124,810 research outputs found
Abstract 4795: Nrf2 protects against chemotherapy-induced steatohepatitis and peripheral neurotoxicity
No full textAbstract
The indiscriminating protection of either normal or cancerous cells against electrophilic stresses by nuclear factor E2-related factor 2 (Nrf2) has evoked continuous controversy over its Janus face in cancer. However, both normal and cancerous cells co-exist in cancer patients, and the outcome of therapy is determined by responses of both. Here we systemically analyzed the correlation between Nrf2 expression in normal cells and chemotherapy-associated myelosuppression, steatohepatitis and peripheral neurotoxicity, and explored the possibility to predict and prevent these adverse effects by targeting Nrf2 signaling. Firstly, the toxicities of 22 clinically-used chemotherapeutic drugs were tested in bone marrow cells, liver cells and embryonic fibroblasts derived from either Nrf2 (-/-) or wild type mice, and the toxicities of drugs with IC50 in wild type cells > 2 folds higher than their Nrf2(-/-) counterparts are considered as significantly dependent on Nrf2. The dependency of taxol-induced myelosuppression on Nrf2 was confirmed in vivo, and the mRNA level of Nrf2 in peripheral blood mononuclear cells from cancer patients was reversely correlated to taxol-associated myelosuppression. Then steatohepatitis induced by irinotecan (CPT-11) and peripheral neurotoxicity induced by oxaliplatin were further investigated. CPT-11 induced intestinal toxicity in wild type mice but no significant steatohepatitis/liver toxicity was observed; however, CPT-11 treatment in Nrf2 (-/-) mice caused severer intestinal toxicity and pronounced steatohepatitis, associated with dramatically elevated serum biomarkers, accumulation of fat in liver cells, and altered liver histology. Similar results were observed for oxaliplatin-induced hepatotoxicity. Furthermore, Nrf2 deficiency significantly exaggerated oxaliplatin-induced peripheral neurotoxicity, as indicated by Von Frey test and cold plate assay. Interestingly, CDDO-Me was found to activate Nrf2 signaling in both normal tissues and xenograft tumors, while sulforaphane selectively activated Nrf2 in liver, bone marrow and peripheral nerves but not in tumors. As expected, sulforaphane significantly alleviated CPT-11-induced intestinal toxicity and oxaliplatin-induced peripheral neurotoxicity, while did not impact the therapeutic efficacy of drugs. Taken together, our results demonstrate that the toxicities of some of chemotherapeutic drugs currently in clinic usage are significantly affected by Nrf2, therefore it is possible to personalize therapeutic regimens according to Nrf2 expression in tumors and normal tissues. Specifically, CPT-11-induced steatohepatitis and intestinal toxicity and oxaliplatin-induced peripheral neurotoxicity are significantly determined by Nrf2, and Nrf2 could be selectively targeted to prevent or treat chemotherapy-induced toxicities. The present works were supported by the NSFC (No. 81272468, 91429305 and 81372266).
Note: This abstract was not presented at the meeting.
Citation Format: Liu He, Linling Que, Wenchen Yin, Baoshan Cao, Siwang Yu. Nrf2 protects against chemotherapy-induced steatohepatitis and peripheral neurotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4795. doi:10.1158/1538-7445.AM2017-4795</jats:p
La nueva emigración española. Lo que sabemos y lo que no
No full textLa crisis económica que azota el país desde hace ya seis años no podía dejar de
tener su reflejo demográfico. La población residente en España se ha reducido
en 2013 en más de 50.000 personas. Es la primera vez que esto ocurre desde
que se disponen estadísticas comparables (Cifras de Población, INE 2013). La
inversión del ciclo migratorio tiene mucho que ver en ello. Tras el boom inmigratorio
iniciado en el año 2000 y que supuso un crecimiento medio de 720.000
habitantes en el período 2002-2008, las entradas de extranjeros se fueron ralentizando
desde 2009, a la vez que los flujos de salida se intensificaban. Dichas
salidas han sido protagonizadas por ciudadanos extranjeros, pero el número de
los españoles que se marchan del país no ha dejado de crecer desde 2008 y, en
especial, desde 2011 (Gráfico 1).
