17,337 research outputs found
Jack Derangements
For each integer partition we give a simple combinatorial
expression for the sum of the Jack character over the
integer partitions of with no singleton parts. For this
gives closed forms for the eigenvalues of the permutation and perfect matching
derangement graphs, resolving an open question in algebraic graph theory. A
byproduct of the latter is a simple combinatorial formula for the immanants of
the matrix where is the all-ones matrix, which might be of
independent interest. Our proofs center around a Jack analogue of a hook
product related to Cayley's --process in classical invariant theory,
which we call the principal lower hook product
Pollution-induced community tolerance in freshwater biofilms – from molecular mechanisms to loss of community functions
Exposure to herbicides poses a threat to aquatic biofilms by affecting their community structure, physiology and function. These changes render biofilms to become more tolerant, but on the downside community tolerance has ecologic costs. A concept that addresses induced community tolerance to a pollutant (PICT) was introduced by Blanck and Wängberg (1988). The basic principle of the concept is that microbial communities undergo pollution-induced succession when exposed to a pollutant over a long period of time, which changes communities structurally and functionally and enhancing tolerance to the pollutant exposure. However, the mechanisms of tolerance and the ecologic consequences were hardly studied up to date. This thesis addresses the structural and functional changes in biofilm communities and applies modern molecular methods to unravel molecular tolerance mechanisms.
Two different freshwater biofilm communities were cultivated for a period of five weeks, with one of the communities being contaminated with 4 μg L-1 diuron. Subsequently, the communities were characterized for structural and functional differences, especially focusing on their crucial role of photosynthesis. The community structure of the autotrophs was assessed using HPLC-based pigment analysis and their functional alterations were investigated using Imaging-PAM fluorometry to study photosynthesis and community oxygen profiling to determine net primary production. Then, the molecular fingerprints of the communities were measured with meta-transcriptomics (RNA-Seq) and GC-based community metabolomics approaches and analyzed with respect to changes in their molecular functions. The communities were acute exposed to diuron for one hour in a dose-response design, to reveal a potential PICT and uncover related adaptation to diuron exposure. The combination of apical and molecular methods in a dose-response design enabled the linkage of functional effects of diuron exposure and underlying molecular mechanisms based on a sensitivity analysis.
Chronic exposure to diuron impaired freshwater biofilms in their biomass accrual. The contaminated communities particularly lost autotrophic biomass, reflected by the decrease in specific chlorophyll a content. This loss was associated with a change in the molecular fingerprint of the communities, which substantiates structural and physiological changes. The decline in autotrophic biomass could be due to a primary loss of sensitive autotrophic organisms caused by the selection of better adapted species in the course of chronic exposure. Related to this hypothesis, an increase in diuron tolerance has been detected in the contaminated communities and molecular mechanisms facilitating tolerance have been found. It was shown that genes of the photosystem, reductive-pentose phosphate cycle and arginine metabolism were differentially expressed among the communities and that an increased amount of potential antioxidant degradation products was found in the contaminated communities. This led to the hypothesis that contaminated communities may have adapted to oxidative stress, making them less sensitive to diuron exposure. Moreover, the photosynthetic light harvesting complex was altered and the photoprotective xanthophyll cycle was increased in the contaminated communities. Despite these adaptation strategies, the loss of autotrophic biomass has been shown to impair primary production. This impairment persisted even under repeated short-term exposure, so that the tolerance mechanisms cannot safeguard primary production as a key function in aquatic systems.:1. The effect of chemicals on organisms and their functions .............................. 1
1.1 Welcome to the anthropocene .......................................................................... 1
1.2 From cellular stress responses to ecosystem resilience ................................... 3
1.2.1 The individual pursuit for homeostasis ....................................................... 3
1.2.2 Stability from diversity ................................................................................. 5
1.3 Community ecotoxicology - a step forward in monitoring the effects of chemical
pollution? ................................................................................................................. 6
1.4 Functional ecotoxicological assessment of microbial communities ................... 9
1.5 Molecular tools – the key to a mechanistic understanding of stressor effects
from a functional perspective in microbial communities? ...................................... 12
2. Aims and Hypothesis ......................................................................................... 14
2.1 Research question .......................................................................................... 14
2.2 Hypothesis and outline .................................................................................... 15
2.3 Experimental approach & concept .................................................................. 16
2.3.1 Aquatic freshwater biofilms as model community ..................................... 16
2.3.2 Diuron as model herbicide ........................................................................ 17
2.3.3 Experimental design ................................................................................. 18
3. Structural and physiological changes in microbial communities after chronic
exposure - PICT and altered functional capacity ................................................. 21
3.1 Introduction ..................................................................................................... 21
3.2 Methods .......................................................................................................... 23
