Adaptive Multimedia Content Delivery for Scalable Web Servers

The phenomenal growth in the use of the World Wide Web often places a heavy load on networks and servers, threatening to increase Web server response time and raising scalability issues for both the network and the server. With the advances in the field of optical networking and the increasing use of broadband technologies like cable modems and DSL, the server and not the network, is more likely to be the bottleneck. Many clients are willing to receive a degraded, less resource intensive version of the requested content as an alternative to connection failures. In this thesis, we present an adaptive content delivery system that transparently switches content depending on the load on the server in order to serve more clients. Our system is designed to work for dynamic Web pages and streaming multimedia traffic, which are not currently supported by other adaptive content approaches. We have designed a system which is capable of quantifying the load on the server and then performing the necessary adaptation. We designed a streaming MPEG server and client which can react to the server load by scaling the quality of frames transmitted. The main benefits of our approach include: transparent content switching for content adaptation, alleviating server load by a graceful degradation of server performance and no requirement of modification to existing server software, browsers or the HTTP protocol. We experimentally evaluate our adaptive server system and compare it with an unadaptive server. We find that adaptive content delivery can support as much as 25% more static requests, 15% more dynamic requests and twice as many multimedia requests as a non-adaptive server. Our, client-side experiments performed on the Internet show that the response time savings from our system are quite significant

Unveiling the Incipient Caries by Quantitative Light-induced Fluorescence

Dental caries is one of the most prevalent chronic diseases of humans worldwide. When different stages of the disease are taken into account, from the initial to the clinically manifesting lesion, very few individuals are truly unaffected. Quantitative light-induced fluorescence (QLF) is a prominent diagnostic technique in dentistry. The purpose of this article is to review the effectiveness of QLF system in early detection of carious lesions as well as its future clinical application in dentistry. The review article has been prepared doing a literature review from the world wide web and PubMed/medline

Application of multivariate data analysis in the monitoring and control of mammalian cell processes

High throughput (HT) methodologies are increasingly being adopted for bioprocess development activities. However, often the large quantities of data generated from such studies as well as from historical batch records are not fully harnessed for their potential insights. Multivariate data analysis (MVDA) is a well-known technique that can reduce the dimensionality of large data sets and help generate useful correlations of typical process behaviour and determine root causes of process deviations. This work focuses on the application of various MVDA techniques and data mining tools to investigate the impact of process variations on the critical quality attributes (CQAs) of mammalian cell processes. Three separate projects investigating the application of these techniques were explored. The first focuses on understanding the impact of cell culture operation, generation number and initial conditions on final titre and impurity levels. A systematic methodology was applied to analyse HT data generated in a Design of Experiment (DOE) study using the ambr® 48 (advanced micro-bioreactor) system. The project applied multiple MVDA techniques including Principle Component Analysis (PCA) and Partial Least Squares (PLS) to successfully identify the key critical process measurements impacting on the target antibody concentration and host cell protein (HCP) levels at harvest. A similar approach was adopted in the second project that investigated the influence of manufacturing beyond standard operating conditions on the product-related CQAs of a mammalian cell process. The insights from the MVDA allowed the modification of the control limits of key process parameters to be redefined with confidence. The final project focuses on the development of an advanced glucose control strategy for a high titre mammalian cell line. The project aims to predict the on-line glucose concentration through correlations developed between the available on-line process measurements and the off-line metabolic profiles. The predicted glucose concentration is then used to manipulate the substrate feed rate to control the glucose concentration at a desired set-point. Better control of the glucose concentration aims to further increase titre production as well as potentially reducing unwanted post-translation modifications (PTMs) in susceptible cell lines. These techniques can be combined with the application of Process Analytical Technologies (PAT) and Quality by Design (QbD) allowing for the development of more efficient and better controlled processes

Multivariate data analysis enabling improved clone selection

Selecting a single cell from a heterogeneous transfection pool that will scale-up appropriately from a micro-scale system to a commercial facility is a challenging and hugely important task. This clonal cell line needs to demonstrate the desired product quality attributes and ensure manufacturability throughout the entire drug manufacturing lifecycle. This process typically requires 6 to 12 months and is a time, capital and labour intensive process. High throughput (HT) methodologies are increasingly being adopted to speed up this cell line selection protocol. However, often the large quantities of data generated in combination with the increase in availability of analytics results in a daunting multivariate data analysis problem. Typically, the cell line selection strategy focuses on quality attributes recorded at point of harvest such as final concentrations of process parameters including titre and viable cell density, level of aggregates or addition product quality attributes. Time-series data such as dissolved oxygen, pH or gas flow rates are often overlooked due to challenges with visualization and interpretation of the large number of process variables recorded. This work describes a novel method that implements advanced multivariate tools including principal component analysis (PCA) to better leverage the available data to help guide this challenging decision making process. The inclusion of additional process variables was demonstrated to enhance the selection of a high-yielding mammalian cell line through inclusion of scale-up dependent process parameters related to high oxygen demands and varying nutrient uptake rates. Furthermore, this technique was demonstrated to highlight problematic product heterogeneities of parent clones that were not identified through univariate analysis of the multiple cell lines. The inclusion of this MVDA methodology demonstrated a more efficient and better decision-making protocol compared to conventional cell line selection processes

Effect of nano-size on magnetostriction of BiFeO3 and exceptional magnetoelectric coupling properties of BiFeO3_P(VDF-TrFE) polymer composite films for magnetic field sensor application

