30 research outputs found
Innovative approaches to the use of nanotools for creating tendon tissue-mimetic constructs and disease models
No full textTese de doutoramento em Engenharia de Tecidos, Medicina Regenerativa e Células EstaminaisThe intricate composition and architecture of living tissues determine their functionality, resulting from the complex interplay between cells and the extracellular matrix (ECM). Properly addressing these characteristics is crucial for the development of 3D in vitro advanced platforms that have the potential to enhance the efficacy of knowledge-based therapy development, while significantly reducing the need for animal experimentation. This Thesis aimed at addressing specific research challenges for the development of effective tendon-mimetic constructs for tissue regeneration and disease modeling. These challenges include i) recreating the complex hierarchical and fibrillar architecture of tendon extracellular matrix; ii) the ability to remotely actuate mechanotransduction mechanisms in tissue engineered construct; iii) delivering biochemical cues involved in tendon tissue development and healing and iv) incorporating multiple cell types to replicate the complex biological processes that occur in native tissue. To address these challenges, we used state-of-the-art technologies such as 3D bioprinting and organ-on-chip technology and biomaterials, in particular nanoparticles, with unique (bio) functional properties. Building on these concepts, In the first experimental chapter (Chapter 3), cellulose nanocrystals (CNCs) surface charge chemistry was exploited to induce their ion-mediated self-assembly to recreate the unique biophysical cues provided by native tissue fibrillar Extracellular Matrix (ECMs) while allowing the design of embedded bioengineered constructs with arbitrary geometries. This system was further explored in Chapter 4, by combining magnetically- and matrix assisted 3D bioprinting for creating anisotropic microstructures. The topographical and biochemical cues of this biomimetic microstructure were combined with its magneto-mechanical stimulation during in vitro maturation, to boost stem cells mechanosignaling and to promote their commitment toward tenogenic lineage. Resourcing zinc-doped iron oxide magnetic nanoparticles incorporated into electrospun fibers (sMRF) specifically designed for this purpose. In Chapter 5 sMRF served as inspiration for developing a compartmentalized tendon-on-chip (3D-TenoC) model to study crosstalk and biochemical signaling in tendon physiology and pathophysiology. This 3D-TenoC model faithfully recreated essential characteristics of human tendons, including anisotropy and spatiotemporal distribution of cells. Overall, this thesis showcases that by combining specific bionanomaterials and advanced 3D bioprinting technologies for the construction of 3D models with an unprecedented ability to mimic native tendon tissue ECM anisotropy, physical stimulus, and customizable biochemical cues, while accommodating multiple cell types. These strategies have the potential to play a significant role in generating valuable biological data and integrating ongoing advancements in tendon tissue engineering.A intrincada composição e arquitetura dos tecidos vivos determinam sua funcionalidade, resultante
da complexa interação entre as células e a matriz extracelular (ECM). A abordagem adequada dessas
características é crucial para o desenvolvimento de plataformas 3D in vitro avançadas que têm o potencial
de aumentar a eficácia do desenvolvimento de terapias baseadas em conhecimento, contribuído em
simultâneo para reduzir significativamente a necessidade de experimentação animal. Esta Tese focou-se em
desafios de investigação específicos para o desenvolvimento de construções miméticas de tendão eficazes
para regeneração deste tecido e modelação in vitro das suas patologias. Esses desafios incluem i) recriar a
complexa arquitetura fibrilar hierárquica da matriz extracelular do tendão; ii) incorporar a capacidade de
acionar remotamente mecanismos de mecanotransdução nas construções produzidas por engenharia de
tecidos; iii) incorporar sinais bioquímicos envolvidos no desenvolvimento e cicatrização do tecido do tendão;
e iv) incorporar diferentes tipos de células de forma a replicar os processos biológicos complexos que ocorrem
no tecido nativo. Para enfrentar esses desafios, usamos tecnologias de ponta, como bioimpressão 3D e
tecnologia organ-on-chip, e biomateriais, em particular nanopartículas, com (bio)funcionalidades únicas. Com
base nesses conceitos, no primeiro capítulo experimental (Capítulo 3), a química de superfície de nanocristais
de celulose (CNCs) foi explorada para induzir a sua automontagem mediada por iões, permitindo
simultaneamente recriar os sinais biofísicos únicos providenciados pela ECM fibrilar de tecido nativo e o
design de construções de bioengenharia com geometrias arbitrárias. Este sistema foi depois explorado no
Capítulo 4, no qual a bioimpressão 3D assistida por sistemas magnéticos e matriz de suporte foi explorada
para criar microestruturas anisotrópicas. Os sinais topográficos e bioquímicos desta microestrutura
biomimética foram combinados com estimulação magneto-mecânica durante sua a maturação in vitro para
acionar a mecanosinalização de células estaminais e promover seu o seu direcionamento para a linhagem
tenogénica. Recorrendo a nanopartículas magnéticas de óxido de ferro dopadas com zinco incorporadas em
fibras electrofiadas (sMRF) especificamente concebidas para o efeito, no Capítulo 5, as sMRF serviram de