3.2.1 Biofilm cultivation ...................................................................................... 23
3.2.2 Dry weight and autotrophic index ............................................................. 23
3.2.4 Pigment analysis of periphyton ................................................................. 23
3.2.4.1 In-vivo pigment analysis for community characterization ....................... 24
3.2.4.2 In-vivo pigment analysis based on Imaging-PAM fluorometry ............... 24
3.2.4.3 In-vivo pigment fluorescence for tolerance detection ............................. 26
3.2.4.4 Ex-vivo pigment analysis by high-pressure liquid-chromatography ....... 27
3.2.5 Community oxygen metabolism measurements ....................................... 28
3.3 Results and discussion ................................................................................... 29
3.3.1 Comparison of the structural community parameters ............................... 29
3.3.2 Photosynthetic activity and primary production of the communities after
selection phase ................................................................................................. 33
3.3.3 Acquisition of photosynthetic tolerance .................................................... 34
3.3.4 Primary production at exposure conditions ............................................... 36
3.3.5 Tolerance detection in primary production ................................................ 37
3.4 Summary and Conclusion ........................................................................... 40
4. Community gene expression analysis by meta-transcriptomics ................... 41
4.1 Introduction to meta-transcriptomics ............................................................... 41
4.2. Methods ......................................................................................................... 43
4.2.1 Sampling and RNA extraction................................................................... 43
4.2.2 RNA sequencing analysis ......................................................................... 44
4.2.3 Data assembly and processing................................................................. 45
4.2.4 Prioritization of contigs and annotation ..................................................... 47
4.2.5 Sensitivity analysis of biological processes .............................................. 48
4.3 Results and discussion ................................................................................... 48
4.3.1 Characterization of the meta-transcriptomic fingerprints .......................... 49
4.3.2 Insights into community stress response mechanisms using trend analysis
(DRomic’s) ......................................................................................................... 51
4.3.3 Response pattern in the isoform PS genes .............................................. 63
4.5 Summary and conclusion ................................................................................ 65
5. Community metabolome analysis ..................................................................... 66
5.1 Introduction to community metabolomics ........................................................ 66
5.2 Methods .......................................................................................................... 68
5.2.1 Sampling, metabolite extraction and derivatisation................................... 68
5.2.2 GC-TOF-MS analysis ............................................................................... 69
5.2.3 Data processing and statistical analysis ................................................... 69
5.3 Results and discussion ................................................................................... 70
5.3.1 Characterization of the metabolic fingerprints .......................................... 70
5.3.2 Difference in the metabolic fingerprints .................................................... 71
5.3.3 Differential metabolic responses of the communities to short-term exposure
of diuron ............................................................................................................ 73
5.4 Summary and conclusion ................................................................................ 78
6. Synthesis ............................................................................................................. 79
6.1 Approaches and challenges for linking molecular data to functional
measurements ...................................................................................................... 79
6.2 Methods .......................................................................................................... 83
6.2.1 Summary on the data ............................................................................... 83
6.2.2 Aggregation of molecular data to index values (TELI and MELI) .............. 83
6.2.3 Functional annotation of contigs and metabolites using KEGG ................ 83
6.3 Results and discussion ................................................................................... 85
6.3.1 Results of aggregation techniques ........................................................... 85
6.3.2 Sensitivity analysis of the different molecular approaches and endpoints 86
6.3.3 Mechanistic view of the molecular stress responses based on KEGG
functions ............................................................................................................ 89
6.4 Consolidation of the results – holistic interpretation and discussion ............... 93
6.4.1 Adaptation to chronic diuron exposure - from molecular changes to
community effects.............................................................................................. 93
6.4.2 Assessment of the ecological costs of Pollution-induced community
tolerance based on primary production ............................................................. 94
6.5 Outlook ............................................................................................................ 9
Quantum dots based superluminescent diodes and photonic crystal surface emitting lasers
This thesis reports the design, fabrication, and electrical and optical characterisations of GaAs-based quantum dot (QD) photonic devices, specifically focusing on superluminescent diodes (SLDs) and photonic crystal surface-emitting lasers (PCSELs). The integration of QD active regions in these devices is advantageous due to their characteristics such as temperature insensitivity, feedback insensitivity, and ability to utilise the ground state (GS) and excited state (ES) of the dots.
