166 research outputs found
Nella biblioteca di Hartmann Schedel: l'index librorum aldino del 1498 e le Decades rerum Venetarum di Marcantonio Sabellico
No full textThe contribution examines the first catalogue issued by Aldo Manuzio on 1 October 1498 and in particular the copy in the Österreichische Nationalbibliothek in Vienna (Ink. 7.A.13). A careful examination of the manuscript annotations, known to be by Hartmann Schedel, has enabled the author to identify the volume in which Schedel had the catalogue bound in his lifetime: a copy of Marcantonio Sabellico’s Decades rerum Venetarum (Venice, Andrea Torresani, 1487) also in the Österreichische Nationalbibliothek (Ink. 7.A.7). A detailed description of the item and Schedel's textual and graphic additions reveals for the first time what was one of the most significant books in the humanist's library and allow us to reconstruct the overall context of its use in the years immediately following its publication
Fungi-Induced Upper and Lower Respiratory Tract Allergic Diseases: One Entity
No full textIntroduction: Aspergillus can cause different allergic diseases including allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal rhinosinusitis (AFRS). ABPA is allergic pulmonary disease against Aspergillus antigens. AFRS is a type of chronic rhinosinusitis (CRS) presented as hypersensitivity reactions to the fungal presence in sinuses. The aim of the present study was to clarify if ABPA and AFRS could be considered as a common disease entity. Methodology: The prospective cohort study included 75 patients with ABPA. Patients were divided into two groups and compared with each other: (i) patients with CT confirmation of rhinosinusitis and presence of fungi in sinuses (ABPA+AFRS group) and (ii) patients without CT or without mycological evidence of AFRS (ABPA group). Results: Findings of this study were: (i) AFRS was confirmed in 80% of patients with ABPA; (ii) all ABPA+AFRS patients had allergic mucin while fungal hyphae were present in 60% sinonasal aspirate; (iii) ABPA+AFRS patients had more often complicated CRS with (nasal polyps) NP (p < 0.001) and more severe forms of CRS; (iv) culture of sinonasal aspirate revealed fungal presence in 97% patients with ABPA+AFRS; (v) patients with ABPA+AFRS had more common positive skin prick test (SPT) for A. fumigatus (p = 0.037), while patients without AFRS had more common positive SPT for Alternaria alternata and Penicillium notatum (p = 0.04 and p = 0.03, respectively); (vi) 67% of ABPA patients had Aspergillus induced AFRS; (vii) larger number of fungi was isolated from the air-samples obtained from homes of patients with ABPA+AFRS than from the homes of patients without AFRS, while the most predominant species were A. fumigatus and A. niger isolated from almost 50% of the air-samples. Conclusion: The pathogenesis of ABPA and AFRS is similar, and AFRS can be considered as the upper airway counterpart of ABPA. Fungi-induced upper and lower respiratory tract allergic diseases present common entity. Next studies should clarify the mechanism by which fungi turn from "normal flora" into trigger of immunological reactions, resulting in ABPA or AFRS as well as to find new approaches for its' diagnosis and treatment
An autophagy-driven pathway of ATP secretion supports the aggressive phenotype of BRAF(V600E) inhibitor-resistant metastatic melanoma cells
No full textThe ingrained capacity of melanoma cells to rapidly evolve toward an aggressive phenotype is manifested by their increased ability to develop drug-resistance, evident in the case of vemurafenib, a therapeutic-agent targeting BRAF(V600E). Previous studies indicated a tight correlation between heightened melanoma-associated macroautophagy/autophagy and acquired Vemurafenib resistance. However, how this vesicular trafficking pathway supports Vemurafenib resistance remains unclear. Here, using isogenic human and murine melanoma cell lines of Vemurafenib-resistant and patient-derived melanoma cells with primary resistance to the BRAF(V600E) inhibitor, we found that the enhanced migration and invasion of the resistant melanoma cells correlated with an enhanced autophagic capacity and autophagosome-mediated secretion of ATP. Extracellular ATP (eATP) was instrumental for the invasive phenotype and the expansion of a subset of Vemurafenib-resistant melanoma cells. Compromising the heightened autophagy in these BRAF(V600E) inhibitor-resistant melanoma cells through the knockdown of different autophagy genes (ATG5, ATG7, ULK1), reduced their invasive and eATP-secreting capacity. Furthermore, eATP