inspiração para o desenvolvimento de um modelo de tendão-em-chip compartimentado (3D-TenoC) para
estudar a comunicação e sinalização bioquímica que ocorre na fisiologia e patofisiologia do tendão. Este 3D TenoC permitiu recriar características essenciais dos tendões humanos, incluindo anisotropia e distribuição
espácio-temporal das suas células. No geral, esta tese demostra como bionanomateriais específicos e
tecnologias de bioimpressão 3D podem ser combinados para contruir modelos 3D com capacidade impar
de recriar a anisotropia da ECM do tendão nativo, providenciar estímulos físico e sinais bioquímicos
personalizáveis, e acomodar simultaneamente vários tipos de células. Estas estratégias demostram potencial
para desempenhar um papel relevante na geração de dados biológicos valiosos assim como para integrarem
avanços em continuo desenvolvimento na engenharia de tecidos de tendão.Fundação para a Ciência e a Tecnologia (FCT) - PD/BD/129403/201
3D Bioprinting for Tissue and Organ Fabrication
Get PDFThe field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development.United States. Office of Naval Research. Young Investigator ProgramNational Institutes of Health (U.S.) (Grants EB012597, AR057837, DE021468, HL099073 and R56AI105024)Presidential Early Career Award for Scientists and Engineer
Pakistan Internal Security Dilemma: Strategic Dimension
No full textThe paper reflects on Pakistan's complex security situation and the causes of current challenges that Pakistan is facing due to vacillating foreign policies. It also reviews the role of factors that contributed towards the instability of the country. After Soviet invasion of Afghanistan, Pakistan involved in a proxy war and trained Mujahideen to liberate Afghanistan. In 1980's sectarianism floored the state, and since it has rooted in Pakistani society. The country brokered several Post-Soviet peace agreements between different militaristic groups in Afghanistan but in vain. Finally, it recognized Taliban for the cause of peace (though temporary) on its Western border. After 9/11 the country had to reluctantly take a "U" turn on its Afghan policy under immense US pressure. This swing of policy opened a Pandora-box for the country i.e. terrorism, Jihadist, ethnicity, sectarianism, economic and political instability in Pakistan. In this state of affairs corruption, deteriorating law and order situation, political instability and economic fragility, variables of internal security, act as key factors in a peaceful solution of conflicts
The rise of the Taliban to the government in Afghanistan: assessment of internal and external factors
Get PDFThe arrival of the Taliban in August 2021 has significantly affected Afghanistan’s governance, particularly in terms of service delivery for the betterment of the community at large and engaging stakeholders from different institutions in the decision-making process. This paper aims to analyse the governance of the Taliban, their role and policies towards internal and external factors, including regional relations and bilateral trade with China and Central Asia, geo-strategic significance, the role of public administration and women\u27s rights in Afghanistan. Data was collected from 27 people, including government officials and common people. Snowball and purposive sampling techniques are used for research. The framework for the study is Braun and Clarke, which is for thematic analysis in six phases. Major themes from the survey highlighted that the Taliban’s goal is to establish peace and smooth administrative running of its institutions. The key stakeholders, including academics, policymakers, and individuals interested in Afghan governance and international relations, play a crucial role in the issue of Afghanistan as a country and society. They have realised that the internal ethnic strife and external forces are considerable factors contributing to the destruction of Afghan society. These stakeholders are actively working for peace and stability in the country
Online Machine Learning for Graph Topology Identification from Multiple Time Series
Get PDFHigh dimensional time series data are observed in many complex systems. In networked data, some of the time series are influenced by other time series. Identifying these relations encoded in a graph structure or topology among the time series is of paramount interest in certain applications since the identified structure can provide insights about the underlying system and can assist in inference tasks. In practice, the underlying topology is usually sparse, that is, not all the participating time series in influence each other. The goal of this dissertation pertains to study the problem of sparse topology identification under various settings.
Topology identification from time series is a challenging task. The first major challenge in topology identification is that the assumption of static topology does not hold always in practice since most of the practical systems are evolving with time. For instance, in econometrics, social networks, etc., the relations among the time series can change over time. Identifying the topologies of such dynamic networks is a major challenge.
The second major challenge is that in most practical scenarios, the data is not available at once - it is coming in a streaming fashion. Hence, batch approaches are either not applicable or they become computationally expensive since a batch algorithm is needed to be run when a new datum becomes available.
The third challenge is that the multi-dimensional time series data can contain missing values due faulty sensors, privacy and security reasons, or due to saving energy.