In an initial study concerning the fabrication of QD-SLDs, the influence of ridge waveguide etch depth on the electrical and optical properties of the devices are investigated. It is shown that the output power and modal gain from shallow etched ridge waveguide is higher than those of deep etched waveguides. Subsequently, the thermal performance of the devices is analysed. With increased temperature over 170 ºC, the spectral bandwidth is dramatically increased by thermally excited carrier transition in excited states of the dots.
Following this, an investigation of a high dot density hybrid quantum well/ quantum dot (QW/QD) active structure for broadband, high-modal gain SLDs is presented. The influence of the number of QD layers on the modal gain of hybrid QW/QD structures is analysed. It is shown that higher number of dot layer provides higher modal gain value, however, there is lack of emission from QW due to the requirement of large number of carriers to saturate the QD. Additionally, a comparison is made between “unchirped QD” and “ chirped QD” of hybrid QW/QD structure in terms of modal gain and spectral bandwidth. It is showed that “chirped” of the QD can improve the “flatness” of the spectral bandwidth.
Lastly, the use of self-assembled InAs QD as the active material in epitaxially regrown GaAs-based PCSELs is explored for the first time. Initially, it is shown that both GS and ES lasing can be achieved for QD-PCSELs by changing the grating period of the photonic crystal (PC). The careful design of these grating periods allows lasing from neighbouring devices at GS ( ~1230 nm) and ES (~1140 nm), 90 nm apart in wavelength. Following this, the effect of device area, PC etch depth, PC atom shape (circle or triangle or orientation) on lasing performance is presented. It is shown that lower threshold current density and higher slope efficiencies is achieved with increasing the device size. The deeper PC height device has higher output power due to more suitable height and minimal distance to active region. The triangular atom shape has slightly higher slope efficiency compared to triangular atom shape which is attributed to breaking in-plane symmetry and increase out-of-plane emission
Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico
Valve replacement remains as the standard therapeutic option for aortic
stenosis patients, aiming at abolishing pressure overload and triggering
myocardial reverse remodeling. However, despite the instant hemodynamic
benefit, not all patients show complete regression of myocardial hypertrophy,
being at higher risk for adverse outcomes, such as heart failure. The current
comprehension of the biological mechanisms underlying an incomplete reverse
remodeling is far from complete. Furthermore, definitive prognostic tools and
ancillary therapies to improve the outcome of the patients undergoing valve
replacement are missing. To help abridge these gaps, a combined myocardial
(phospho)proteomics and pericardial fluid proteomics approach was followed,
taking advantage of human biopsies and pericardial fluid collected during
surgery and whose origin anticipated a wealth of molecular information
contained therein.
From over 1800 and 750 proteins identified, respectively, in the myocardium
and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated
proteins were detected. Gene annotation and pathway enrichment analyses,
together with discriminant analysis, are compatible with a scenario of increased
pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by
complement activity and other extrinsic factors, such as death receptor
activators), acute-phase response, immune system activation and fibrosis.
Specific validation of some targets through immunoblot techniques and
correlation with clinical data pointed to complement C3 β chain, Muscle Ring
Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation
regulated kinase 1A (DYRK1A) as potential markers of an incomplete
response. In addition, kinase prediction from phosphoproteome data suggests
that the modulation of casein kinase 2, the family of IκB kinases, glycogen
synthase kinase 3 and DYRK1A may help improve the outcome of patients
undergoing valve replacement. Particularly, functional studies with DYRK1A+/-
cardiomyocytes show that this kinase may be an important target to treat
cardiac dysfunction, provided that mutant cells presented a different response
to stretch and reduced ability to develop force (active tension).