promoted the aggressive nature of the BRAF(V600E) inhibitor-resistant melanoma cells by signaling through the purinergic receptor P2RX7. This autophagy-propelled eATP-dependent autocrine-paracrine pathway supported the maintenance and expansion of a drug-resistant melanoma phenotype. In conclusion, we have identified an autophagy-driven response that relies on the secretion of ATP to drive P2RX7-based migration and expansion of the Vemurafenib-resistant phenotype. This emphasizes the potential of targeting autophagy in the treatment and management of metastatic melanoma.sponsorship: Research was supported by C16/15/073 grant of the KU Leuven to P.A. and P.V., FWO grant G070115N and Stichting tegen Kanker F/2014/222 to P.A. Melanoma research in PA laboratory is supported by the MEL-PLEX ITN-consortium supported by the H2020 Marie Curie Actions. Aleksandra Dudek-Peric was supported by a fellowship of the Vlaamse Liga tegen Kanker (VLK). Abhishek D. Garg is supported by the FWO Postdoctoral (Renewal) Fellowship. This paper represents research results of the IAP7/32 funded by the Interuniversity Attraction Poles Programme, initiated by the Belgian State, Science Policy Office. We would like to thank Kristine Rillaerts and the flow cytometry core facility (KU Leuven) for technical support. We acknowledge the use, help and support of the Cell imaging Core (CIC, Prof. Pieter Vanden Berghe, KU Leuven) for their help and support within this project. (KU Leuven|C16/15/073, FWO|G070115N, Stichting tegen Kanker|F/2014/222, MEL-PLEX ITN-consortium, H Marie Curie Actions. Aleksandra Dudek-Peric, Vlaamse Liga tegen Kanker (VLK), FWO Postdoctoral (Renewal) Fellowship, Interuniversity Attraction Poles Programme, Belgian State, Science Policy Office)status: Publishe
Kulturkonflikte bei einer jungen Frau
No full textIm Rahmen eines psychoanalytisch-pädagogischen Praktikums auf der Forschungseinheit für Psychoanalytische Pädagogik des Instituts für Bildungswissenschaft der Universität Wien wurde eine junge Migrantin, die aus ihrer Heimat infolge von Krieg fliehen musste, über zwei Jahre lang von Studentinnen begleitet. Das Vorhaben meiner Diplomarbeit entwickelte sich aus dieser Art der Flüchtlingsarbeit. Der Fokus dieser Hochschulschrift richtet sich darauf, in welcher Weise sich die psychoanalytisch-pädagogisch orientierte Flüchtlingsarbeit auf die Linderung respektive Verschärfung der Kulturkonflikte der jungen Frau Milana infolge von Identifikationsprozessen mit den Studentinnen auswirkte
Thymus syriacus Essential Oil Extract: Potential Antileishmanial Activity Induced by an Apoptotic-like Death
No full textBackground: Chemotherapy continues to be the cornerstone for the management of leishmaniasis. The preferred medications are pricey and have a number of unfavorable side effects. These restrictions make it necessary to produce novel antileishmanial chemicals, and plants have opportunities in this respect. Objectives: This study aimed to evaluate the antileishmanial properties of Thymus syriacus essential oil and its mechanisms of action. Results: Our findings demonstrated that Thymus syriacus essential oil, rich in thymol, exhibited potent antileishmanial activity, with an IC50 value of approximately 1 µg/mL against L. tropica promastigotes. Furthermore, the cell cycle arrest at the sub-G0-G1 phase supported the theory that the leishmanicidal effect was mediated by apoptosis. Methods: The essential oil was characterized using gas chromatography–tandem mass spectrometry. Antileishmanial activity against L. tropica promastigotes was assessed, with mechanisms confirmed via flow cytometry. Conclusions: These results confirm the potential of Thymus syriacus essential oil as a promising therapeutic candidate for the treatment of leishmaniasis
Abstract CT137: Standard therapy versus active surveillance for low grade DCIS: the LORD trial
No full textAbstract
The introduction of population-based breast cancer screening and implementation of digital mammography have led to an increased incidence of ductal carcinoma in situ (DCIS) without a decrease in the incidence of advanced breast cancer. This suggests DCIS overdiagnosis exists.
We hypothesize that asymptomatic, low-grade DCIS can safely be managed by active surveillance. If progression to invasive breast cancer would still occur, this will be low-grade and hormone receptor positive with excellent survival rates. Also, breast-conserving treatment will still be an option, if no prior radiotherapy has been applied. It also may save many low-grade DCIS patients from intensive treatment.
We will compare active surveillance with conventional treatment, being either wide local excision (WLE) only, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy for primary low-grade DCIS, detected by calcifications only, in a phase III, open-label, non-inferiority, multi-center, randomized clinical trial legally supported by the Breast Cancer Group of the European Organisation for the Research and Treatment of Cancer (EORTC-1401-BCG). The Dutch Centers are coordinated by the BOOG Study Center (BOOG 2014-04).
Randomization will be 1:1 in to one of the following arms: active surveillance or standard treatment per local policy. In total, 1240 women (≥ 45 years) with asymptomatic, pure, low-grade DCIS, based on vacuum-assisted biopsies of calcifications as detected by population-based or opportunistic screening, without prior breast cancer, will be included. Assuming 25% of randomized women qualified to enroll in the study will drop out or will be excluded from per protocol population, at least 1,240 women need to be randomized to obtain the 930 patients required for the evaluation of the primary endpoint. The same follow-up scheme will be applied in both study arms, i.e. annual mammography for a period of 10 years. The primary end-point is ipsilateral invasive breast tumor-free rate at 10 years. Secondary end-points are among others: overall survival, breast cancer-specific survival, mastectomy rate and patient reported outcomes. Accrual has started in January 2017.
Acknowledgements: This trial is funded by Pink Ribbon Netherlands, the Dutch Cancer Society and Dutch Cancer Society/Alpe d’HuZes.
Citation Format: Jelle Wesseling, Frederieke van Duijnhoven, Konstantinos Tryfonidis, Aleksandra Peric, Elise van Leeuwen-Stok, Nina Bijker, Lotte Elshof, Emiel Rutgers. Standard therapy versus active surveillance for low grade DCIS: the LORD trial [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 CT137. doi:10.1158/1538-7445.AM2017-CT137</jats:p
STUDY OF THE ELECTRONIC GROUND STATE OF BY LASER EXCITED FLUORESCENCE FOURIER TRANSFORM SPECTROSCOPY
No full text C. Jungen, K-E.J. Hallin and A.J.Merer, Molec. Phys., 40, 25 (1980). G. Duxbury and R.N. Dixon, Molec. Phys., 43, 255 (1981). M. Peric, S.D. Peyerimhoff and R.J. Buenker, Molec.Phys. 49, 379 (1983).Author Institution: Herzberg Institute of Astrophysics, National Research Council of CanadaA large number of spin-rovibronic levels of the upper electronic state of have been excited with a single mode rhodamine 6G dye laser. Fluorescence spectra were obtained over a wide spectral range (12000-3700 cm-1) using a Fourier transform spectrometer. Levels of the bending vibration were observed from up to 10, showing the reordering of the K-structure at the barrier to linearity: their observed energies are in good agreement with the predictions of Jungen, Hallin and Merer1 , Duxbury and and Peric, Peyerimhoff and . Numerous vibrational levels involving and were also detected and approximate anharmonic parameters have been deduced
De effecten van klinisch toepasbare chemotherapeutica op deimmunogeniciteit van melanoom celdood.
No full textDuring carcinogenesis, cancer cells that are efficiently recognised by the immune system are removed, while the variants capable of evading host defence systems form an aggressive tumour. Currently, it is becoming widely accepted that an effective anticancer therapy should reverse the immunoevasive and immunosuppressive effects elicited by the cancer cells and activate anticancer immune responses that will efficiently eliminate cancerous lesions and prevent relapses. Recently, increasing attention addressed the potential of a subtype of therapy-induced apoptotic cell death, which is associated with the activation of danger signalling pathways evoking emission of damage associated molecular patterns (DAMPs), referred to as ‘immunogenic cell death (ICD)’.
During my PhD studies I investigated the ICD-inducing potential (both in vitro and in vivo, whenever possible) of the two clinically relevant anti-melanoma therapies: melphalan and vemurafenib.
Vemurafenib is an inhibitor of BRAFV600E, a commonly mutated kinase within the MAPK pathway. This targeted agent has shown significant, but short-lasting clinical responses in patients with metastatic melanoma. In the first part of this thesis, I have demonstrated that the melanoma cell lines harbouring BRAFV600E mutation responded to vemurafenib with induction of caspase-dependent cell death and danger signalling activation. The latter one resulted in exposure of two DAMPs, ecto-CRT and ecto-HSP90, but failed to emit ATP. In contrast, vemurafenib was unable to induce these processes in two isogenic drug resistant cell lines. Trying to re-establish the danger signalling in vemurafenib-resistant cells, I showed that inhibition of MAPK pathway with MEK inhibitor, the downstream kinase activated by BRAF, re-ignited cell death and danger signalling in the these cells. The MAPK pathway-inhibition induced DAMPs were functional as only melanoma cells exposing death-induced danger signals were phagocytosed and induced DAMPs-related DC maturation. Recent research from the laboratory of Dr. Guido Kroemer and our group has highlighted that ICD-associated danger signalling is modulated by autophagy, a key adaptation mechanism stimulated during melanoma progression. Accordingly, I observed that the vemurafenib-resistant cells displayed higher basal and drug-induced autophagy, therefore autophagy abrogation was particularly efficacious in boosting cell death and danger signalling in vemurafenib-resistant cells upon blockage of MEK. Nevertheless, only autophagy inhibition was insufficient to re-establish vemurafenib-resistant cells sensitivity to this treatment.