We address the aforementioned challenges in this dissertation by proposing online/-batch algorithms to solve the problem of time-varying topology identification. A model based on vector autoregressive (VAR) process is adopted initially. The parameters of the VAR model reveal the topology of the underlying network. First, two online algorithms are proposed for the case of streaming data. Next, using the same VAR model, two online algorithms under the framework of online optimization are presented to track the time-varying topologies. To evaluate the performance of propose online algorithms, we show that both the proposed algorithms incur a sublinear static regret. To characterize the performance theoretically in time-varying scenarios, a bound on the dynamic regret for one of the proposed algorithms (TIRSO) is derived. Next, using a structural equation model (SEM) for topology identification, an online algorithm for tracking time-varying topologies is proposed, and a bound on the dynamic regret is also derived for the proposed algorithm. Moreover, using a non-stationary VAR model, an algorithm for dynamic topology identification and breakpoint detection is also proposed, where the notion of local structural breakpoint is introduced to accommodate the concept of breakpoint where instead of the whole topology, only a few edges vary. Finally, the problem of tracking VAR-based time-varying topologies with missing data is investigated. Online algorithms are proposed where the joint signal and topology estimation is carried out. Dynamic regret analysis is also presented for the proposed algorithm. For all the previously mentioned works, simulation tests about the proposed algorithms are also presented and discussed in this dissertation. The numerical results of the proposed algorithms corroborate with the theoretical analysis presented in this dissertation
The tendon microenvironment: engineered in vitro models to study cellular crosstalk
Get PDFTendinopathy is a multi-faceted pathology characterized by alterations in tendon microstructure, cellularity and collagen composition. Challenged by the possibility of regenerating pathological or ruptured tendons, the healing mechanisms of this tissue have been widely researched over the past decades. However, so far, most of the cellular players and processes influencing tendon repair remain unknown, which emphasizes the need for developing relevant in vitro models enabling to study the complex multicellular crosstalk occurring in tendon microenvironments. In this review, we critically discuss the insights on the interaction between tenocytes and the other tendon resident cells that have been devised through different types of existing in vitro models. Building on the generated knowledge, we stress the need for advanced models able to mimic the hierarchical architecture, cellularity and physiological signaling of tendon niche under dynamic culture conditions, along with the recreation of the integrated gradients of its tissue interfaces. In a forward-looking vision of the field, we discuss how the convergence of multiple bioengineering technologies can be leveraged as potential platforms to develop the next generation of relevant in vitro models that can contribute for a deeper fundamental knowledge to develop more effective treatments.The authors acknowledge the European Union’s Horizon 2020
research and innovation program under European Research Council grant agreement 772817 and Twinning grant agreement no. 810850 – Achilles. Fundação para a Ciência e a Tecnologia (FCT) for project PTDC/NAN-MAT/30595/2017 and for CEE-CIND/01375/2017 (MGF) and 2020.03410.CEECIND (RMAD). Schematics in some figures were created with BioRender.com. The authors also want to acknowledge Mahwish Bakht (3B’s Research Group, University of Minho) for designing Fig. 1
New consistency orchestrators for emerging distributed systems
Get PDFWe are gradually becoming more dependent on various distributed systems, e.g., smart home management systems, bank management, traffic monitoring, etc. Some run on data-centers while others run on edge devices, e.g., smart home applications. In all these environments, efficiently maintaining consistency across such a large number of components is a hard challenge.
Consistency ensures a coherent view across the disparate components of a distributed system. An inconsistent view might lead to various issues that directly impact user experience. For example, in a database management system, an inconsistent view of a primary replica might make the system slow, or show stale data to users. If a bank account has two primary-replicas, each of them might show their own version of the account balance -- this leads to incorrect banking transactions. Similarly, in a smart home, failing to isolate concurrent routines (sequence of commands) might end the home in a state not consistent with the user's expectation. E.g., the outcome of two concurrent routines R1 = {Turn all light ON} and R2 = {Turn all light OFF} might end up in a state where some of the lights are ON while others are OFF.
Addressing this requires the disparate components of a distributed system to have coordination. Such coordination includes maintaining a consistent view of the failed nodes, leader election, consistent primary replica selection, coherence in smart home's current state, etc. Orchestrators are dedicated entities that use specialized protocols (e.g., Chubby, ZooKeeper etc.) to help coordinate the components.
Distributed systems can use i) generic external orchestrators such as Zookeeper, Chubby etc., or 2) build their own internal orchestrator. Unlike external orchestrators, internal orchestrators avoid external dependencies and are flexible and modifiable, e.g., making it relatively easier to provide complex consistency guarantees and providing consistent and reliable distributed data-structures.