De hecho, un 48% de los españoles decían estar dispuestos a trasladarse
a vivir a otro país en el Barómetro del CIS de febrero de 2012, frente a un 30%
de los suecos o el 35% de los alemanes en encuestas similares. Y un 17% confesaba
haber pensado realmente en esa posibilidad en los últimos doce meses.
Las historias de españoles que deciden emprender el camino de la emigración
inundan reportajes periodísticos y programas televisivos desde hace meses. Y
la preocupación por la posible ‘fuga de cerebros’ y sus consecuencias a medio
y largo plazo sobre la economía y el desarrollo de nuestro país son innegables.
En este documento trataremos de poner algo de orden en las cifras, combinando
y contrastando la información que ofrecen nuestras fuentes con las procedentes
de algunos de los destinos principales de la nueva emigración española.
Situaremos la dinámica migratoria española en el contexto de los movimientos
migratorios intra-UE durante la crisis para apreciar mejor su importancia cuantitativa
y cualitativa. Además examinaremos cómo se está modificando el perfil
del emigrante español desde que empezó la crisis y si se trata de una migración
permanente o de corto plazo, en función de las cifras de retorno disponibles.Peer reviewe
QUANTUM-THEORY OF PLASMONS IN LATERAL MULTIWIRE SUPERLATTICES - INTRASUBBAND PLASMONS AND THEIR COUPLING TO INTERSUBBAND PLASMONS
No full textWe analyze intrasubband plasmons in lateral multiwire superlattices and study their coupling to intersubband plasmons. We find that the local approximation is equivalent to neglecting the umklapp contributions to the plasmon energy. While this approximation fails completely for intersubband plasmons, it is reasonable for intrasubband plasmons in the long-wavelength limit. In common with intersubband plasmons, an approximate sum rule exists for intrasubband plasmons, but unlike the case for intersubband plasmons, here it is more precise because it tends to be independent of the details of the confining potential. It is predicted that in a system with n populated subbands, we should observe experimentally only one intrasubband plasmon mode. For zero wave vector along the superlattice direction, intrasubband plasmons only couple to even-parity intersubband plasmons. The coupling of intrasubband plasmons to the dominant intersubband plasmons and other odd-parity intersubband plasmons is very weak in general. Experiments are proposed to verify the importance of Coulomb coupling between wires.Physics, Condensed MatterSCI(E)33ARTICLE97127-71354
Gender and the politics of the gaze in Bronte's Wuthering Heights
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão, Programa de Pós-Graduação em Letras/Inglês e Literatura Correspondente, Florianópolis, 2009.O objetivo deste estudo é apresentar uma análise de como a imagem de Catherine é moldada pelo olhar masculino, como ela enfrenta os três tipos de olhar - o olhar dos personagens, o olhar do leitor, e o olhar do autor - e finalmente, se o olhar masculino é interrompido. O parâmetro teórico desta análise, o conceito do olhar masculino, é teorizado por Laura Mulvey no artigo "Prazer Visual e Cinema Narrativo" (1975) o qual critica a relação entre o olhar masculino e a imagem feminina do prazer visual moldado pela sociedade patriarcal. Através da crítica de Mulvey do prazer visual generizado em filmes, que pertence ao contexto do cinema clássico de Hollywood, articulo sua teoria em relação ao romance Wuthering Heights de Emily Brontë para examinar a dinâmica do olhar masculino em relação à personagem feminina Catherine. Este estudo teve também por objetivo analisar o quanto o paradigma teórico de Mulvey produzido para cinema poderia ser aplicado especificamente em um texto literário escrito no século XIX.The objective of this thesis is to present an analysis of whether Catherine's image has been shaped by the male gaze, how she contends with the three looks of the male gaze - the look of the characters, the look of the reader, and the look of the author - and finally, how the male gaze is broken. The theoretical parameter of this analysis, the concept of the male gaze, is theorized by Laura Mulvey in the article "Visual Pleasure and Narrative Cinema" (1975) which critiques the relation between the male gaze and the female image within the patriarchal molding of visual pleasure. Borrowing Mulvey's critique of the gendering of visual pleasure in films, which pertains to the context of classical Hollywood cinema, I have articulated her theory in relation to Emily Brontë's Wuthering Heights, to examine the dynamics of the male gaze regarding the female character, Catherine. This study also aimed at examing the extent to which Mulvey's theoretical paradigm produced for cinema could be articulated specifically in relation to a literary text written in the nineteenth century
Calciumcarbonaatfabriek
No full textDocument(en) uit de collectie Chemische ProcestechnologieDelftChemTechApplied Science
Hou Renzhi, 1911-2013 Obituary
No full texthttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000330909100014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701GeographyHistory Of Social [email protected]
Carta sobre un cajoncito que contiene prendas indígenas, 1776 enero 20
No full textCarta a Junípero Serra en la que se reconoce que aún no se ha recibido un cajoncito con prendas de indígenas recién descubiertos. El autor asegura a Serra que le avisará cuando lo reciba y expresa su gratitud por la fina memoria. —— Letter to Junípero Serra acknowledging that they have not yet received a small box containing garments of newly encountered Indigenous people. The author assures Serra that they will notify them upon receipt and expresses gratitude for the thoughtful remembrance. 1 f. (2 p.
