418 research outputs found
Novel molecular pathologies in asthma and COPD
No full textBoth asthma and COPD are respiratory diseases and a major global health problem with
increasing prevalence. Airway inflammation is a characteristic and important hallmark in both
diseases and therefore, in the past, investigations focused strongly on the immunological aspect of
these disorders.
In recent years, it has been shown that resident cells of the airways, in particular airway smooth
muscle (ASM) cells, would be pivotal in understanding the mechanisms underlying asthma, since
they are able to secrete pro-inflammatory cytokines and exert a major effector function in airway
constriction. Especially the abnormal expression in ASM cells in asthmatic patients of the cell
cycle regulator and pro-inflammatory gene transcription factor C/EBPα may account for many
asthma-specific phenotypes (increased proliferation and increased bulk of ASM cells, increased
release of inflammatory mediators).
In a first phase, we analyzed the translation of the CEBPA mRNA with a translation control
reporter system (TCRS), which is able to monitor translation regulation of the C/EBPα. We found
an impaired translation re-initiaion in ASM cells of asthmatic patients, which coincided with
decreased levels of eIF4E, an important protein for translation initiation.
In a second part of this thesis, we investigated the interaction of ASM cells with house dust mite
extract, a potent airborne allergen. We found that HDM extract (i) reduces C/EBPα expression in
ASM cells of asthma patients, (ii) enhances the release of IL-6 and (iii) induces cell proliferation.
The reduction of the C/EBPα protein is achieved trough up-regulation of calreticulin, a repressor
of CEBPA mRNA translation. Therefore, the direct, not immune-mediated interaction of HDM
extract with the ASM cells is able to trigger an inflammatory response in these cells and to induce
an enhanced proliferation, which may finally lead to the characteristic increased muscle mass observed in the airway of asthmatic patients. These findings may be of particular importance to
explain non-atopic, intrinsic asthma, which affects 30% - 50% of asthmatic subjects. In the light
of these findings, new therapeutic strategies targeting regulatory mechanisms of CEBPA mRNA
translation should be considered in order to restore a balanced expression of the C/EBPα protein.
In a third part of this thesis, we investigated the effect of cigarette smoke on the expression levels
of C/EBPα and C/EBPβ in primary lung fibroblasts. Cigarette smoke affects both C/EBPα and C/EBPβ expression via translational control mechanisms in primary lung fibroblasts. In serumfree
environment, cigarette smoke increased both C/EBPα and -β expression at the translational
level via the uORF mechanism. In the presence of FCS, cigarette smoke increased the levels of
hnRNP E2, an inhibitor of C/EBPα translation. As a consequence, both C/EBPα and -β
expression decreased with increasing concentration of cigarette smoke. In both conditions,
cigarette smoke had a potent antiproliferative effect on fibroblasts. Furthermore, cigarette smoke
increased the release of IL-8. We postulate that the cigarette smoke-induced imbalance of proand
anti-proliferative signals provides a novel mechanism to explain many pathologies of COPD
and emphysema, especially the tissue destruction defined as an imbalance between tissue injury
and tissue repair. Furthermore, we showed that that the direct interaction of lung fibroblast with
cigarette smoke triggers the release of pro-inflammatory mediators, contributing to the
inflammatory environment that characterizes COPD
Probabilistic risk assessment modelling for passenger aircraft fire safety
No full textThis thesis describes the development
of a computer simulation model
for the
investigation
of airliner
fire
accident safety.
The
aim of the work
has been to create a computer-based analysis tool that generates
representative aircraft accident scenarios and then simulates their outcome
in terms of
passenger injuries
and
fatalities. The details
of the accident scenarios are
formulated
to closely match the type of events that are
known to have
occurred
in
aircraft
accidents over the last 40
years.
This information has been obtained
by
compiling a
database
and undertaking
detailed
analysis of approximately
200
airliner
fire
accidents. In
addition to utilising
historical data, the modelling work
has incorporated
many of the key findings
obtained
from
experimental research undertaken
by the
world's air safety community.