In this thesis we present new internal orchestrators for maintaining consistency in both edge-based and cloud-based distributed systems. This thesis has the following contributions: for edge-based distributed systems, we develop a smart home orchestrator called SafeHome that offers a congruent end state by guaranteeing stronger properties, e.g., Isolation, Atomicity, Safety. This is an improvement over the best-effort philosophy used in today's smart homes which leads to incongruent states. Second, For cloud-based distributed systems, we reveal and analyze Service Fabric's consistent and scalable failure detector, which is the heart of its internal orchestration mechanisms. Third, we present a new way to decentralize SF's arbitration technique and design a consistent failure detector on top of it, which offers identical consistency guaranties as SF's centralized scheme. We also provide formal proof of correctness and time-bound for both central and distributed arbitrator schemes.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2022-05-01The student, Shegufta Ahsan, accepted the attached license on 2020-05-01 at 15:22.The student, Shegufta Ahsan, submitted this Dissertation for approval on 2020-05-01 at 15:39.This Dissertation was approved for publication on 2020-05-03 at 18:48.DSpace SAF Submission Ingestion Package generated from Vireo submission #15157 on 2020-08-25 at 17:28:36Made available in DSpace on 2020-08-26T23:57:22Z (GMT). No. of bitstreams: 3
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Trust-building mechanisms in Abu Hamed al-Gharnati's travelogues based on "The Delicate of Hearts"
No full textAbu Hamed al-Gharnati has written two travelogues in the field of Arabic travel writing, entitled "The Delicate of Hearts and Elite Admiration" and "Expressed some of the Morocco’s wonders". A unique feature of both travelogues is their wonder-taking, meaning that the travel writer seeks to narrate amazing events and to focus on scenes that surprise us. For this reason, he uses the word "wonders" in the title of his travelogue. This approach of the author delays the reader and makes them consider them superstitious stories that have no real context. Ghranati, who is fascinated by the remarkable observations, realizes this and uses various mechanisms to reassure the reader and create a real world for him while dealing with strange stories. The present study intends to use the descriptive-analytical method to examine the mechanisms of building trust, their tools and goals in the travelogue of "The Delicate of Hearts". Findings indicate that these methods of building trust, along with related tools, are reflected in various ways in this travelogue, such as: A: Transmission of visual and audio content. B: Taking care in inserting their sources and narrations. C: Creating a logical atmosphere in the process of narration and anecdote. It is worth noting that in this book, there are also news and anecdotes that the author has not presented with a reliable structure and ,therefore, lack trust-building tools. The reason for this seems to be that the author seeks to gradually gain the reader's confidence in his method of citation by providing reassuring patterns. Of course, this phenomenon is faint and the distinctive style in the Gharnati’s narrative method is the use of trust building approach
Seroprevalence of toxoplasmosis and current thinking regarding screening in pregnancy: A review of the literature and case study discussion
No full textThe approach to the diagnosis and treatment of congenital toxoplasmosis has been one of flux and debate, fueled by lack of knowledge, lack of consensus, different methods of screening and different national policies for screening in different parts of the world. Countries with higher prevalence of disease such as in Europe and South America have a heightened awareness of the need to screen and treat for this parasitic infection during pregnancy. In contrast, in the United States, it is a condition scarcely discussed and has been largely ignored except in some large centers and by a few researchers. Policies and research strategies for any condition should start with obtaining good data. The aims of this thesis included a review of prevalence studies conducted in the United States, focused on the past 20 years, combined with a description of original research conducted by the author several years ago. The latter was a cross-sectional study performed in Houston, one of the largest American cities with a great ethnic mix. The study analyzed prevalence rates of Toxoplasma gondii IgG antibody in sera of women of reproductive age. Overall seroprevalence was 12.3%. In keeping with other studies, higher prevalence correlated with lower socioeconomic status, Black and Hispanic and Asian ethnicities, and increasing age. A literature search revealed only three prevalence studies performed in the United States over the past 20 years, with another four studies only referred to as personal communications or within a textbook, without further study detail available. The literature review also revealed a lack of consensus on whether or not to screen for toxoplasmosis in pregnancy, and even whether or not treatment in utero is worthwhile. Proponents of screening and treatment in pregnancy site studies both in the United States and France, emphasize that treatment reduces disease manifestations in infants. Opponents cite other studies that show only marginal benefits, together with potential side effects of medication regimens and generation of anxiety in parents. What is agreed on so far is the value of educating pregnant women on how to avoid contracting toxoplasmosis, and educating physicians on making the best use of reference laboratories before major treatment decisions are made. Further research to reevaluate the literature critically, review new treatment regimens and examine costs and benefits of screening and treatment of toxoplasmosis in pregnancy, bringing together European and American researchers, is needed
Biomodeling: Perforated and Endothelialized Elastomeric Tubes for Vascular Modeling (Adv. Mater. Technol. 9/2019)
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