Exploiting the bimodality of speech in the cocktail party problem

The cocktail party problem is one of following a conversation in a crowded room where there are many competing sound sources, such as the voices of other speakers or music. To address this problem using computers, digital signal processing solutions commonly use blind source separation (BSS) which aims to separate all the original sources (voices) from the mixture simultaneously. Traditionally, BSS methods have relied on information derived from the mixture of sources to separate the mixture into its constituent elements. However, the human auditory system is well adapted to handle the cocktail party scenario, using both auditory and visual information to follow (or hold) a conversation in a such an environment. This thesis focuses on using visual information of the speakers in a cocktail party like scenario to aid in improving the performance of BSS. There are several useful applications of such technology, for example: a pre-processing step for a speech recognition system, teleconferencing or security surveillance. The visual information used in this thesis is derived from the speaker's mouth region, as it is the most visible component of speech production. Initial research presented in this thesis considers a joint statistical model of audio and visual features, which is used to assist in control ling the convergence behaviour of a BSS algorithm. The results of using the statistical models are compared to using the raw audio information alone and it is shown that the inclusion of visual information greatly improves its convergence behaviour. Further research focuses on using the speaker's mouth region to identify periods of time when the speaker is silent through the development of a visual voice activity detector (V-VAD) (i.e. voice activity detection using visual information alone). This information can be used in many different ways to simplify the BSS process. To this end, two novel V-VADs were developed and tested within a BSS framework, which result in significantly improved intelligibility of the separated source associated with the V-VAD output. Thus the research presented in this thesis confirms the viability of using visual information to improve solutions to the cocktail party problem.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Exploiting the bimodality of speech in the cocktail party problem

The cocktail party problem is one of following a conversation in a crowded room where there are many competing sound sources, such as the voices of other speakers or music. To address this problem using computers, digital signal processing solutions commonly use blind source separation (BSS) which aims to separate all the original sources (voices) from the mixture simultaneously. Traditionally, BSS methods have relied on information derived from the mixture of sources to separate the mixture into its constituent elements. However, the human auditory system is well adapted to handle the cocktail party scenario, using both auditory and visual information to follow (or hold) a conversation in a such an environment. This thesis focuses on using visual information of the speakers in a cocktail party like scenario to aid in improving the performance of BSS. There are several useful applications of such technology, for example: a pre-processing step for a speech recognition system, teleconferencing or security surveillance. The visual information used in this thesis is derived from the speaker's mouth region, as it is the most visible component of speech production. Initial research presented in this thesis considers a joint statistical model of audio and visual features, which is used to assist in control ling the convergence behaviour of a BSS algorithm. The results of using the statistical models are compared to using the raw audio information alone and it is shown that the inclusion of visual information greatly improves its convergence behaviour. Further research focuses on using the speaker's mouth region to identify periods of time when the speaker is silent through the development of a visual voice activity detector (V-VAD) (i.e. voice activity detection using visual information alone). This information can be used in many different ways to simplify the BSS process. To this end, two novel V-VADs were developed and tested within a BSS framework, which result in significantly improved intelligibility of the separated source associated with the V-VAD output. Thus the research presented in this thesis confirms the viability of using visual information to improve solutions to the cocktail party problem.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Reusable Container System Optimization for Smart Cities

Federal and local governments are investing in methods to discourage use of disposable containers in order to reduce waste generation and protect the environment. In this project we propose the use of reusable takeout food containers as a replacement for disposable takeout food containers. Reusable takeout container systems may use barcode or RFID (radio frequency identification) technology to track and manage the distribution, collection, cleaning, and end-of-life recycling of reusable takeout food containers. Such systems will require the use of container collection bins. The design and optimization of a network of container collection bins is the topic of this project. We propose a method to optimize the location network of collection bins at a Smart City. As a case study we use data collected in the city of San Luis Obispo, CA. The reusable container use cycle can be described as follows. A company provides the reusable takeout food containers to restaurants. The restaurants distribute these containers to their customers. After the container is used a customer drops it off in a convenient location for the company to pick it up and wash it. Since convenience of container drop off is crucial to customer participation, strategically placing the drop off bins around the city such that they are highly visible and easily accessible will maximize user satisfaction and benefit to the city. Determining the optimal set of container collection bin locations was performed using a linear programming model that optimized the bin network visibility and accessibility. Visibility and accessibility were measured by traffic volume, pedestrian volume, and population density. The optimization model included varying the quantities of drop-off bins, as well as varying bin sizes and costs. An economic analysis was used to determine the optimal combination of quantity of bins, bin size, and bin cost that maximized the benefit to the city. We simulated the potential container collection routes in order to estimate collection and transportation times and determine the optimal set of collection routes. Similar to the linear programming model, the simulation model also had variable input capabilities. The flexibility of our models may prove useful for future efforts to plan reusable container systems for Smart Cities

Exploiting the bimodality of speech in the cocktail party problem

The cocktail party problem is one of following a conversation in a crowded room where there are many competing sound sources, such as the voices of other speakers or music. To address this problem using computers, digital signal processing solutions commonly use blind source separation (BSS) which aims to separate all the original sources (voices) from the mixture simultaneously. Traditionally, BSS methods have relied on information derived from the mixture of sources to separate the mixture into its constituent elements. However, the human auditory system is well adapted to handle the cocktail party scenario, using both auditory and visual information to follow (or hold) a conversation in a such an environment. This thesis focuses on using visual information of the speakers in a cocktail party like scenario to aid in improving the performance of BSS. There are several useful applications of such technology, for example: a pre-processing step for a speech recognition system, teleconferencing or security surveillance. The visual information used in this thesis is derived from the speaker's mouth region, as it is the most visible component of speech production. Initial research presented in this thesis considers a joint statistical model of audio and visual features, which is used to assist in control ling the convergence behaviour of a BSS algorithm. The results of using the statistical models are compared to using the raw audio information alone and it is shown that the inclusion of visual information greatly improves its convergence behaviour. Further research focuses on using the speaker's mouth region to identify periods of time when the speaker is silent through the development of a visual voice activity detector (V-VAD) (i.e. voice activity detection using visual information alone). This information can be used in many different ways to simplify the BSS process. To this end, two novel V-VADs were developed and tested within a BSS framework, which result in significantly improved intelligibility of the separated source associated with the V-VAD output. Thus the research presented in this thesis confirms the viability of using visual information to improve solutions to the cocktail party problem

Convergence of a common solution to broad ebolavirus neutralization by glycan cap directed human antibodies

Antibodies that target the glycan cap epitope on ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization is not well-understood. Here we present cryo-electron microscopy (cryo-EM) structures of several glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLD) to the glycan cap, which we name the MLD-anchor and cradle. Antibodies that bind to the MLD-cradle share common features, including the use of IGHV1-69 and IGHJ6 germline genes, which exploit hydrophobic residues and form beta-hairpin structures to mimic the MLD-anchor, disrupt MLD attachment, destabilize GP quaternary structure and block cleavage events required for receptor binding. Our results collectively provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies

Lifespan extension and the doctrine of double effect

Recent developments in biogerontology—the study of the biology of ageing—suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan—a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the ‘double effect argument’, has gone unnoticed. This article exposes and critically evaluates this ‘double effect argument’. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the ‘double effect argument’ is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes