Time-Contrastive Learning Based Deep Bottleneck Features for Text-Dependent Speaker Verification

There are a number of studies about extraction of bottleneck (BN) features from deep neural networks (DNNs)trained to discriminate speakers, pass-phrases and triphone states for improving the performance of text-dependent speaker verification (TD-SV). However, a moderate success has been achieved. A recent study [1] presented a time contrastive learning (TCL) concept to explore the non-stationarity of brain signals for classification of brain states. Speech signals have similar non-stationarity property, and TCL further has the advantage of having no need for labeled data. We therefore present a TCL based BN feature extraction method. The method uniformly partitions each speech utterance in a training dataset into a predefined number of multi-frame segments. Each segment in an utterance corresponds to one class, and class labels are shared across utterances. DNNs are then trained to discriminate all speech frames among the classes to exploit the temporal structure of speech. In addition, we propose a segment-based unsupervised clustering algorithm to re-assign class labels to the segments. TD-SV experiments were conducted on the RedDots challenge database. The TCL-DNNs were trained using speech data of fixed pass-phrases that were excluded from the TD-SV evaluation set, so the learned features can be considered phrase-independent. We compare the performance of the proposed TCL bottleneck (BN) feature with those of short-time cepstral features and BN features extracted from DNNs discriminating speakers, pass-phrases, speaker+pass-phrase, as well as monophones whose labels and boundaries are generated by three different automatic speech recognition (ASR) systems. Experimental results show that the proposed TCL-BN outperforms cepstral features and speaker+pass-phrase discriminant BN features, and its performance is on par with those of ASR derived BN features. Moreover,....Comment: Copyright (c) 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other work

Vocal Tract Length Perturbation for Text-Dependent Speaker Verification with Autoregressive Prediction Coding

In this letter, we propose a vocal tract length (VTL) perturbation method for text-dependent speaker verification (TD-SV), in which a set of TD-SV systems are trained, one for each VTL factor, and score-level fusion is applied to make a final decision. Next, we explore the bottleneck (BN) feature extracted by training deep neural networks with a self-supervised objective, autoregressive predictive coding (APC), for TD-SV and compare it with the well-studied speaker-discriminant BN feature. The proposed VTL method is then applied to APC and speaker-discriminant BN features. In the end, we combine the VTL perturbation systems trained on MFCC and the two BN features in the score domain. Experiments are performed on the RedDots challenge 2016 database of TD-SV using short utterances with Gaussian mixture model-universal background model and i-vector techniques. Results show the proposed methods significantly outperform the baselines.Comment: Copyright (c) 2021 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other work

Identifying Improved Sites for Heterologous Gene Integration Using ATAC-seq

Constructing efficient cellular factories often requires integration of heterologous pathways for synthesis of novel compounds and improved cellular productivity. Few genomic sites are routinely used, however, for efficient integration and expression of heterologous genes, especially in nonmodel hosts. Here, a data-guided framework for informing suitable integration sites for heterologous genes based on ATAC-seq was developed in the nonmodel yeast Komagataella phaffii. Single-copy GFP constructs were integrated using CRISPR/Cas9 into 38 intergenic regions (IGRs) to evaluate the effects of IGR size, intensity of ATAC-seq peaks, and orientation and expression of adjacent genes. Only the intensity of accessibility peaks was observed to have a significant effect, with higher expression observed from IGRs with low- to moderate-intensity peaks than from high-intensity peaks. This effect diminished for tandem, multicopy integrations, suggesting that the additional copies of exogenous sequence buffered the transcriptional unit of the transgene against effects from endogenous sequence context. The approach developed from these results should provide a basis for nominating suitable IGRs in other eukaryotic hosts from an annotated genome and ATAC-seq data

Agave: A promising feedstock for biofuels in the water-energy-food-environment (WEFE) nexus

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe aim of this study was to conduct the first comprehensive life cycle assessment and economic analysis on ethanol produced from agave. Compositional and field data from a field experiment in Queensland, Australia was used. Our study shows that ethanol yields from agave (7414 L/ha/year) are comparable to Brazilian sugarcane (9900/L/ha/year) and higher than US corn ethanol (3800/L/ha/year). Furthermore, agave outperforms current first generation biofuel crops in water-related impacts, including Freshwater Eutrophication (96% lower than corn and 88% lower than sugarcane), Marine Ecotoxicity (59% lower than corn and 53% lower than sugarcane) and Water Consumption (46% lower than corn and 69% lower than sugarcane). The life cycle fossil energy use (Fossil Resource Scarcity) for agave is 58% lower than corn and 6% higher than sugarcane. The Global Warming impact for agave is also 62% and 30% lower than that of corn and sugarcane, respectively. Although its Land Use impact, measured by land occupied per unit ethanol output, is 98% higher than corn and 2% higher than sugarcane, agave can be grown on arid land that is not suitable for food crops. The economic analysis suggests that first generation ethanol production from agave is not commercially viable without government support. Overall, the results show that agave is promising for biofuel production in the water-energy-food-environment context.Engineering and Physical Sciences Research Council (EPSRC)Natural Environment Research Council (NERC

Non-invasive, label-free optical analysis to detect aneuploidy within the inner cell mass of the preimplantation embryo