An
unusual
feature of the simulation process is that all critical aspects of the accident
scenario have been analysed and catered for in the formative
stages of the programme
development. This has
enabled complex effects, such as cabin crash
disruption,
impact trauma injuries, fire
spread, smoke
incapacitation
and passenger evacuation to
be
simulated
in
a
balanced and
integrated manner.
The
study
is intended to further the general appreciation and understanding of the
complex events that lead to fatalities in
aircraft
fire
accidents.
This is
achieved
by
analysing all contributory
factors that are
likely to arise
in
real
fire
accident scenarios
and undertaking quantitative risk assessment through the use of novel simulation
methods. Future development
of the research could potentially enable the undertaking
of a systematic exploration and appraisal of the effectiveness of
both
current and
future
aircraft
fire
safety policies
O Uso de animais no ensino e na pesquisa acadêmica: estilos de pensamento no fazer e ensinar ciência
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Educação. Programa de Pós-Graduação em Educação Científica e TecnológicaA experimentação animal é uma atividade bastante difundida no meio acadêmico e científico, e conta com séculos de história desde o seu estabelecimento. As finalidades desta prática são constantemente afirmadas e justificadas por uma parte considerável da comunidade científica, especialmente quanto ao emprego de animais como modelo para pesquisa de doenças e enfermidades humanas. Acredita-se que o modelo animal é um "reagente" biológico capaz de predizer, com considerável confiança, os efeitos de determinadas substâncias ou intervenções quando então aplicados em seres humanos. Ainda, a pesquisa com animais é considerada por muitos autores como sendo fundamental para a ciência. No entanto, a prática da experimentação em animais vem provocando consideráveis preocupações políticas e públicas, sendo notável a crescente polemização em torno do tema. Estima-se que mais de 100 milhões de animais sejam mortos por ano em atividades de pesquisa, consumindo aproximadamente 14 bilhões de dólares. Há ainda uma visível tendência de assimilação do conceito do 3Rs (Substituição, Redução e Refinamento) por parte da comunidade científica, e da alegada humanização no manuseio com animais. A configuração deste cenário suscita importantes reflexões sobre as abordagens e o contexto de formação de estudantes das áreas de Ciências Biológicas e da Saúde no ensino superior. Através da abordagem epistemológica sócio-histórica de Ludwik Fleck, esta pesquisa tem por objetivo (1) identificar e caracterizar os estilos de pensamento (EPs) atuais em relação ao uso de animais como modelo pelas Ciências Biomédicas; (2) identificar a afiliação, entre docentes vinculados a IFES, atuando nas áreas de Ciências Fisiológicas e Farmacêuticas, aos EPs identificados; (3) identificar e caracterizar o perfil potencialmente inovador ou tradicional de docentes e discentes atuantes nas áreas das Ciências Biológicas e da Saúde, em relação ao uso de animais no ensino e na pesquisa, e (4) estabelecer e caracterizar possíveis relações entre o EP encontrado entre docentes, com os perfis potencialmente inovadores ou tradicionais de pós-graduandos e graduandos de áreas de Ciências Biológicas e da Saúde. A hipótese desta pesquisa é a de que há um EP hegemônico que preconiza o modelo animal como indispensável para atividades de pesquisa e ensino nas Ciências Biológicas e da Saúde que dificulta o surgimento de novos EPs contrários ao mesmo. Para isso, foram aplicados questionários online a 185 docentes das áreas mencionadas; 140 estudantes de sete programas de Pós-graduação nas áreas mencionadas, e questionários presenciais a 406 estudantes de graduação de Medicina, Ciências Biológicas e Farmácia de duas IFES. Ainda, oito professores foram entrevistados. A pesquisa identificou e caracterizou dois EPs atuais em relação ao uso de animais nas Ciências Biomédicas. Como verificamos, estes dois EPs atuam sobre as mesmas questões de pesquisa, porém orientados por uma estrutura de ideias e práticas bastante diferenciadas. O EP mais antigo, denominado vivisseccionista, é atualmente o hegemônico. Esta hegemonia, construída ao longo dos séculos, e que permitiu uma grande sistematização do saber, estabeleceu uma harmonia na forma de se conceber o papel do modelo animal no empreendimento científico, considerado como essencial e inquestionável. No entanto, a pesquisa identificou sinais de declínio do atual EP, face às crescentes complicações identificadas e que propiciam o surgimento de um EP emergente e inovador, e com uma incipiente representatividade entre docentes e estudantes. Há, ao mesmo tempo, uma forte sintonia por parte da maioria dos estudantes, nas áreas de Ciências Biológicas e da Saúde, com perfis potencialmente tradicionais em relação ao emprego de animais em atividades de pesquisa, levando a crer que a atual abordagem da educação científica favorece a permanência de uma forma de pensar afinada com o EP hegemônico, corroborando a hipótese inicial da pesquisa. Os resultados ainda indicam que, apesar da forte tendência no estabelecimento do conceito dos 3Rs identificado na literatura e nas entrevistas, há pouca assimilação deste conceito tanto nas graduações quanto nas Pós-graduações investigadas. Diversas recomendações são propostas