The existence of magnetostriction in bulk BiFeO3 is still a matter of investigation and it is also an issue to investigate the magnetostriction effect in nano BiFeO3. Present work demonstrates the existence of magnetostrictive strain in superparamagnetic BiFeO3 nanoparticles at room temperature and the magnetoelectric coupling properties in composite form with P(VDFTrFE). Despite few reports on the magnetostriction effect in bulk BiFeO3 evidenced by the indirect method, the direct method (strain gauge) was employed in this work to examine the magnetostriction of superparamagnetic BiFeO3. In addition, a high magnetoelectric coupling coefficient was observed by the lock-in technique for optimized BiFeO3_P(VDF-TrFE) nanocomposite film. These nanocomposite films also exhibit room-temperature multiferroic properties. These results provide aspects of material with immense potential for practical applications in spintronics and magneto-electronics applications. We report a magnetoelectric sensor using superparamagnetic BiFeO3_P(VDF-TrFE) nanocomposite film for detection of ac magnetic field

Enhancing the Functionality of a Microscale Bioreactor System as an Industrial Process Development Tool for Mammalian Perfusion Culture

Without a scale-down model for perfusion, high resource demand makes cell line screening or process development challenging; therefore potentially successful cell lines or perfusion processes are unrealised and their ability untapped. We present here the re-functioning of a high capacity microscale system that is typically employed in fed-batch process development to allow perfusion operation utilising in situ gravity settling and automated sampling. In this low resource setting, which involved routine perturbations in mixing, pH and dissolved oxygen concentrations, the specific productivity and the maximum cell concentration were higher than 3.0x106 mg/cell/day and 7x107 cells/ml, respectively, across replicate microscale perfusion runs conducted at one vessel volume exchange per day. A comparative analysis was conducted at bench scale with vessels operated in perfusion mode utilising a cell retention device. Neither specific productivity nor product quality indicated by product aggregation [6%] was significantly different across scales 19 days post inoculation, thus demonstrating this setup to be a suitable and reliable platform for evaluating the performance of cell lines and the effect of process parameters relevant to perfusion mode of culturing

Jais and Jais-chat: Arabic-Centric Foundation and Instruction-Tuned Open Generative Large Language Models

We introduce Jais and Jais-chat, new state-of-the-art Arabic-centric foundation and instruction-tuned open generative large language models (LLMs). The models are based on the GPT-3 decoder-only architecture and are pretrained on a mixture of Arabic and English texts, including source code in various programming languages. With 13 billion parameters, they demonstrate better knowledge and reasoning capabilities in Arabic than any existing open Arabic and multilingual models by a sizable margin, based on extensive evaluation. Moreover, the models are competitive in English compared to English-centric open models of similar size, despite being trained on much less English data. We provide a detailed description of the training, the tuning, the safety alignment, and the evaluation of the models. We release two open versions of the model -- the foundation Jais model, and an instruction-tuned Jais-chat variant -- with the aim of promoting research on Arabic LLMs. Available at https://huggingface.co/inception-mbzuai/jais-13b-chatComment: Arabic-centric, foundation model, large-language model, LLM, generative model, instruction-tuned, Jais, Jais-cha

Impact of district mental health care plans on symptom severity and functioning of patients with priority mental health conditions: the Programme for Improving Mental Health Care (PRIME) cohort protocol

Background: The Programme for Improving Mental Health Care (PRIME) sought to implement mental health care plans (MHCP) for four priority mental disorders (depression, alcohol use disorder, psychosis and epilepsy) into routine primary care in five low- and middle-income country districts. The impact of the MHCPs on disability was evaluated through establishment of priority disorder treatment cohorts. This paper describes the methodology of these PRIME cohorts. Methods: One cohort for each disorder was recruited across some or all five districts: Sodo (Ethiopia), Sehore (India) , Chitwan (Nepal), Dr. Kenneth Kaunda (South Africa) and Kamuli (Uganda), comprising 17 treatment cohorts in total (N = 2182). Participants were adults residing in the districts who were eligible to receive mental health treatment according to primary health care staff, trained by PRIME facilitators as per the district MHCP. Patients who screened positive for depression or AUD and who were not given a diagnosis by their clinicians (N = 709) were also recruited into comparison cohorts in Ethiopia, India, Nepal and South Africa. Caregivers of patients with epilepsy or psychosis were also recruited (N = 953), together with or on behalf of the person with a mental disorder, depending on the district. The target sample size was 200 (depression and AUD), or 150 (psychosis and epilepsy) patients initiating treatment in each recruiting district. Data collection activities were conducted by PRIME research teams. Participants completed follow-up assessments after 3 months (AUD and depression) or 6 months (psychosis and epilepsy), and after 12 months. Primary outcomes were impaired functioning, using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and symptom severity, assessed using the Patient Health Questionnaire (depression), the Alcohol Use Disorder Identification Test (AUD), and number of seizures (epilepsy). Discussion: Cohort recruitment was a function of the clinical detection rate by primary health care staff, and did not meet all planned targets. The cross-country methodology reflected the pragmatic nature of the PRIME cohorts: while the heterogeneity in methods of recruitment was a consequence of differences in health systems and MHCPs, the use of the WHODAS as primary outcome measure will allow for comparison of functioning recovery across sites and disorders

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury