17,165 research outputs found
Adjacent LSTM-Based Page Scheduling for Hybrid DRAM/NVM Memory Systems
Recent advances in memory technologies have led to the rapid growth of hybrid systems that combine traditional DRAM and Non Volatile Memory (NVM) technologies, as the latter provide lower cost per byte, low leakage power and larger capacities than DRAM, while they can guarantee comparable access latency. Such kind of heterogeneous memory systems impose new challenges in terms of page placement and migration among the alternative technologies of the heterogeneous memory system. In this paper, we present a novel approach for efficient page placement on heterogeneous DRAM/NVM systems. We design an adjacent LSTM-based approach for page placement, which strongly relies on page accesses prediction, while sharing knowledge among pages with behavioral similarity. The proposed approach leads up to 65.5% optimized performance compared to existing approaches, while achieving near-optimal results and saving 20.2% energy consumption on average. Moreover, we propose a new page replacement policy, namely clustered-LRU, achieving up to 8.1% optimized performance, compared to the default Least Recently Used (LRU) policy
Identifizierung prädiktiver und prognostischer Biomarker in unterschiedlichen Tumorkompartimenten des ösophagealen Adenokarzinoms
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
Subspecies limits based on morphometry and mitochondrial DNA genomics in a polytypic species, the common grackle, Quiscalus quiscula
Nearctic migratory songbirds have demonstrated low levels of genetic differentiation and weak phylogeographical structure in mitochondrial DNA lineages compared with resident species. The common grackle, Quiscalus quiscula, is a widespread, partially migratory, North American icterid composed of three currently recognized subspecies. In this study, mensural characters (external and skeletal measurements) and the complete mitochondrial genome together with two mitochondrial genes, Cytb and ND2, were used to investigate subspecific differentiation and demographic history of the common grackle. The results showed substantial variation in body size among subspecies, mostly distributed between the ‘Florida grackle’, Quiscalus quiscula quiscula, and the two other subspecies. Analysis of mitochondrial DNA indicated low levels of genetic variation, but we found distinct haplotypes in Florida that form a clade in the phylogenetic tree. This suggests that the nominate subspecies in Florida is a distinct evolutionary unit. The sharing of haplotypes among the other subspecies (Quiscalus quiscula versicolor and Quiscalus quiscula stonei) in the north suggests high levels of gene flow, making the status of these two subspecies equivocal. Gene f low between nominate Q. q. quiscula, Q. q. versicolor and putative Q. q. stonei is probably attributable to historical changes in distribution and abundance following climate change events. We therefore recognize only two subspecies in the common grackle complex
Fair Assortment Planning
Many online platforms, ranging from online retail stores to social media
platforms, employ algorithms to optimize their offered assortment of items
(e.g., products and contents). These algorithms tend to prioritize the
platforms' short-term goals by solely featuring items with the highest
popularity or revenue. However, this practice can then lead to undesirable
outcomes for the rest of the items, making them leave the platform, and in turn
hurting the platform's long-term goals. Motivated by that, we introduce and
study a fair assortment planning problem, which requires any two items with
similar quality/merits to be offered similar outcomes. We show that the problem
can be formulated as a linear program (LP), called (FAIR), that optimizes over
the distribution of all feasible assortments. To find a near-optimal solution
to (FAIR), we propose a framework based on the Ellipsoid method, which requires
a polynomial-time separation oracle to the dual of the LP. We show that finding
an optimal separation oracle to the dual problem is an NP-complete problem, and
hence we propose a series of approximate separation oracles, which then result
in a -approx. algorithm and a PTAS for the original Problem (FAIR). The
approximate separation oracles are designed by (i) showing the separation
oracle to the dual of the LP is equivalent to solving an infinite series of
parameterized knapsack problems, and (ii) taking advantage of the structure of
the parameterized knapsack problems. Finally, we conduct a case study using the
MovieLens dataset, which demonstrates the efficacy of our algorithms and
further sheds light on the price of fairness.Comment: 86 pages, 7 figure
Hurdles and signposts on the road to virtual control groups—A case study illustrating the influence of anesthesia protocols on electrolyte levels in rats
Introduction: Virtual Control Groups (VCGs) represent the concept of using historical control data from legacy animal studies to replace concurrent control group (CCG) animals. Based on the data curation and sharing activities of the Innovative Medicine Initiatives project eTRANSAFE (enhancing TRANSlational SAFEty Assessment through Integrative Knowledge Management) the ViCoG working group was established with the objectives of i) collecting suitable historical control data sets from preclinical toxicity studies, ii) evaluating statistical methodologies for building adequate and regulatory acceptable VCGs from historical control data, and iii) sharing those control-group data across multiple pharmaceutical companies. During the qualification process of VCGs a particular focus was put on the identification of hidden confounders in the data sets, which might impair the adequate matching of VCGs with the CCG.Methods: During our analyses we identified such a hidden confounder, namely, the choice of the anesthetic procedure used in animal experiments before blood withdrawal. Anesthesia using CO2 may elevate the levels of some electrolytes such as calcium in blood, while the use of isoflurane is known to lower these values. Identification of such hidden confounders is particularly important if the underlying experimental information (e.g., on the anesthetic procedure) is not routinely recorded in the standard raw data files, such as SEND (Standard for Exchange of Non-clinical Data). We therefore analyzed how the replacement of CCGs with VCGs would affect the reproducibility of treatment-related findings regarding electrolyte values (potassium, calcium, sodium, and phosphate). The analyses were performed using a legacy rat systemic toxicity study consisting of a control and three treatment groups conducted according to pertinent OECD guidelines. In the report of this study treatment-related hypercalcemia was reported. The rats in this study were anesthetized with isoflurane.Results: Replacing the CCGs with VCGs derived from studies comprising both anesthetics resulted in a shift of control electrolyte parameters. Instead of the originally reported hypercalcemia the use of VCG led to fallacious conclusions of no observed effect or hypocalcemia.Discussion: Our study highlights the importance of a rigorous statistical analysis including the detection and elimination of hidden confounders prior to the implementation of the VCG concept
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The Epidemiology and Genetic Architecture of Vitamin D Deficiency in African Children
Vitamin D deficiency is a common public health problem worldwide. However, little is known about the epidemiology of vitamin D deficiency in Africa. In this thesis, I aimed to determine: 1) the prevalence of and risk factors associated with vitamin D deficiency in studies conducted in Africa; 2) the prevalence and predictors of vitamin D deficiency in African children; 3) the association between vitamin D and iron deficiency in African children; and 4) genetic variants that influence vitamin D status in Africans.
In a systematic review and meta-analyses of previous vitamin D studies in Africa, the average prevalence of low vitamin D status was 18.5%, 34.2% and 59.5% using cut-offs of 25-hydroxyvitamin D (25(OH)D) levels of <30 nmol/L, <50 nmol/L and <75 nmol/L, respectively. Populations at risk of vitamin D deficiency included newborns, women, and people living in high latitudes or urban areas.
In an epidemiological study of young children living in Africa, the prevalence of low vitamin D status was 0.6%, 7.8% and 44.5% using cut-offs of 25(OH)D levels of GC2 variant of the group-specific component (GC) gene, which encodes vitamin D binding protein.
Vitamin D deficiency was also associated with 80% higher odds of iron deficiency in these children. Adjusted regression models revealed that vitamin D deficiency was associated with higher ferritin and hepcidin levels suggesting lower iron status, and reduced sTfR and transferrin levels and increased TSAT and serum iron levels suggesting improved iron status.
Genome-wide association study (GWAS) in Africans revealed genetic variants that influence vitamin D status in vitamin D metabolism genes: DHCR7/NADSYN1, CYP2R1 and GC. However, the majority of SNPs from previous European GWASs did not replicate in the current GWAS.
Findings from this thesis indicate that vitamin D deficiency is prevalent in many African populations and should be considered in public health strategies in Africa
ENHANCING STUDENT ENGAGEMENT, TEACHER SELF-EFFICACY, AND PRINCIPAL LEADERSHIP SKILLS THROUGH MORNING MEETING IN AN ONLINE LEARNING ENVIRONMENT
This study examined the experiences of educators in a small, rural elementary school who provided live instruction in an online setting during the COVID-19 pandemic. The scholarly practitioner collaborated with inquiry partners to enhance student engagement, teacher self-efficacy, and principal leadership skills by implementing Morning Meeting, a social and emotional learning program from Responsive Classroom®, when students participated in remote online learning. The scholarly practitioner used over four decades of research about efficacy and identified leadership strategies and approaches that assisted in building individual and collective teacher efficacy so that teachers could effectively engage students.
Behavioral, emotional, and cognitive engagement were identified in research and used by teachers to determine the quality of participation in Morning Meeting. Teachers took daily and weekly attendance to measure engagement, and the scholarly practitioner facilitated team meetings with groups of teachers to compile comments and statements regarding student engagement. These statements were coded using pre-selected codes based on research about types of student engagement.