Analysis of tobacco and cannabis smoke and its toxicological impact in neuroblastoma tumour cells
No full textDissertação de Erasmus Mundus para obtenção do grau de mestre em Técnicas Laboratoriais ForensesThe dried products of Cannabis sativa have been consumed for their psychoactive effects for thousands of years. Almost five hundred different natural cannabinoids could be identified in Cannabis sativa with Δ9-THC being the most psychoactive one. The most effective way of consumption is by smoking, because it avoids digestion and the first pass in the liver. Usually so called "joints" are rolled in a 1:1 ratio of dried cannabis and tobacco filler. The reason for this is that cannabis has a lower burning efficiency and that tobacco is cheaper. Processed Nicotina tabaccum contains about 0.6- 9 % nicotine; an oily, volatile liquid alkaloid. Pyrolysis of tobacco and cannabis leads to the formation of new products whose cytotoxicity is not yet established. This study investigates the effect of smoke of tobacco, cannabis and their mixture in similar conditions as humans uptake it. For production of smoke an in-house developed smoking device was used which trapped the water-soluble and organic-soluble molecules separately.
Qualitative analysis of the smoke was performed using GC-MS and measurement of cytotoxicity on neuroblastoma tumour cells SH-SY5Y was performed using the MTT assay.
SH-SY5Y cell line selectively expresses Cannabinoid 1 (CB1) receptor and Nicotinic acetylcholine receptor (nAChR). The results allow us to identify several pyrolysated products which are hydroxylated forms of nicotine and Δ9-THC. Moreover, MTT analysis strongly suggests different toxicological impact between smoke of tobacco, cannabis and their mixture. In fact our results points smoke from the mixture of tobacco and cannabis having the higher impact on cell viability followed by the smoke of tobacco which in turn is more toxic than smoke of cannabis, the least toxic compound out of these three. This study shows that at 100 μM cannabis has a cell viability of 80 % while tobacco and the mixture have around 40 %
Development and validation of an outdoor low-cost smoke monitor
No full text2017 Summer.Includes bibliographical references.Wildfires and prescribed fires produce emissions that are harmful to human health. These health effects, however, are difficult to quantify, likely in part due to sparse data on exposure. The ability to measure fire emissions as they reach sensitive areas is critical to ensuring the protection of public health. Ground level quantification of smoke from wildfires and prescribed fires has proven to be a difficult task. The state of the art for monitoring outdoor air quality has long relied upon expensive, cumbersome equipment that generally requires line power. Few ground-based measurements are typically made during fire events, which limits our ability to quantify and assess the impact of smoke from fire events. The objective of this work was to develop and validate a new type of outdoor air quality monitor, the Outdoor Aerosol Sampler (OAS). The OAS is an active, filter-based air sampler that has been miniaturized and weatherproofed. The OAS represents and attempt to address the technical limitations of field sampling with a device that is relatively inexpensive and independently powered. Prototype development of the OAS was made possible through low-cost electronics, open-source programming platforms, and in house fabrication methods. An online PM2.5 sensor was selected and integrated with the OAS. A Monte Carlo simulation aided in the selection of battery and solar power necessary to independently power the OAS, while keeping cost and size to a minimum. Cellular communications established via Short Message Service (SMS) technology were utilized in transmitting online sensor readings and controlling the OAS remotely. Numerous OAS were deployed to monitor smoke concentrations downwind from a large prescribed fire. Mass concentrations sampled from the burn were interpolated to depict smoke concentration gradients downwind of the fire. Field tests found OAS solar charging efficiency (6.7%) to be slightly less than model input efficiency (7.5%). Outdoor urban testing of the OAS demonstrates moderate agreement with equivalent federal reference method samplers for gravimetric analysis of PM2.5
Second Hand Tobacco Smoke Exposure among Adults in an Urbanized Village in Delhi
No full textBackground:
India contributes to the maximum of the world’s health burdens attributable to tobacco use. Exposure to secondhand smoke (SHS) is also associated with adverse health effects, causing 1.2 million deaths worldwide each year. In Delhi, 28.0% had SHS exposure at public places. About one-fifth experienced exposure to SHS at workplace. This study aimed to determine the prevalence of SHS exposure among adults in an urbanized village in Delhi.