This study opens many avenues in post-aortic valve replacement reverse
remodeling research. In the future, gain-of-function and/or loss-of-function
studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic
targets. Besides, clinical studies in larger cohorts will bring definitive proof of
complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de
referência para doentes com estenose aórtica e visa a eliminação da
sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica.
Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes
apresentam regressão completa da hipertrofia do miocárdio, ficando com maior
risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os
mecanismos biológicos subjacentes a uma remodelagem reversa incompleta
ainda não são claros. Além disso, não dispomos de ferramentas de
prognóstico definitivos nem de terapias auxiliares para melhorar a condição
dos pacientes indicados para substituição da válvula. Para ajudar a resolver
estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica
para a caracterização, respetivamente, do miocárdio e do líquido pericárdico
foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em
ambiente cirúrgico.
Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio
e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90
proteínas desreguladas foram detetadas. As análises de anotação de genes,
de enriquecimento de vias celulares e discriminativa corroboram um cenário de
aumento da expressão de genes pro-hipertróficos e de síntese proteica, um
sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular
(potencialmente acelerada pela atividade do complemento e por outros fatores
extrínsecos que ativam death receptors), com ativação da resposta de fase
aguda e do sistema imune, assim como da fibrose.
A validação de alguns alvos específicos através de immunoblot e correlação
com dados clínicos apontou para a cadeia β do complemento C3, a Muscle
Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation
regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta
incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma,
sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a
glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição
dos pacientes indicados para intervenção. Em particular, a avaliação funcional
de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo
importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes
responderam de forma diferente ao estiramento e mostraram uma menor
capacidade para desenvolver força (tensão ativa).
Este estudo levanta várias hipóteses na investigação da remodelagem reversa.
No futuro, estudos de ganho e/ou perda de função realizados em
cardiomiócitos isolados ou em modelos animais de banding-debanding da
aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos
encontrados. Além disso, estudos clínicos em coortes de maior dimensão
trarão conclusões definitivas quanto ao valor de prognóstico do complemento
C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin
Moduli Stabilisation and the Statistics of Low-Energy Physics in the String Landscape
In this thesis we present a detailed analysis of the statistical properties of the type IIB flux landscape of string theory. We focus primarily on models constructed via the Large Volume Scenario (LVS) and KKLT and study the distribution of various phenomenologically relevant quantities. First, we compare our considerations with previous results and point out the importance of Kähler moduli stabilisation, which has been neglected in this context so far. We perform different moduli stabilisation procedures and compare the resulting distributions. To this end, we derive the expressions for the gravitino mass, various quantities related to axion physics and other phenomenologically interesting quantities in terms of the fundamental flux dependent quantities , and , the parameter which specifies the nature of the non-perturbative effects. Exploiting our knowledge of the distribution of these fundamental parameters, we can derive a distribution for all the quantities we are interested in. For models that are stabilised via LVS we find a logarithmic distribution, whereas for KKLT and perturbatively stabilised models we find a power-law distribution. We continue by investigating the statistical significance of a newly found class of KKLT vacua and present a search algorithm for such constructions. We conclude by presenting an application of our findings. Given the mild preference for higher scale supersymmetry breaking, we present a model of the early universe, which allows for additional periods of early matter domination and ultimately leads to rather sharp predictions for the dark matter mass in this model. We find the dark matter mass to be in the very heavy range
Influence of local PO₂ on skeletal muscle microvascular blood flow during hyperinsulinemia
The goal of this thesis was to test the hypothesis that insulin mediated hyperemia is partially dependent on local muscle oxygen concentration. To do so, microvascular blood flow was measured in response to varying imposed concentrations of oxygen in rat skeletal muscle. Sprague-Dawley rats were anesthetized, and the extensor digitorum longus (EDL) was reflected onto an inverted microscope. Intravital video microscopy sequences were recorded during baseline and hyperinsulinemic euglycemia. The muscle was reflected over a glass stage insert (Experiment 1a and 1b), or over a gas exchange chamber (Experiment 2), and microvascular capillary blood flow was recorded during sequential changes (7%-12%-2%-7%) of oxygen (O₂) concentration. Blood flow was measured by the red blood cell supply rate (SR) in number of cells per second. In Experiment 1a, supply rate (SR) increased from 8.0 to 14 cells/s at baseline to euglycemia (p = 0.01), while no significant SR variation was detected after performing a sham hyperinsulinemic euglycemic clamp (Experiment 1b). In Experiment 2, SR decreased at 12% O₂ and increased at 2% O₂, compared to 7% O₂, under both experimental conditions. SR responses to oxygen square wave oscillations during euglycemia were not different to those at baseline at each O₂ concentration (p > 0.9). Our results suggest the increase in blood flow observed in response to insulin is eliminated if tissue oxygen microenvironment is clamped at given oxygen concentrations.