The scholarly practitioner facilitated the administration of a pre-study and post-study Teacher Self-Efficacy Scale so that individual, grade-span, and full-school efficacy data could be compiled. In addition, the scholarly practitioner held team meetings with the teachers to compile comments and categorize those statements into four areas: job accomplishment, skill development, social interaction, and coping with job stress. These four areas were also coded using the four categories described on the Teacher Self-Efficacy Scale.
The scholarly practitioner also maintained a journal using a self-reflection tool about the lived experiences before, during, and after the study. The emphasis on this journal was about the development and growth of leadership skills, and the categories were pre-coded using Bernard Bass’s categories of transformational leadership: individualized consideration, inspirational motivation, idealized influence, and intellectual stimulation.
Student engagement increased throughout the study, and 77 percent of students were fully engaged during the study. Teachers expressed an increase in collective efficacy at the conclusion of the study, and six of the eight teachers reported individual increases in efficacy. The scholarly practitioner’s use of differentiation within the context of transformational leadership was observed most frequently in the study
Learning disentangled speech representations
A variety of informational factors are contained within the speech signal and a single short recording of speech reveals much more than the spoken words. The best method to extract and represent informational factors from the speech signal ultimately depends on which informational factors are desired and how they will be used. In addition, sometimes methods will capture more than one informational factor at the same time such as speaker identity, spoken content, and speaker prosody.
The goal of this dissertation is to explore different ways to deconstruct the speech signal into abstract representations that can be learned and later reused in various speech technology tasks. This task of deconstructing, also known as disentanglement, is a form of distributed representation learning. As a general approach to disentanglement, there are some guiding principles that elaborate what a learned representation should contain as well as how it should function. In particular, learned representations should contain all of the requisite information in a more compact manner, be interpretable, remove nuisance factors of irrelevant information, be useful in downstream tasks, and independent of the task at hand. The learned representations should also be able to answer counter-factual questions.
In some cases, learned speech representations can be re-assembled in different ways according to the requirements of downstream applications. For example, in a voice conversion task, the speech content is retained while the speaker identity is changed. And in a content-privacy task, some targeted content may be concealed without affecting how surrounding words sound. While there is no single-best method to disentangle all types of factors, some end-to-end approaches demonstrate a promising degree of generalization to diverse speech tasks.
This thesis explores a variety of use-cases for disentangled representations including phone recognition, speaker diarization, linguistic code-switching, voice conversion, and content-based privacy masking. Speech representations can also be utilised for automatically assessing the quality and authenticity of speech, such as automatic MOS ratings or detecting deep fakes. The meaning of the term "disentanglement" is not well defined in previous work, and it has acquired several meanings depending on the domain (e.g. image vs. speech). Sometimes the term "disentanglement" is used interchangeably with the term "factorization". This thesis proposes that disentanglement of speech is distinct, and offers a viewpoint of disentanglement that can be considered both theoretically and practically
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
INVESTIGATING THE PERCEPTION OF EXPATRIATES TOWARDS IMMIGRATION SERVICE QUALITY IN SHARJAH, UNITED ARAB EMIRATES THROUGH MIXED METHOD APPROACH
The public sectors in UAE are under immense pressure to demonstrate that their services are customer-focused and that continuous performance improvement is being delivered. The United Arab Emirates is a favoured destination for expatriates due to its own citizens form a minority of the population and are barely represented in the private sector workforce. These highly unusual demographics confer high importance on the national immigration services. Recently, increased interest in international migration, specifically within the United Arab Emirates, has been shown both by government agencies and by the governments of industrialised countries. Given the importance of the expatriate labour force to economic stability and growth in the Emirates, this research investigates how immigration services are perceived, with the aim of contributing to their improvement, thus ultimately supporting economic growth. It proposes a service quality perception framework to improve understanding within SID of how to raise levels of service delivered to migrants and other persons directly or indirectly affected by SID services.
Qualitative data were collected by means of semi-structured interviews and quantitative data by means of a questionnaire survey based on the abovementioned framework. The survey data, on the variables influencing participants’ experiences and perceptions of SID services, were subjected to statistical analysis. The framework was then used to evaluate quality of service in terms of general impressions, delivery, location, response, SID culture and behaviour. Numerical data were analysed using inferential and descriptive statistics. It was found that service quality positively influenced service behaviour and that this relationship was mediated by SID culture.
This research makes an original contribution to knowledge as one of the few studies of immigration to the United Arab Emirates. By examining the workings of one immigration department, it adds to the literature on immigration departments and organisational development in developing countries. It illuminates the mechanics of immigration services and demonstrates their increasing importance to the world economy
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