Materials and Method:
It was a community-based cross-sectional house-to-house survey conducted between January 2020 and June 2021 in Aliganj, an urbanized village in Delhi. A total of 490 residents ≥15 years were included using simple random sampling. The interview was conducted by the primary author using the Global Adult Tobacco Survey (GATS). Each subject enrolled in the study was explicitly informed of the purpose of the study by the investigator and provided written informed consent before enrolment. Data were checked for errors, entered in Microsoft Excel, and analyzed in Statistical Package for the Social Sciences (SPSS).
Results:
Of the 490 participants, 14.7% were exposed to SHS in their house and 16.1% were exposed to SHS outside the house in the last 1 month. The majority (85.3%) believed secondhand smoking is harmful, 6.5% disagreed, and the rest were unaware.
Conclusion:
Though most participants knew that exposure to SHS can cause serious illness, further awareness sessions need to be conducted to improve knowledge and understanding and reduce exposure to secondhand tobacco smoke in homes. Strict adherence to no-smoking policies should be implemented as per law to reduce exposure to SHS in public areas
2006 Author Recognition Bibliography
No full texthttps://scholarworks.gvsu.edu/authorrecognition/1008/thumbnail.jp
Competition for morgue house at Barrancos, Portugal.
No full textMortuary House: an intimate space, a social space.
Inside: an intimate, spiritual space for recollection, introspection and prayer.
Outside: social meeting space, psychological relaxation, smiles and conversations, smoke and coffee, looking at the landscape in the shadow of the building it protects. It is a robust building, supported on volumes directly attached to the ground, and yet, seeming to be suspended, hovering over the slope.
The Barrancos Cemetery, located at the highest point of the village, offers a relationship with the sky full of symbolism. Our Mortuary House proposes a direct connection to the intermediate level, reusing and enhancing an existing secondary door, allowing easier access to the center of the Cemetery and, from there, making the route to the desired places, namely the platforms of the recent expansion.
The Mortuary House appears as a white volume, perpendicular to the equally white and prismatic bodies of the Cemetery. It is accessed from Rua de São Bento via a ramp, or via a staircase embraced by two small terraces that offer panoramic views over the surrounding landscape.
The staircase provides a leisurely and symbolic approach, descending to the wake spaces.
The Wake Rooms are conceived as spaces with a strong spiritual and symbolic charge.
In each room, a central corridor topped by a skylight leads to the marble plinth on which the urn rests, illuminated by the overhead light. Surrounding the walls, a bench also in Alentejo marble, is intended for the family and close friends of the loved one, symbolically embracing him. It is an intimate space, of the last homage. Separating the two rooms there will be a wall formed by sliding white panels, which go back to the Waiting Room, where they are rotated and arranged.
The Grand Wake Room, as a unique space, will be marked by the two large skylights over the corridors.