Activation of Nrf2-ARE signaling mitigates cyclophosphamide-induced myelosuppression
No full textMyelosuppression is the most common dose-limiting adverse effect of chemotherapies. In the present study, we investigated the involvement of nuclear erythroid 2-related factor 2 (Nrf2) in cyclophosphamide-induced myelosuppression in mice, and evaluated the potential of activating Nrf2 signaling as a preventive strategy. The whole blood from Nrf2(-/-) mice exhibited decreased antioxidant capacities, while the bone marrow cells, peripheral blood mononuclear cells and granulocytes from Nrf2(-/-) mice were more susceptible to acrolein-induced cytotoxicity than those from wild type mice. Single dosage of cyclophosphamide induced significantly severer acute myelosuppression in Nrf2(-/-) mice than in wild type mice. Furthermore, Nrf2(-/-) mice exhibited greater loss of peripheral blood nucleated cells and recovered slower from myelosuppression nadir upon multiple consecutive dosages of cyclophosphamide than wild type mice did. This was accompanied with decreased antioxidant and detoxifying gene expressions and impaired colony formation ability of Nrf2(-/-) bone marrow cells. More importantly, activation of Nrf2 signaling by CDDO-Me significantly alleviated cyclophosphamide-induced myelosuppression, while this alleviation was diminished in Nrf2(-/-) mice. In conclusion, the present study shows that Nrf2 plays a protective role in cyclophosphamide-induced myelosuppression and activation of Nrf2 is a promising strategy to prevent or treat chemotherapy-induced myelosuppression. (C) 2016 Elsevier Ireland Ltd. All rights reserved.National Natural Science Foundation of China [81272468, 21001011]; WU JIEPING Medical foundation [320.6750.12196]SCI(E)[email protected]; [email protected]
Exploring the Evolution of Passenger Characteristics Based on Smart Card Data: A Case Study of Shenzhen, China
No full textPassenger travel characteristics (PTCs) are characteristics that are sought from the information contained in trips, such as travel frequency, travel mode, departure location, and etc. Understanding PTCs can help develop passenger-oriented planning and service policies, so analysis of PTCs is a topic of constant interest to researchers and transportation service providers. However, PTCs vary with the change of many factors, such as network, price policy, service. The process or trend of PTCs change, which is called the evolution of PTCs, are useful for assessing the impact of external factors changes on passengers.Transport, Infrastructure and Logistic
Application of KinectTM and wireless technology for patient data recording and viewing system in the course of surgery
No full textIn modern operating room (OR) conditions, a patient\u27s computed tomography (CT) or magnetic resonance imaging (MRI) scans are some of the most important resources during surgical procedures. In practice, the surgeon is impelled to scrub out and back in every time he needs to scroll through scan images in mid-operation. To prevent leaving the operating table, many surgeons rely on assistants or nurses and give instructions to manipulate the computer for them, which can be cumbersome and frustrating. As a motivation for this study, the use of touchless (non-contact) gesture-based interface in medical practice is incorporated to have aseptic interactions with the computer systems and with the patient\u27s data. The system presented in this paper is composed of three main parts: the Trek Ai-Ball Camera, the Microsoft Kinect™, and the computer software. The incorporation of these components and the developed software allows the user to perform 13 hand gestures, which have been tested to be 100 percent accurate. Based on the results of the tests performed on the system performance, the conclusions made regarding the time efficiency of the viewing system, the quality and the safety of the recording system has gained positive feedback from consulting doctors. © 2017 Author(s)
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