Public Health and the Politics of Haussmannization in Nineteenth-Century Paris, 1830-1870

Throughout the Second Empire, Napoléon III and his Prefect of the Seine, Georges Haussmann, engaged in a series of urban reform projects that transformed Paris. These projects, often collectively referred to as Haussmannization, entailed the construction of boulevards, expansion of the sewer system, and clearance of what the state considered insalubrious housing. This term was largely prescribed to worker-class housing and used as a medical justification to target and destroy working-class communities. However, as this paper discusses, the understanding of insalubrity was shaped by hygienists\u27 pathologization of poverty, crime, and working-class militancy in response to the arrival of cholera and the increase in working-class unrest during the July Monarchy. Hygienists hypothesized that these issues stemmed from workers\u27 moral degeneration and constituted public health crises due to their allegedly contagious nature. In framing these issues as public health crises, hygienists advocated for state intervention to regulate these workers. Leveraging hygienists\u27 rhetoric, Napoléon III justified his destruction of working-class communities as a measure to improve public health while decreasing workers’ potential social and political power. This thesis adds to current literature that suggests Haussmannization aimed to consolidate control over workers by eradicating working-class spaces and elaborates on public health’s role in legitimizing Napoléon III’s marginalization of workers

Assessing the impacts of global change on water quantity and quality: Large-scale modelling studies for Central Asia

Water resources in the semi-arid to arid areas of Central Asia are often limited by low precipitation, and hence vulnerable to impacts of global change, i.e. socio-economic development and climate change. Both, socio-economic development and climate change are very likely causing significant changes as water resources are affected by two main effects: Firstly, growing population and industrial activities in the region raise the pressure on water resources due to increasing water abstractions. Secondly, air temperature in the region has been rising in the past far above global average and it is expected to increase further, which will lead to changes in runoff generation and therefore water availability. Increasing temperature as well as increasing water abstractions will affect water quantity and consequently water quality as a result of higher pollution intake or reduction in dilution capacity. Thus, it is of crucial importance to analyse and assess the state of current and future water resources to implement sustainable water management as the above mentioned effects very likely causing significant changes of water resources. Within the last years, the number of scientific research studies using large-scale models to simulate water availability and water use has increased substantially. Several new datasets from earth observations and new or improved models have been published (Werth et al. 2009; Werth and Güntner 2010; van Beek et al. 2011). Nevertheless, those studies focussed on water quantity and did not take into account impacts on water quality induced by global change although changes in water quality affecting aquatic ecosystems and species. Furthermore, spatially explicit large-scale modelling studies have not been carried out for Mongolia and Central Asia to get a comprehensive overview and assessment. To address this research gap, the large-scale water resource modelling framework WaterGAP 3 was applied to Central Asia with a focus on Mongolia to simulate impacts on current and future water resources. WaterGAP 3 consists of hydrology, water use and water quality sub-models in order to simulate current and future water quantity and quality

Charakterisierung neuer Interaktionspartner der NFAT-vermittelten Transkription im Pankreaskarzinom

