15,772 research outputs found

    Process intensification of oxidative coupling of methane

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    Identifizierung prädiktiver und prognostischer Biomarker in unterschiedlichen Tumorkompartimenten des ösophagealen Adenokarzinoms

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    Das ösophageale Adenokarzinom zeigt eine global steigende Inzidenz und hat mit einer 5-Jahres-Überlebensrate von weniger als 25% eine schlechte Prognose. Personalisierte Therapieansätze sind selten und prognostische/prädiktive Biomarker des Tumormikromilieus sind unzureichend charakterisiert. Die kumulative Promotion nähert sich dieser Problematik in drei unterschiedlichen Schwerpunkten. 1. Zur Identifizierung Kompartiment-spezifischer Biomarker wurde eine Methode entwickelt, welche als kostengünstige Alternative zum sc-Seq Expressionsprofile individueller Zelltypen generiert. Dabei erfolgt die Extraktion der RNA nicht aus Einzelzellen, sondern aus flowzytometrisch-getrennten Zellkompartimenten. Die Separation der Proben in Epithelzellen, Immunzellen und Fibroblasten wurde durch verschiedene Verfahren validiert und eine suffiziente Ausbeute an RNA auch für kleine Gewebemengen gezeigt. 2. Biomarker des Immunzellkompartiments als therapeutische Angriffspunkte wurden in einem Patientenkollektiv von bis zu 551 Patienten auf ihre Bedeutung beim EAC überprüft. Es zeigte sich eine Expression der Immuncheckpoints LAG3, VISTA und IDO auf TILs durch IHC und RNA-Sonden basierte Verfahren in einem relevanten Anteil (LAG3: 11,4%, VISTA: 29%, IDO: 52,6%). Es konnte eine prognostisch günstige Bedeutung der VISTA, LAG3 und IDO Expression gezeigt werden. Durch den Vergleich von Genexpressionsprofilen aus therapienaiven und vorbehandelten Tumoren konnte zudem ein immunsuppressiver Effekt von neoadjuvanten Therapiekonzepten auf das Tumormikromilieu des EACs gezeigt werden. Dabei kam es zur verminderten Expression von Checkpoints und Anzahl TILs nach (Radio-) Chemotherapie. 3. Im Tumorzellkompartiment wurde die Rolle von Amplifikationen in ErbB-Rezeptor abhängigen Signalwegen durch FISH-Technik und Immunhistochemie evaluiert. Es fanden sich KRAS Amplifikationen in 17,1%, PIK3CA Amplifikationen in 5% sowie eine HER2/neu-Überexpression in 14,9% der untersuchten Tumore

    The place where curses are manufactured : four poets of the Vietnam War

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    The Vietnam War was unique among American wars. To pinpoint its uniqueness, it was necessary to look for a non-American voice that would enable me to articulate its distinctiveness and explore the American character as observed by an Asian. Takeshi Kaiko proved to be most helpful. From his novel, Into a Black Sun, I was able to establish a working pair of 'bookends' from which to approach the poetry of Walter McDonald, Bruce Weigl, Basil T. Paquet and Steve Mason. Chapter One is devoted to those seemingly mismatched 'bookends,' Walt Whitman and General William C. Westmoreland, and their respective anthropocentric and technocentric visions of progress and the peculiarly American concept of the "open road" as they manifest themselves in Vietnam. In Chapter, Two, I analyze the war poems of Walter McDonald. As a pilot, writing primarily about flying, his poetry manifests General Westmoreland's technocentric vision of the 'road' as determined by and manifest through technology. Chapter Three focuses on the poems of Bruce Weigl. The poems analyzed portray the literal and metaphorical descent from the technocentric, 'numbed' distance of aerial warfare to the world of ground warfare, and the initiation of a 'fucking new guy,' who discovers the contours of the self's interior through a set of experiences that lead from from aerial insertion into the jungle to the degradation of burning human feces. Chapter Four, devoted to the thirteen poems of Basil T. Paquet, focuses on the continuation of the descent begun in Chapter Two. In his capacity as a medic, Paquet's entire body of poems details his quotidian tasks which entail tending the maimed, the mortally wounded and the dead. The final chapter deals with Steve Mason's JohnnY's Song, and his depiction of the plight of Vietnam veterans back in "The World" who are still trapped inside the interior landscape of their individual "ghettoes" of the soul created by their war-time experiences

