13,005 research outputs found
Meso-scale FDM material layout design strategies under manufacturability constraints and fracture conditions
In the manufacturability-driven design (MDD) perspective, manufacturability of the product or system is the most important of the design requirements. In addition to being able to ensure that complex designs (e.g., topology optimization) are manufacturable with a given process or process family, MDD also helps mechanical designers to take advantage of unique process-material effects generated during manufacturing. One of the most recognizable examples of this comes from the scanning-type family of additive manufacturing (AM) processes; the most notable and familiar member of this family is the fused deposition modeling (FDM) or fused filament fabrication (FFF) process. This process works by selectively depositing uniform, approximately isotropic beads or elements of molten thermoplastic material (typically structural engineering plastics) in a series of pre-specified traces to build each layer of the part. There are many interesting 2-D and 3-D mechanical design problems that can be explored by designing the layout of these elements. The resulting structured, hierarchical material (which is both manufacturable and customized layer-by-layer within the limits of the process and material) can be defined as a manufacturing process-driven structured material (MPDSM). This dissertation explores several practical methods for designing these element layouts for 2-D and 3-D meso-scale mechanical problems, focusing ultimately on design-for-fracture. Three different fracture conditions are explored: (1) cases where a crack must be prevented or stopped, (2) cases where the crack must be encouraged or accelerated, and (3) cases where cracks must grow in a simple pre-determined pattern. Several new design tools, including a mapping method for the FDM manufacturability constraints, three major literature reviews, the collection, organization, and analysis of several large (qualitative and quantitative) multi-scale datasets on the fracture behavior of FDM-processed materials, some new experimental equipment, and the refinement of a fast and simple g-code generator based on commercially-available software, were developed and refined to support the design of MPDSMs under fracture conditions. The refined design method and rules were experimentally validated using a series of case studies (involving both design and physical testing of the designs) at the end of the dissertation. Finally, a simple design guide for practicing engineers who are not experts in advanced solid mechanics nor process-tailored materials was developed from the results of this project.U of I OnlyAuthor's request
Sensitivity analysis for ReaxFF reparameterization using the Hilbert-Schmidt independence criterion
We apply a global sensitivity method, the Hilbert-Schmidt independence
criterion (HSIC), to the reparameterization of a Zn/S/H ReaxFF force field to
identify the most appropriate parameters for reparameterization. Parameter
selection remains a challenge in this context as high dimensional optimizations
are prone to overfitting and take a long time, but selecting too few parameters
leads to poor quality force fields. We show that the HSIC correctly and quickly
identifies the most sensitive parameters, and that optimizations done using a
small number of sensitive parameters outperform those done using a higher
dimensional reasonable-user parameter selection. Optimizations using only
sensitive parameters: 1) converge faster, 2) have loss values comparable to
those found with the naive selection, 3) have similar accuracy in validation
tests, and 4) do not suffer from problems of overfitting. We demonstrate that
an HSIC global sensitivity is a cheap optimization pre-processing step that has
both qualitative and quantitative benefits which can substantially simplify and
speedup ReaxFF reparameterizations.Comment: author accepted manuscrip
Composing games into complex institutions
Game theory is used by all behavioral sciences, but its development has long
centered around tools for relatively simple games and toy systems, such as the
economic interpretation of equilibrium outcomes. Our contribution,
compositional game theory, permits another approach of equally general appeal:
the high-level design of large games for expressing complex architectures and
representing real-world institutions faithfully. Compositional game theory,
grounded in the mathematics underlying programming languages, and introduced
here as a general computational framework, increases the parsimony of game
representations with abstraction and modularity, accelerates search and design,
and helps theorists across disciplines express real-world institutional
complexity in well-defined ways. Relative to existing approaches in game
theory, compositional game theory is especially promising for solving game
systems with long-range dependencies, for comparing large numbers of
structurally related games, and for nesting games into the larger logical or
strategic flows typical of real world policy or institutional systems.Comment: ~4000 words, 6 figure
Annual SHOT Report 2018
SHOT is affiliated to the Royal College of PathologistsAll NHS organisations must move away from a blame culture towards a just and learning culture. All clinical and laboratory staff should be encouraged to become familiar with human factors and ergonomics concepts. All transfusion decisions must be made after carefully assessing the risks and benefits of transfusion therapy. Collaboration and co-ordination among staff is vital
Examples of works to practice staccato technique in clarinet instrument
Klarnetin staccato tekniğini güçlendirme aşamaları eser çalışmalarıyla uygulanmıştır. Staccato
geçişlerini hızlandıracak ritim ve nüans çalışmalarına yer verilmiştir. Çalışmanın en önemli amacı
sadece staccato çalışması değil parmak-dilin eş zamanlı uyumunun hassasiyeti üzerinde de
durulmasıdır. Staccato çalışmalarını daha verimli hale getirmek için eser çalışmasının içinde etüt
çalışmasına da yer verilmiştir. Çalışmaların üzerinde titizlikle durulması staccato çalışmasının ilham
verici etkisi ile müzikal kimliğe yeni bir boyut kazandırmıştır. Sekiz özgün eser çalışmasının her
aşaması anlatılmıştır. Her aşamanın bir sonraki performans ve tekniği güçlendirmesi esas alınmıştır.