Die nukleären Faktoren aktivierter T-Zellen (NFATs) wurden vor allem in der Regulierung der Immunantwort charakterisiert, wo sie in der Induktion der Genübertragung als Transkriptionsfaktoren eine entscheidende Rolle spielen (Rao et al. 1997). In den letzten Jahren wurden NFAT-Proteine nicht nur in T-Zellen, sondern auch in anderen Zellen außerhalb des Immunsystems beobachtet, wo sie die Expression zentraler Gene der Differenzierung und des Wachstums kontrollieren (Viola et al. 2004). So werden sie u.a. auch in Pankreaskarzinomzellen (Buchholz et al. 2006) exprimiert. NFAT-Proteine sind primär zytoplasmatisch lokalisiert und translozieren erst nach Aktivierung in den Zellkern. Dort interagieren sie mit anderen Bindungspartnern an der DNA (Hogan et al. 2003). Es handelt sich hierbei um Transkriptionsfaktoren, die mit NFAT-Proteinen kooperieren und so die Selektion und Regulierung NFAT-kontrollierter Gene beeinflussen. Die vorliegende Arbeit fokussiert auf NFATc2, welches zwar eine hohe Expressionsintensität im Pankreaskarzinom aufweist, dessen Funktion und DNA-regulierenden Eigenschaften hier jedoch unbekannt sind. Ziel der vorliegenden Arbeit ist es, mögliche Interaktions-partner des Transkriptionsfaktors NFATc2 in Pankreaskarzinomzellen zu identifizieren und zu kennzeichnen. Zunächst wird in Vorarbeiten die Expression von NFATc2 und potentieller Partnerproteine, die bereits in der Literatur in anderen Zellarten und Geweben beschrieben werden und zusätzlich die Kriterien einer Calcium-abhängigen Regulierung und einer nachgewiesenen onkogenen Wirkung im Organismus erfüllen, in einer Reihe etablierter Pankreaskarzinomzelllinien untersucht und bestätigt. Ebenso wird Ionomycin, ein Stimulans, gewählt, um eine zuverlässige Translokation von NFATc2 in den Zellkern durch Aktivierung des Calcium-Calcineurin-Signalwegs zu garantieren. Nachteil dieses Stimulus ist seine Zelltoxizität, die eine Verwendung für Langzeitexperimente ausschließt. Die Wirkungsweise von Ionomycin wird durch die Immunfluoreszenzstudie, sowie auf Proteinebene durch Western Blot dargelegt. In ersten Interaktionsversuchen mittels Immunpräzipitation zeigt sich eine Bindung von NFATc2 mit dem Transkriptionsfaktor Sp1. Zur Verifizierung und Charakterisierung der hier beschriebenen Interaktion zwischen NFATc2 und Sp1 bezüglich des Zeitintervalls werden weitere Methoden angewandt. In der Immunfluoreszenzstudie ist eine Kolokalisation der onkogenen Transkriptions-faktoren Sp1 und NFATc2 in Pankreaskarzinomzellen unter Ionomycin-stimulation zu erkennen. Weiterführend wird gezeigt, dass die Transkriptions-faktoren im selben Immunkomplex an der NFAT-Targetsequenz GGAAA in direkte Wechselwirkung treten und Sp1 die funktionelle Aktivität seines Bindungspartners an dem NFAT-responsiven Promotorkonstrukt steigert. Diese Interaktion wird durch Ionomycin in der frühen Phase der Stimulation (bis 60 min) begünstigt. Im zweiten Teil der Arbeit wird die physikalische Interaktion von NFATc2 und Sp1 anhand von Sp1-Deletionsmutanten näher charakterisiert. Dabei kann sowohl auf physikalischer Ebene, mittels Immunpräzipitation, als auch auf funktionaler Ebene mittels Luziferase-Assay gezeigt werden, dass der N-Terminus von Sp1 mit dem Transkriptionsfaktor NFATc2 interagiert und beide Faktoren gemeinsam die Funktion ihrer Zielgene regulieren. Mittels Expressionsprofilanalyse werden im dritten Teil dieser Arbeit einige interessante Zielgene von NFATc2 und Sp1, die nach Ionomycinbehandlung differentiell exprimiert werden, identifiziert. Darunter finden sich das Proto-onkogen c-Fos, der Tumornekrosefaktor TNF-alpha sowie das Adhäsions-molekül Integrin-β-3. Wird Sp1 durch siRNA-Technologie gehemmt, findet sich bei c-Fos und TNF-alpha ein abgeschwächter Ionomycineffekt, sodass die DNA-Bindungsaktivität von Sp1-artigen Transkriptionsfaktoren für die NFATc2-vermittelte Regulation dieser Gene von Bedeutung sein muss. Diese Beobachtung wird in unabhängigen Untersuchungen stellvertretend für c-Fos durch qRT-PCR und dessen funktionelle Bedeutung für die Pankreas-karzinomzelle mittels Thymidin-Proliferations-Assay dargelegt. Als Ergebnis kann eine verminderte Zellproliferation, sowohl nach 24 h als auch nach 48 h bei Knockdown von beiden Transkriptionsfaktoren, beobachtet werden. Schlussfolgernd besteht die Vermutung, dass die Bindungspartner NFATc2 und Sp1 im Pankreaskarzinom interagieren und gemeinsam Zielgene, die für das Zellwachstum verantwortlich sind, regulieren. Der Verlust bereits eines Transkriptionsfaktors verhindert die onkogene Komplexbildung und die Expression möglicher zellzyklusregulierender Gene

The active role of the transcription factor Sp1 in NFATc2-mediated gene regulation in pancreatic cancer