All animal protocols were approved by Memorial University’s Institutional Animal Care Committee
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Co-design As Healing: Exploring The Experiences Of Participants Facing Mental Health Problems
This thesis is an exploration of the healing role of co-design in mental health. Although co-design projects conducted within mental health settings are rising, existing literature tends to focus on the object of design and its outcomes while the experiences of participants per se remain largely unexplored. The guiding research question of this study is not how we design things that improve mental health, but how co-designing, as an act, might do so.
The thesis presents two projects that were organized in collaboration with the mental health charity Islington Mind and the Psychosis Therapy Project (PTP) in London.
The project at Islington Mind used a structured design process inviting participants to design for wellbeing. A case study analysis provides insights on how participants were impacted, summarizing key challenges and opportunities.
The design at PTP worked towards creating a collective brief in an emergent fashion, finally culminating in a board game. The experiences of participants were explored through Interpretative Phenomenological Analysis (IPA), using semi-structured interview data. The analysis served to identify key themes characterising the experience of co-design such as contributing, connecting, thinking and intentioning. In addition, a mixed-methods analysis of questionnaires and interview data exploring participants' wellbeing, showed that all participants who engaged fairly consistently in the project improved after the project ended, although some participants' scores returned to baseline six months later.
Reflecting on both projects, an approach to facilitation within mental health is outlined, detailing how the dimensions of weaving and layered participation, nurturing mattering and facilitating attitudes interlace. This contribution raises awareness of tacit dimensions in the practice of facilitation, articulating the nuances of how to encourage and sustain meaningful and ethical engagement and offering insights into a range of tools. It highlights the importance of remaining reflexive in relation to attitudes and emotions and discusses practical methodological and ethical challenges and ways to resolve them which can be of benefit to researchers embarking on a similar journey.
The thesis also offers detailed insights on how methodologies from different fields were integrated into a whole, arguing for transparency and reflexivity about epistemological assumptions, and how underlying paradigms shift in an interdisciplinary context.
Based on the overall findings, the thesis makes a case for considering design as healing (or a designerly way of healing), highlighting implications at a systems, social and individual level. It makes an original contribution to our understanding of design, highlighting its healing character, and proposes a new way to support mental health. The participants in this study not only had increased their own wellbeing through co-designing, but were also empowered and contributed towards healing the world. Hence, the thesis argues for a unique, holistic perspective of design and mental health, recognizing the interconnectedness of the individual, social and systemic dimensions of the healing processes that are ignited
Laser Welding
Among novel techniques, laser welding is considered an adaptable and rapidly evolving method, finding innumerable applications in engineering industries. It is capable of welding narrow and impassable joints precisely, which can be operated under computer control. This chapter of the welding Handbook reviews the most recent developments in the field of laser welding, which are used for different applications. The first section provides an overview of laser welding basics and then moves on to the developments such as high-power CO2 laser welding, laser micro-welding, and solid-state laser welding technologies. The second section underlines laser welding instruments used for joining different materials such as titanium, aluminum, and magnesium alloys, ceramics, and plastics. The third section highlights the advances in innovative laser welding methods with discussions on the applications of laser welding robots to improve the modeling and simulation of this technique. Lastly, the fourth section focuses on the use of laser welding technology in various industries including aerospace, automotive, railway, etc. The present Handbook is a practical reference for scholars, engineers, and professionals using laser welding techniques or requiring an understanding of the field of laser welding technologies
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