The other investigated anti-melanoma therapeutic, Melphalan (Mel), is a (loco-)regionally applied drug. It is given to the patients with extremities localized melanoma within the Mel-based isolated limb perfusion (Mel-ILP). I have showed that in human melanoma biopsies, Mel-ILP caused a pro-inflammatory microenvironment characterized by upregulation of IL1B, IL8 and IL6, which was associated with the rapid (1 h) release of IL6 and IL1β detectable in patients’ (loco-)regional sera. Additionally, the in vitro experiments have demonstrated that Mel is a mild inducer of danger signalling that resulted in caspase-dependent, ER stress-related HSP90 exposure (out of CRT, HSP70, ATP tested). Mel’s limited capacity to induce prompt and a molecularly diverse set of DAMPs has been established to rely on Mel’s moderate ER stress-inducing abilities depending on Ca2+ release. In parallel, Mel-treated human melanoma cells elicited induction of semi-mature DCs and moderate T cell activation. Moreover, in vivo prophylactic immunization showed that Mel-treated cancer cells were able to stimulate a CD8+ T cell-dependent protective anti-tumour response, although to a lesser extent than an established inducer of ICD. Interestingly, the Mel-induced moderate “anticancer vaccination effect” was strongly potentiated through combinatorial treatment with exogenously added recombinant CRT.
In conclusion, both studies indicate that the clinically applied anti-melanoma therapeutics, Mel and vemurafenib, induce danger signalling that can be further optimize with certain combinatorial approaches. Most probably the treatments’ limited ability to stimulate danger signalling is caused by the induction of restricted ER stress and stimulation of autophagy. Thus, the results obtained within my PhD studies indicated that the vemurafenib and Mel clinical effects might be improved by combination with clinically used autophagy inhibitors or Thapsigargin-related derivatives, i.e. G-202 or by the addition of rCRT, respectively. Additionally, other immunostimulatory therapies, like IDO-inhibitors, immunocheckpoint inhibitors or anticancer vaccines, might be considered to further strengthen the moderate immunogenic properties of the investigated anti-melanoma therapeutics.status: Publishe
»Der Aufsatz […] war gar nicht so ›sexy‹ wie das Bild.«: Fotografien weiblicher Körper in der DDR-Zeitschrift "Das Magazin" in den 1950er Jahren
No full textTThe present essay features Das Magazin, a popular East German monthly magazine that appeared in the GDR for the first time in 1954. The author analyzes the photographic depiction of women in issues of the 1950s. This analysis starts with the magazine’s prominent and well-researched nude photographs, but later focuses on other images of female bodies, i.e. in photo montages, to explore the different variations in which women were depicted in Das Magazin. A close examination of the images in question, their position and contextualization within Das Magazin allows for a look beyond the pages of the printed product and sheds light on the work of the layout artists. In doing so, the author argues that its creators revived certain visual strategies that had already been cultivated by the popular press in the interwar period and which were also existent beyond the boundaries of the GDR press. Thus, the notion of GDR magazines’ production practices can be enriched by transnational and historical perspectives.The present essay features Das Magazin, a popular East German monthly magazine that appeared in the GDR for the first time in 1954. The author analyzes the photographic depiction of women in issues of the 1950s. This analysis starts with the magazine’s prominent and well-researched nude photographs, but later focuses on other images of female bodies, i.e. in photo montages, to explore the different variations in which women were depicted in Das Magazin. A close examination of the images in question, their position and contextualization within Das Magazin allows for a look beyond the pages of the printed product and sheds light on the work of the layout artists. In doing so, the author argues that its creators revived certain visual strategies that had already been cultivated by the popular press in the interwar period and which were also existent beyond the boundaries of the GDR press. Thus, the notion of GDR magazines’ production practices can be enriched by transnational and historical perspectives
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