BackgroundAdenocarcinoma of the pancreas is one of the most aggressive tumor diseases affecting the human body. The oncogenic potential of pancreatic cancer is mainly characterized by extremely rapid growth triggered by the activation of oncogenic signaling cascades, which suggests a change in the regulation of important transcription factors. Amongst others, NFAT transcription factors are assumed to play a central role in the carcinogenesis of pancreatic cancer. Recent research has shown the importance of the transcription factor Sp1 in the transcriptional activity of NFATc2 in pancreatic cancer. However, the role of the interaction between these two binding partners remains unclear. The current study investigated the role of Sp1 proteins in the expression of NFATc2 target genes and identified new target genes and their function in cells. A further objective was the domain of the Sp1 protein that mediates interaction with NFATc2.The involvement of Sp1 proteins in NFATc2 target genes was shown by means of a gene expression profile analysis, and the results were confirmed by quantitative RT-PCR. The functional impact of this interaction was shown in a thymidine incorporation assay. A second objective was the physical interaction between NFATc2 and different Sp1 deletion mutants that was investigated by means of immunoprecipitation.ResultsIn pancreatic cancer, the proto-oncogene c-Fos, the tumor necrosis factor TNF-alpha, and the adhesion molecule integrin beta-3 are target genes of the interaction between Sp1 and NFATc2. Loss of just one transcription factor inhibits oncogenic complex formation and expression of cell cycle-regulating genes, thus verifiably decreasing the carcinogenic effect. The current study also showed the interaction between the transcription factor NFATc2 and the N-terminal domain of Sp1 in pancreatic cancer cells. Sp1 increases the activity of NFATc2 in the NFAT-responsive promoter.ConclusionsThe regulation of gene promotors during transcription is a rather complex process because of the involvement of many proteins that - as transcription factors or co-factors - regulate promotor activity as required and control cell function. NFATc2 and Sp1 seem to play a key role in the progression of pancreatic cancer

PENINGKATAN VISIBILITAS DAN PROMOSI DIGITAL KAMPUNG ADAT KURANJI

Kuranji Traditional Village has the potential to become a cultural tourism object that can represent and introduce Minangkabau culture well at the national and international levels. Even so, Kuranji Traditional Village is still constrained by several crucial issues such as infrastructure, amenities and ancillary services, human resources, promotion (visibility in cyberspace), and strategic development plans. The purpose of this activity is to increase the visibility and digital promotion of the Kuranji Traditional Village in cyberspace. This activity was carried out using the workshop method; first, participants are given materials and directions; second, participants work on or practice the material that has been delivered; the three presenters and participants held discussions to resolve situational problems that were not covered in the material previously presented. The results of the activity showed positive things where managers and cultural activists in the Kuranji Traditional Village for development felt that this activity was very useful for improving the Kuranji Traditional Village as a cultural tourism object as well as an effort to increase the financial strength of the Kuranji Traditional Village community to achieve its main goal, maintenance of Minangkabau culture, through this digital promotion. Keywords: Visibility, Digital promotion, Kampung Adat Kuranj

Both coiling and clipping induce the time-dependent release of endogenous neuropeptide Y into serum

BackgroundThe vaso- and psychoactive endogenous Neuropeptide Y (NPY) has repeatedly been shown to be excessively released after subarachnoid hemorrhage and in numerous psychiatric disorders. NPY is stored in sympathetic perivascular nerve fibers around the major cerebral arteries. This prospective study was designed to analyze the impact of microsurgical and endovascular manipulation of the cerebral vasculature versus cranio- and durotomy alone on the serum levels of NPY.Methods58 patients (drop-out n = 3; m:f = 26:29; mean age 52.0 ± 14.1 years) were prospectively enrolled. The vascular group underwent repair for unruptured intracranial aneurysms (UIA) of the anterior circulation [endovascular aneurysm occlusion (EV) n = 13; microsurgical clipping (MS) n = 17]; in the non-vascular group, 14 patients received microsurgical resection of a small-sized convexity meningioma (CM), and 11 patients with surgically treated degenerative lumbar spine disease (LD) served as control. Plasma was drawn (1) before treatment (t0), (2) periprocedurally (t1), (3) 6 h postprocedurally (t2), (4) 72 h postprocedurally (t3), and (5) at the 6-week follow-up (FU; t4) to determine the NPY levels via competitive enzyme immunoassay in duplicate serum samples. We statistically evaluated differences between groups by calculating one-way ANOVA and for changes along the time points using repeated measure ANOVA.ResultsExcept for time point t0, the serum concentrations of NPY ranged significantly higher in the vascular than in the non-vascular group (p < 0.001), with a slight decrease in both vascular subgroups 6 h postprocedurally, followed by a gradual increase above baseline levels until FU. At t3, the EV subgroup showed significantly higher NPY levels (mean ± standard deviation) than the MS subgroup (0.569 ± 0.198 ng/mL vs. 0.415 ± 0.192 ng/mL, p = 0.0217). The highest NPY concentrations were measured in the EV subgroup at t1, t3, and t4, reaching a climax at FU (0.551 ± 0.304 ng/mL).ConclusionOur study reveals a first insight into the short-term dynamics of the serum levels of endogenous NPY in neurosurgical and endovascular procedures, respectively: Direct manipulation within but also next to the major cerebral arteries induces an excessive release of NPY into the serum. Our findings raise the interesting question of the potential capacity of NPY in modulating the psycho-behavioral outcome of neurovascular patients