Bu çalışmada staccato tekniğinin hangi alanlarda kullanıldığı, nasıl sonuçlar elde edildiği bilgisine
yer verilmiştir. Notaların parmak ve dil uyumu ile nasıl şekilleneceği ve nasıl bir çalışma disiplini
içinde gerçekleşeceği planlanmıştır. Kamış-nota-diyafram-parmak-dil-nüans ve disiplin
kavramlarının staccato tekniğinde ayrılmaz bir bütün olduğu saptanmıştır. Araştırmada literatür
taraması yapılarak staccato ile ilgili çalışmalar taranmıştır. Tarama sonucunda klarnet tekniğin de
kullanılan staccato eser çalışmasının az olduğu tespit edilmiştir. Metot taramasında da etüt
çalışmasının daha çok olduğu saptanmıştır. Böylelikle klarnetin staccato tekniğini hızlandırma ve
güçlendirme çalışmaları sunulmuştur. Staccato etüt çalışmaları yapılırken, araya eser çalışmasının
girmesi beyni rahatlattığı ve istekliliği daha arttırdığı gözlemlenmiştir. Staccato çalışmasını yaparken
doğru bir kamış seçimi üzerinde de durulmuştur. Staccato tekniğini doğru çalışmak için doğru bir
kamışın dil hızını arttırdığı saptanmıştır. Doğru bir kamış seçimi kamıştan rahat ses çıkmasına
bağlıdır. Kamış, dil atma gücünü vermiyorsa daha doğru bir kamış seçiminin yapılması gerekliliği
vurgulanmıştır. Staccato çalışmalarında baştan sona bir eseri yorumlamak zor olabilir. Bu açıdan
çalışma, verilen müzikal nüanslara uymanın, dil atış performansını rahatlattığını ortaya koymuştur.
Gelecek nesillere edinilen bilgi ve birikimlerin aktarılması ve geliştirici olması teşvik edilmiştir.
Çıkacak eserlerin nasıl çözüleceği, staccato tekniğinin nasıl üstesinden gelinebileceği anlatılmıştır.
Staccato tekniğinin daha kısa sürede çözüme kavuşturulması amaç edinilmiştir. Parmakların
yerlerini öğrettiğimiz kadar belleğimize de çalışmaların kaydedilmesi önemlidir. Gösterilen azmin ve
sabrın sonucu olarak ortaya çıkan yapıt başarıyı daha da yukarı seviyelere çıkaracaktır
A direct-laser-written heart-on-a-chip platform for generation and stimulation of engineered heart tissues
In this dissertation, we first develop a versatile microfluidic heart-on-a-chip model to generate 3D-engineered human cardiac microtissues in highly-controlled microenvironments. The platform, which is enabled by direct laser writing (DLW), has tailor-made attachment sites for cardiac microtissues and comes with integrated strain actuators and force sensors. Application of external pressure waves to the platform results in controllable time-dependent forces on the microtissues. Conversely, oscillatory forces generated by the microtissues are transduced into measurable electrical outputs. After characterization of the responsivity of the transducers, we demonstrate the capabilities of this platform by studying the response of cardiac microtissues to prescribed mechanical loading and pacing.
Next, we tune the geometry and mechanical properties of the platform to enable parametric studies on engineered heart tissues. We explore two geometries: a rectangular seeding well with two attachment sites, and a stadium-like seeding well with six attachment sites. The attachment sites are placed symmetrically in the longitudinal direction. The former geometry promotes uniaxial contraction of the tissues; the latter additionally induces diagonal
fiber alignment. We systematically increase the length for both configurations and observe a positive correlation between fiber alignment at the center of the microtissues and tissue length. However, progressive thinning and “necking” is also observed, leading to the failure of longer tissues over time. We use the DLW technique to improve the platform, softening
the mechanical environment and optimizing the attachment sites for generation of stable microtissues at each length and geometry. Furthermore, electrical pacing is incorporated into the platform to evaluate the functional dynamics of stable microtissues over the entire range of physiological heart rates. Here, we typically observe a decrease in active force and contraction duration as a function of frequency.
Lastly, we use a more traditional ?TUG platform to demonstrate the effects of subthreshold electrical pacing on the rhythm of the spontaneously contracting cardiac microtissues. Here, we observe periodic M:N patterns, in which there are ? cycles of stimulation for every ? tissue contractions. Using electric field amplitude, pacing frequency, and homeostatic beating frequencies of the tissues, we provide an empirical map for predicting the emergence of these rhythms
Strategies for Early Learners
Welcome to learning about how to effectively plan curriculum for young children. This textbook will address: • Developing curriculum through the planning cycle • Theories that inform what we know about how children learn and the best ways for teachers to support learning • The three components of developmentally appropriate practice • Importance and value of play and intentional teaching • Different models of curriculum • Process of lesson planning (documenting planned experiences for children) • Physical, temporal, and social environments that set the stage for children’s learning • Appropriate guidance techniques to support children’s behaviors as the self-regulation abilities mature. • Planning for preschool-aged children in specific domains including o Physical development o Language and literacy o Math o Science o Creative (the visual and performing arts) o Diversity (social science and history) o Health and safety • Making children’s learning visible through documentation and assessmenthttps://scholar.utc.edu/open-textbooks/1001/thumbnail.jp
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
Embodying entrepreneurship: everyday practices, processes and routines in a technology incubator
The growing interest in the processes and practices of entrepreneurship has
been dominated by a consideration of temporality. Through a thirty-six-month
ethnography of a technology incubator, this thesis contributes to extant
understanding by exploring the effect of space. The first paper explores how
class structures from the surrounding city have appropriated entrepreneurship
within the incubator. The second paper adopts a more explicitly spatial analysis
to reveal how the use of space influences a common understanding of
entrepreneurship. The final paper looks more closely at the entrepreneurs within
the incubator and how they use visual symbols to develop their identity. Taken
together, the three papers reject the notion of entrepreneurship as a primarily
economic endeavour as articulated through commonly understood language and
propose entrepreneuring as an enigmatic attractor that is accessed through the
ambiguity of the non-verbal to develop the ‘new’. The thesis therefore contributes
to the understanding of entrepreneurship and proposes a distinct role for the non-verbal in that understanding
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