de quimioresistencia en CCRM en cualquier momento durante la enfermedad.Los objetivos se pueden resumir en:A) Determinar si los niveles séricos basales de MMP-7 en pacientes con CCRM y establecer su valor pronóstico. B) Determinar los niveles séricos de sFAS y sFASL en pacientes con CCRM, antes y durante el tratamiento quimioterápico, y establecer una correlación con la respuesta tumoral, de manera que podamos valorar su papel como marcador predictivo de respuesta. C) En función de los resultados obtenidos, diseñar estudios clínicos prospectivos para validar el valor de los niveles séricos de MMP-7 y sFAS/sFASL como nuevos marcadores solubles de pronóstico y respuesta al tratamiento en CCRM. 3. RESULTADOS: Los resultados han sido hechos públicos en dos artículos, uno de ellos aparecido en 2005 y otro de ellos en prensa. Ambos se recogen en la tesis. 4. CONCLUSIONES: En resumen, concluimos que:-MMP-7 puede medirse en el suero y sus niveles basales son un factor pronóstico independiente en pacientes con CCRM.-Las variaciones de los niveles séricos de sFAS/FASL en pacientes con CCRM en tratamiento quimioterápico correlacionan con la respuesta tumoral.-La detección de un descenso del los valores séricos del ratio sFAS/sFASL, habitualmente debido al incremento de sFASL, se relaciona con quimioresistencia.-Los valores séricos del ratio sFAS/sFASL podrían utilizarse como un predictor dinámico de respuesta al tratamiento quimioterápico en pacientes con CCRM y su valor debería validarse en estudios clínicos prospectivos. -Nuestras observaciones, en los campos básico y clínico, indican que MMP-7 estaría implicada en quimioresistencia primaria o intrínseca y adquirida, en CCRM.-Una hipótesis generada "de novo" es que un patrón sérico consistente en niveles altos de MMP-7 y de FASL, tanto si se detecta antes de iniciar el tratamiento como durante éste, implicaría qumioresistencia y, en consecuencia, mal pronóstico. -MMP-7 y sFAS/sFASL, los nuevos marcadores solubles que proponemos, se pueden detector fácilmente a través de una técnica no invasiva.-MMP-7 y sFAS/sFASL, los nuevos marcadores solubles propuestos, se pueden detectar en cualquier momento a lo largo de la enfermedad y refleja la biología tumoral cambiante, de una manera dinámica. -De acuerdo a los resultados presentados y las hipótesis generadas a partir de éstos, hemos diseñado estudios clínicos prospectivos para determinar la relevancia clínica de los niveles séricos de MMP-7 y sFAS/sFASL, como nuevos marcadores solubles de quimioresistencia en CCRM
Pancreatico-biliary endoscopic ultrasound: A systematic review of the levels of evidence, performance and outcomes
No full textOur aim was to record pancreaticobiliary endoscopic ultrasound (EUS) literature of the past 3 decades and evaluate its role based on a critical appraisal of published studies according to levels of evidence (LE). Original research articles (randomized controlled trials, prospective and retrospective studies), meta-analyses, reviews and surveys pertinent to gastrointestinal EUS were included. All articles published until September 2011 were retrieved from PubMed and classified according to specific disease entities, anatomical subdivisions and therapeutic applications of EUS. The North of England evidencebased guidelines were used to determine LE. A total of 1089 pertinent articles were reviewed. Published research focused primarily on solid pancreatic neoplasms, followed by disorders of the extrahepatic biliary tree, pancreatic cystic lesions, therapeutic-interventional EUS, chronic and acute pancreatitis. A uniform observation in all six categories of articles was the predominance of LE III studies followed by LE IV, IIb, IIa, Ib and I a, in descending order. EUS remains the most accurate method for detecting small ( 3 cm) pancreatic tumors, ampullary neoplasms and small ( 4 mm) bile duct stones, and the best test to define vascular invasion in pancreatic and peri-ampullary neoplasms. Detailed EUS imaging, along with biochemical and molecular cyst fluid analysis, improve the differentiation of pancreatic cysts and help predict their malignant potential. Early diagnosis of chronic pancreatitis appears feasible and reliable. Novel imaging techniques (contrast-enhanced EUS, elastography) seem promising for the evaluation of pancreatic cancer and autoimmune pancreatitis. Therapeutic applications currently involve pancreaticobiliary drainage and targeted fine needle injection-guided antitumor therapy. Despite the ongoing development of extra-corporeal imaging modalities, such as computed tomography, magnetic resonance imaging, and positron emission tomography, EUS still holds a leading role in the investigation of the pancreaticobiliary area. 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GWTC-3: Compact Binary Coalescences Observed by LIGO and Virgo During the Second Part of the Third Observing Run
Get PDFThe third Gravitational-Wave Transient Catalog (GWTC-3) describes signals
detected with Advanced LIGO and Advanced Virgo up to the end of their third
observing run. Updating the previous GWTC-2.1, we present candidate
gravitational waves from compact binary coalescences during the second half of
the third observing run (O3b) between 1 November 2019, 15:00 UTC and 27 March
2020, 17:00 UTC. There are 35 compact binary coalescence candidates identified
by at least one of our search algorithms with a probability of astrophysical
origin . Of these, 18 were previously reported as
low-latency public alerts, and 17 are reported here for the first time. Based
upon estimates for the component masses, our O3b candidates with
are consistent with gravitational-wave signals from
binary black holes or neutron star-black hole binaries, and we identify none
from binary neutron stars. However, from the gravitational-wave data alone, we
are not able to measure matter effects that distinguish whether the binary
components are neutron stars or black holes. The range of inferred component
masses is similar to that found with previous catalogs, but the O3b candidates
include the first confident observations of neutron star-black hole binaries.