The marble-paved area, intended for family members and special friends, will embrace on both sides the urn that will be placed in the center, on the two marble benches that thus form the central plinth. The two plinths of the individual Wake Rooms will be mechanically lowered to the floor level, like simple marble slabs
Chirurgischer Rauch, eine Fragestellung der Hygiene, Toxikologie und des Arbeitsschutzes
No full textThe use of devices for tissue dissection and hemostasis during surgery is almost unavoidable. Electrically powered devices such as electrocautery, ultrasonic and laser units produce surgical smoke containing more than a thousand different products of combustion. These include large amounts of carcinogenic, mutagenic and potentially teratogenic noxae. The smoke contains particles that range widely in size, even as small as 0.007 µm. Most of the particles (90%) in electrocautery smoke are <=6.27 µm in size, but surgical masks cannot filter particles smaller than 5 µm. In this situation, 95% of the smoke particles which pass through the mask reach deep into the respiratory tract and frequently cause various symptoms, such as headache, dizziness, nausea, eye and respiratory tract irritation, weakness, and abdominal pain in the acute period. The smoke can transport bacteria and viruses that are mostly between 0.02 µm and 3 µm in size and there is a risk of contamination. Among these viruses, SARS-CoV-2, influenza virus, HIV, HPV, HBV must be considered. The smoke may also carry malignant cells. The long-term effects of the surgical smoke are always ignored, because causality can hardly be clarified in individual cases. The quantity of the smoke changes with the technique of the surgeon, the room ventilation system, the characteristics of the power device used, the energy level at which it is set, and the characteristics of the tissue processed. The surgical team is highly exposed to the smoke, with the surgeon experiencing the highest exposure. However, the severity of exposure differs according to certain factors, e.g., ventilation by laminar or turbulent mixed airflow or smoke evacuation system. In any case, the surgical smoke must be removed from the operation area. The most effective method is to collect the smoke from the source through an aspiration system and to evacuate it outside. Awareness and legal regulations in terms of hygiene, toxicology, as well as occupational health and safety should increase.Der Einsatz von Devices zur Gewebedissektion und Blutstillung während des Eingriffs ist im Allgemeinen unumgänglich. Elektrisch betriebene Devices wie Elektrokauter, Ultraschall- und Lasergeräte erzeugen chirurgischen Rauch, der mehr als tausend verschiedene Verbrennungsprodukte enthält. Darunter befinden sich große Mengen an krebserregenden, mutagenen und potentiell teratogene Noxen. Der Rauch enthält Partikel in einem weiten Größenspektrum, das bis zu 0,007 µm betragen kann. Die meisten Partikel (90%) im Elektrokauterisationsrauch sind <=6,27 µm groß. Chirurgische Masken können Partikel <5 µm nicht filtern. Daher gelangen 95% der durch die Maske gelangenden der Rauchpartikel tief in die Atemwege und verursachen in der akuten Phase häufig Symptome wie Kopfschmerz, Schwindel, Übelkeit, Reizungen der Augen und Atemwege, Schwäche und Bauchschmerzen. Der Rauch kann Bakterien und Viren transportieren, die meist zwischen 0,02 µm und 3 µm groß sind, so dass ein Kontaminationsrisiko besteht. Unter diesen Viren sind SARS-CoV-2, Influenzaviren, HIV, HPV und HBV zu nennen. Der Rauch kann auch Krebszellen enthalten. Langfristige Auswirkungen des OP-Rauchs werden stets ignoriert, da die Kausalität im Einzelfall kaum geklärt werden kann.Die Menge des Rauchs hängt von der Technik des Chirurgen, dem Belüftungssystem des Operationsraums, den Eigenschaften des verwendeten Devices, der eingestellten Energiestufe und den Eigenschaften des verarbeiteten Gewebes ab. Das Operationsteam ist in hohem Maße dem Rauch ausgesetzt, am stärksten jedoch der Chirurg. Das Ausmaß der Exposition hängt jedoch von verschiedenen Faktoren ab, insbesondere von der Art der Belüftung (laminare Luftströmung oder turbulente Mischströmung) und dem Rauchabzugssystem. In jedem Fall muss der chirurgische Rauch aus dem Operationsbereich entfernt werden. Die wirksamste Methode besteht darin, den Rauch durch ein Absaugsystem an der Quelle zu erfassen und ins Freie abzuführen. Abschließend ist festzustellen, dass das Bewusstsein und die gesetzlichen Vorschriften in Bezug auf Hygiene, Toxikologie, Arbeitsschutz und Sicherheit verbessert werden sollten
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