    Metal−Organic Frameworks in Agriculture

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    The work has been supported by the MOFSEIDON project (PID2019-104228RB-100) funded by MCI/AEI/10.13039/ 501100011033/FEDER “Una manera de hacer Europa”, ESENCE project (RTC2019-007254-5) funded by MCIN/ AEI/10.13039/501100011033), Junta de Andalucía (FQM- 394), and the Multifunctional Metallodrugs in Diagnosis and Therapy Network (MICIU, RED2018-102471-T). P.H. acknowledges the Spanish Ramón y Cajal Programme (grant agreement 2014-15039). S.R. acknowledges the Spanish Juan de la Cierva Incorporación Fellowship (grant agreement no. IJC2019-038894-I) funded by MCIN/AEI/10.13039/ 501100011033. Funding for open access charge: Universidad de Granada/CBUA.Agrochemicals, which are crucial to meet the world food qualitative and quantitative demand, are compounds used to kill pests (insects, fungi, rodents, or unwanted plants). Regrettably, there are some important issues associated with their widespread and extensive use (e.g., contamination, bioaccumulation, and development of pest resistance); thus, a reduced and more controlled use of agrochemicals and thorough detection in food, water, soil, and fields are necessary. In this regard, the development of new functional materials for the efficient application, detection, and removal of agrochemicals is a priority. Metal–organic frameworks (MOFs) with exceptional sorptive, recognition capabilities, and catalytical properties have very recently shown their potential in agriculture. This Review emphasizes the recent advances in the use of MOFs in agriculture through three main views: environmental remediation, controlled agrochemical release, and detection of agrochemicals.MOFSEIDON project (PID2019-104228RB-100) funded by MCI/AEI/10.13039/ 501100011033/FEDERESENCE project (RTC2019-007254-5) funded by MCIN/ AEI/10.13039/501100011033Junta de Andalucía (FQM- 394), and the Multifunctional Metallodrugs in Diagnosis and Therapy Network (MICIU, RED2018-102471-T)Spanish Ramón y Cajal Programme (grant agreement 2014-15039)Spanish Juan de la Cierva Incorporación Fellowship (grant agreement no. IJC2019-038894-I) funded by MCIN/AEI/10.13039/ 501100011033Funding for open access charge: Universidad de Granada/CBU

    Review of Methodologies to Assess Bridge Safety During and After Floods

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    This report summarizes a review of technologies used to monitor bridge scour with an emphasis on techniques appropriate for testing during and immediately after design flood conditions. The goal of this study is to identify potential technologies and strategies for Illinois Department of Transportation that may be used to enhance the reliability of bridge safety monitoring during floods from local to state levels. The research team conducted a literature review of technologies that have been explored by state departments of transportation (DOTs) and national agencies as well as state-of-the-art technologies that have not been extensively employed by DOTs. This review included informational interviews with representatives from DOTs and relevant industry organizations. Recommendations include considering (1) acquisition of tethered kneeboard or surf ski-mounted single-beam sonars for rapid deployment by local agencies, (2) acquisition of remote-controlled vessels mounted with single-beam and side-scan sonars for statewide deployment, (3) development of large-scale particle image velocimetry systems using remote-controlled drones for stream velocity and direction measurement during floods, (4) physical modeling to develop Illinois-specific hydrodynamic loading coefficients for Illinois bridges during flood conditions, and (5) development of holistic risk-based bridge assessment tools that incorporate structural, geotechnical, hydraulic, and scour measurements to provide rapid feedback for bridge closure decisions.IDOT-R27-SP50Ope