Including the 35 candidates from O3b in addition to those from GWTC-2.1, GWTC-3
contains 90 candidates found by our analysis with
across the first three observing runs. These observations of compact binary
coalescences present an unprecedented view of the properties of black holes and
neutron stars.Comment: 88 pages (10 pages author list, 31 pages main text, 1 page
acknowledgements, 24 pages appendices, 22 pages bibliography), 17 figures, 16
tables. Update to match version to be published in Physical Review X. Data
products available from https://gwosc.org/GWTC-3
Depression: Can we predict who will relapse?
No full textThis thesis addresses risk factors and proposed mechanisms to explain relapse to depression. Volume 1 comprises three parts: Part 1 is a literature review consisting of meta-reviews of systematic and non-systematic reviews of studies reporting on risk factors for relapse to depression, and a systematic-review of neuroimaging and experimental studies investigating risk factors for relapse and potential mechanisms of action of these risk factors. The reviews found that only residual symptoms of depression at the end of treatment and childhood maltreatment were sufficiently evidenced as predictors of relapse and neither have great clinical utility. A number of psychological and neuropsychological factors were suggested to play a role in conferring risk for relapse. Considering the inter-relationships between these factors the reviews were used to propose a conceptual framework which may be used to help guide future research into relapse to depression in adults. Part 2 is an empirical paper in which data were analysed from service users of a primary care mental health service to identify risk factors for relapse and for the presence of residual symptoms, and survival analysis methods were used to determine when relapses occur most often and what factors impact survival. In addition, a prospective cohort study was formed to investigate the relationship between cognitive control and depressive symptoms. The findings confirmed that cognitive control can be used to predict residual symptoms of depression post-treatment and therefore potentially to predict relapse. Part 3 is a critical appraisal focussing on the theoretical reasons as to why studying relapse in a manner as used in the prospective study is so important and discusses the logistical difficulties conducting such research in the current context of NHS services and of the D.Clin.Psy research project. Methodological decisions made that impacted upon the research process are discussed and reflective conclusions are offered
AI is a viable alternative to high throughput screening: a 318-target study
Get PDF: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Proceedings of The HKIE Geotechnical Division 43rd Annual Seminar: Towards a Smart-Green-Resilient Geo-Future for World-class City
Get PDFThis seminar proceedings contain articles on the various research ideas of the academic community and practitioners presented at The HKIE Geotechnical Division 43rd Annual Seminar (GDAS2023). This seminarprovides a platform for policymakers, practitioners, and academia to share their insights and brainstorm ideas with a view to seizing future opportunities and shaping the new future of Hong Kong. GDAS2023 was organized by the Geotechnical Division, The Hong Kong Institution of Engineers on 19th May 2023.
Seminar Title: The HKIE Geotechnical Division 43rd Annual SeminarSeminar Acronym: GDAS2023Seminar Date: 19 May 2023Seminar Location: Hong KongSeminar Organizers: Geotechnical Division, The Hong Kong Institution of Engineers
Link to the GDAS2021 Proceedings: Proceedings of The HKIE Geotechnical Division 41st Annual Seminar
Link to the GDAS2022 Proceedings: Proceedings of The HKIE Geotechnical Division 42nd Annual Semina