    Coloniality and the Courtroom: Understanding Pre-trial Judicial Decision Making in Brazil

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    This thesis focuses on judicial decision making during custody hearings in Rio de Janeiro, Brazil. The impetus for the study is that while national and international protocols mandate the use of pre-trial detention only as a last resort, judges continue to detain people pre-trial in large numbers. Custody hearings were introduced in 2015, but the initiative has not produced the reduction in pre-trial detention that was hoped. This study aims to understand what informs judicial decision making at this stage. The research is approached through a decolonial lens to foreground legacies of colonialism, overlooked in mainstream criminological scholarship. This is an interview-based study, where key court actors (judges, prosecutors, and public defenders) and subject matter specialists were asked about influences on judicial decision making. Interview data is complemented by non-participatory observation of custody hearings. The research responds directly to Aliverti et al.'s (2021) call to ‘decolonize the criminal question’ by exposing and explaining how colonialism informs criminal justice practices. Answering the call in relation to judicial decision making, findings provide evidence that colonial-era assumptions, dynamics, and hierarchies were evident in the practice of custody hearings and continue to inform judges’ decisions, thus demonstrating the coloniality of justice. This study is significant for the new empirical data presented and theoretical innovation is also offered via the introduction of the ‘anticitizen’. The concept builds on Souza’s (2007) ‘subcitizen’ to account for the active pursuit of dangerous Others by judges casting themselves as crime fighters in a modern moral crusade. The findings point to the limited utility of human rights discourse – the normative approach to influencing judicial decision making around pre-trial detention – as a plurality of conceptualisations compete for dominance. This study has important implications for all actors aiming to reduce pre-trial detention in Brazil because unless underpinning colonial logics are addressed, every innovation risks becoming the next lei para inglês ver (law [just] for the English to see)

    Post-Millennial Queer Sensibility: Collaborative Authorship as Disidentification in Queer Intertextual Commodities

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    This dissertation is examining LGBTQ+ audiences and creatives collaborating in the creation of new media texts like web shows, podcasts, and video games. The study focuses on three main objects or media texts: Carmilla (web series), Welcome to Night Vale (podcast), and Undertale (video game). These texts are transmedia objects or intertextual commodities. I argue that by using queer gestures of collaborative authorship that reaches out to the audience for canonical contribution create an emerging queer production culture that disidentifies with capitalism even as it negotiates capitalistic structures. The post-millennial queer sensibility is a constellation of aesthetics, self-representation, alternative financing, and interactivity that prioritizes community, trust, and authenticity using new technologies for co-creation. Within my study, there are four key tactics or queer gestures being explored: remediation, radical ambiguity and multi-forms as queer aesthetics, audience self-representation, alternative financing like micropatronage & licensed fan-made merchandise, and interactivity as performance. The goal of this project is to better understand the changing conceptions of authorship/ownership, canon/fanon (official text/fan created extensions), and community/capitalism in queer subcultures as an indicator of the potential change in more mainstream cultural attitudes. The project takes into consideration a variety of intersecting identities including gender, race, class, and of course sexual orientation in its analysis. By examining the legal discourse around collaborative authorship, the real-life production practices, and audience-creator interactions and attitudes, this study provides insight into how media creatives work with audiences to co-create self-representative media, the motivations, and rewards for creative, audiences, and owners. This study aims to contribute towards a fuller understanding of queer production cultures and audience reception of these media texts, of which there is relatively little academic information. Specifically, the study mines for insights into the changing attitudes towards authorship, ownership, and collaboration within queer indie media projects, especially as these objects are relying on the self-representation of both audiences and creatives in the formation of the text

    Towards A Graphene Chip System For Blood Clotting Disease Diagnostics

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    Point of care diagnostics (POCD) allows the rapid, accurate measurement of analytes near to a patient. This enables faster clinical decision making and can lead to earlier diagnosis and better patient monitoring and treatment. However, despite many prospective POCD devices being developed for a wide range of diseases this promised technology is yet to be translated to a clinical setting due to the lack of a cost-effective biosensing platform.This thesis focuses on the development of a highly sensitive, low cost and scalable biosensor platform that combines graphene with semiconductor fabrication tech-niques to create graphene field-effect transistors biosensor. The key challenges of designing and fabricating a graphene-based biosensor are addressed. This work fo-cuses on a specific platform for blood clotting disease diagnostics, but the platform has the capability of being applied to any disease with a detectable biomarker.Multiple sensor designs were tested during this work that maximised sensor ef-ficiency and costs for different applications. The multiplex design enabled different graphene channels on the same chip to be functionalised with unique chemistry. The Inverted MOSFET design was created, which allows for back gated measurements to be performed whilst keeping the graphene channel open for functionalisation. The Shared Source and Matrix design maximises the total number of sensing channels per chip, resulting in the most cost-effective fabrication approach for a graphene-based sensor (decreasing cost per channel from £9.72 to £4.11).The challenge of integrating graphene into a semiconductor fabrication process is also addressed through the development of a novel vacuum transfer method-ology that allows photoresist free transfer. The two main fabrication processes; graphene supplied on the wafer “Pre-Transfer” and graphene transferred after met-allisation “Post-Transfer” were compared in terms of graphene channel resistance and graphene end quality (defect density and photoresist). The Post-Transfer pro-cess higher quality (less damage, residue and doping, confirmed by Raman spec-troscopy).Following sensor fabrication, the next stages of creating a sensor platform involve the passivation and packaging of the sensor chip. Different approaches using dielec-tric deposition approaches are compared for passivation. Molecular Vapour Deposi-tion (MVD) deposited Al2O3 was shown to produce graphene channels with lower damage than unprocessed graphene, and also improves graphene doping bringing the Dirac point of the graphene close to 0 V. The packaging integration of microfluidics is investigated comparing traditional soft lithography approaches and the new 3D printed microfluidic approach. Specific microfluidic packaging for blood separation towards a blood sampling point of care sensor is examined to identify the laminar approach for lower blood cell count, as a method of pre-processing the blood sample before sensing.To test the sensitivity of the Post-Transfer MVD passivated graphene sensor de-veloped in this work, real-time IV measurements were performed to identify throm-bin protein binding in real-time on the graphene surface. The sensor was function-alised using a thrombin specific aptamer solution and real-time IV measurements were performed on the functionalised graphene sensor with a range of biologically relevant protein concentrations. The resulting sensitivity of the graphene sensor was in the 1-100 pg/ml concentration range, producing a resistance change of 0.2% per pg/ml. Specificity was confirmed using a non-thrombin specific aptamer as the neg-ative control. These results indicate that the graphene sensor platform developed in this thesis has the potential as a highly sensitive POCD. The processes developed here can be used to develop graphene sensors for multiple biomarkers in the future

    A Molecular Approach to the Diagnosis, Assessment, Monitoring and Treatment of Pulmonary Non-Tuberculous Mycobacterial Disease

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    Introduction: Non-Tuberculous Mycobacteria (NTM) can cause disease of the lungs and sinuses, lymph nodes, joints and central nervous system as well as disseminated infections in immunocompromised individuals. Efforts to tackle infections in NTM are hampered by a lack of reliable biomarkers for diagnosis, assessment of disease activity, and prognostication. Aims: The broad aims of this thesis are: 1. to develop molecular assays capable of quantifying the 6 most common pathogenic mycobacteria (M. abscessus, M. avium, M. intracellulare, M. malmoense, M. kansasii, M. xenopi) and calculate comparative sensitivities and specificities for each assay. 2. to assess patients’ clinical course over 12 – 18 months by performing the developed molecular assays against DNA extracted from sputum from patients with NTM infection. 3. to assess dynamic bacterial changes of the lung microbiome in patients on treatment for NTM disease and those who are treatment na ve. Methods: DNA was extracted from a total of 410 sputum samples obtained from 38 patients who were either: • commencing treatment for either M. abscessus or Mycobacterium avium complex. • considered colonised with M. abscessus or Mycobacterium avium complex (i.e. cultured NTM but were not deemed to have infection as they did not meet ATS or BTS criteria for disease). • Diagnosed with cystic fibrosis (CF) or non-CF bronchiectasis but had never cultured NTM. For the development of quantitative molecular assays, NTM hsp65 gene sequences were aligned and interrogated for areas of variability. These variable regions enabled the creation of species specific probes. In vitro sensitivity and specificity for each probe was determined by testing each probe against a panel of plasmids containing hsp65 gene inserts from different NTM species. Quantification accuracy was determined by using each assay against a mock community containing serial dilutions of target DNA. Each sample was tested with the probes targeting: M. abscessus, M. avium and M. intracellulare producing a longitudinal assessment of NTM copy number during each patient’s clinical course. In addition, a total of 64 samples from 16 patients underwent 16S rRNA gene sequencing to characterise longitudinal changes in the microbiome of both NTM disease and controls. Results: In vitro sensitivity for the custom assays were 100% and specificity ranged from 91.6% to 100%. In terms of quantification accuracy, there was no significant difference between the measured results of each assay and the expected values when performed in singleplex. The assays were able to accurately determine NTM copy number to a theoretical limit of 10 copies/μl. When used against samples derived from human sputum and using culture results as a gold standard, the sensitivity of the assay for M. abscessus was found to be 0.87 and 0.86 for MAC. The specificity of the assay for M. abscessus was 0.95 and 0.62 for MAC. The negative predictive value of the assay for M. abscessus was 0.98 and 0.95 for MAC. This resulted in an AUC of 0.92 for M. abscessus and 0.74 for MAC. Longitudinal analysis of the lung microbiome using 16SrRNA gene sequencing showed that bacterial burden initially decreases after initiation of antibiotic therapy but begins to return to normal levels over several months of antibiotic therapy. This effect is mirrored by changes in alpha diversity. The decrease in bacterial burden and loss of alpha diversity was found to be secondary to significant changes in specific genera such as Veillonella and Streptococcus. The abundance of other Proteobacteria such as Pseudomonas remain relatively constant. Conclusion: The molecular assay has shown high in vitro sensitivity and specificity for the detection and accurate quantification of the 6 most commonly pathogenic NTM species. The assays successfully identified NTM DNA from human sputum samples. A notable association between NTM copy number and the cessation of one or more antibiotics existed (i.e. when one antibiotic was stopped because of patient intolerance, NTM copy number increased, often having been unrecordable prior to this). The qPCR assays developed in this thesis provide an affordable, real time and rapid measurement of NTM burden allowing clinicians to act on problematic results sooner than currently possible. There was no significant difference between the microbiome in bronchiectasis and cystic fibrosis nor was there a significant difference between the microbiome in patients requiring treatment for NTM and those who did not. Patients receiving treatment experienced an initial decrease in bacterial burden over the first weeks of treatment followed by a gradual increase towards baseline over the next weeks to months. This change was mirrored in measures of alpha diversity. Changes in abundance and diversity were accounted for by decreases in specific bacteria whilst the abundance of other bacteria increased, occupying the microbial niche created. These bacteria (for example Pseudomonas spp) are often associated with morbidity.Open Acces

    The Adirondack Chronology

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    The Adirondack Chronology is intended to be a useful resource for researchers and others interested in the Adirondacks and Adirondack history.https://digitalworks.union.edu/arlpublications/1000/thumbnail.jp
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