STUDY QUESTION: Can label-free, non-invasive optical imaging by hyperspectral autofluorescence microscopy discern between euploid and aneuploid cells within the inner cell mass (ICM) of the mouse preimplantation embryo? SUMMARY ANSWER: Hyperspectral autofluorescence microscopy enables discrimination between euploid and aneuploid ICM in mouse embryos. WHAT IS KNOWN ALREADY: Euploid/aneuploid mosaicism affects up to 17.3% of human blastocyst embryos with trophectoderm biopsy or spent media currently utilized to diagnose aneuploidy and mosaicism in clinical in vitro fertilization. Based on their design, these approaches will fail to diagnose the presence or proportion of aneuploid cells within the foetal lineage ICM of some blastocyst embryos. STUDY DESIGN, SIZE, DURATION: The impact of aneuploidy on cellular autofluorescence and metabolism of primary human fibroblast cells and mouse embryos was assessed using a fluorescence microscope adapted for imaging with multiple spectral channels (hyperspectral imaging). Primary human fibroblast cells with known ploidy were subjected to hyperspectral imaging to record native cell fluorescence (4-6 independent replicates, euploid n = 467; aneuploid n = 969). For mouse embryos, blastomeres from the eight-cell stage (five independent replicates: control n = 39; reversine n = 44) and chimeric blastocysts (eight independent replicates: control n = 34; reversine n = 34; 1:1 (control:reversine) n = 30 and 1:3 (control:reversine) n = 37) were utilized for hyperspectral imaging. The ICM from control and reversine-treated embryos were mechanically dissected and their karyotype confirmed by whole genome sequencing (n = 13 euploid and n = 9 aneuploid). PARTICIPANTS/MATERIALS, SETTING, METHODS: Two models were employed: (i) primary human fibroblasts with known karyotype and (ii) a mouse model of embryo aneuploidy where mouse embryos were treated with reversine, a reversible spindle assembly checkpoint inhibitor, during the four- to eight-cell division. Individual blastomeres were dissociated from control and reversine-treated eight-cell embryos and either imaged directly or used to generate chimeric blastocysts with differing ratios of control:reversine-treated cells. Individual blastomeres and embryos were interrogated by hyperspectral imaging. Changes in cellular metabolism were determined by quantification of metabolic co-factors (inferred from their autofluorescence signature): NAD(P)H and flavins with the subsequent calculation of the optical redox ratio (ORR: flavins/[NAD(P)H + flavins]). Autofluorescence signals obtained from hyperspectral imaging were examined mathematically to extract features from each cell/blastomere/ICM. This was used to discriminate between different cell populations. MAIN RESULTS AND THE ROLE OF CHANCE: An increase in the relative abundance of NAD(P)H and decrease in flavins led to a significant reduction in the ORR for aneuploid cells in primary human fibroblasts and reversine-treated mouse blastomeres (P < 0.05). Mathematical analysis of endogenous cell autofluorescence achieved separation between (i) euploid and aneuploid primary human fibroblast cells, (ii) control and reversine-treated mouse blastomeres cells, (iii) control and reversine-treated chimeric blastocysts, (iv) 1:1 and 1:3 chimeric blastocysts and (v) confirmed euploid and aneuploid ICM from mouse blastocysts. The accuracy of these separations was supported by receiver operating characteristic curves with areas under the curve of 0.97, 0.99, 0.87, 0.88 and 0.93, respectively. We believe that the role of chance is low as mathematical features separated euploid from aneuploid in both human fibroblasts and ICM of mouse blastocysts.N/A. LIMITATIONS, REASONS FOR CAUTION: Although we were able to discriminate between euploid and aneuploid ICM in mouse blastocysts, confirmation of this approach in human embryos is required. While we show this approach is safe in mouse, further validation is required in large animal species prior to implementation in a clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: We have developed an original, accurate and non-invasive optical approach to assess aneuploidy within the ICM of mouse embryos in the absence of fluorescent tags. Hyperspectral autofluorescence imaging was able to discriminate between euploid and aneuploid human fibroblast and mouse blastocysts (ICM). This approach may potentially lead to a new diagnostic for embryo analysis. STUDY FUNDING/COMPETING INTEREST(S): K.R.D. is supported by a Mid-Career Fellowship from the Hospital Research Foundation (C-MCF-58-2019). This study was funded by the Australian Research Council Centre of Excellence for Nanoscale Biophotonics (CE140100003) and the National Health and Medical Research Council (APP2003786). The authors declare that there is no conflict of interest

Easy on that trigger dad: a study of long term family photo retrieval

We examine the effects of new technologies for digital photography on people's longer term storage and access to collections of personal photos. We report an empirical study of parents' ability to retrieve photos related to salient family events from more than a year ago. Performance was relatively poor with people failing to find almost 40% of pictures. We analyze participants' organizational and access strategies to identify reasons for this poor performance. Possible reasons for retrieval failure include: storing too many pictures, rudimentary organization, use of multiple storage systems, failure to maintain collections and participants' false beliefs about their ability to access photos. We conclude by exploring the technical and theoretical implications of these findings

Differentiating Non-Motor Symptoms in Parkinson's Disease from Controls and Hemifacial Spasm

10.1371/journal.pone.0049596PLoS ONE82

Long-term survival in a patient with progressive multifocal leukoencephalopathy after therapy with rituximab, fludarabine and cyclophosphamide for chronic lymphocytic leukemia

A 50-year-old male with chronic lymphocytic leukemia (CLL) was treated with fludarabine, cyclophosphamide and rituximab, which produced a complete remission. Eight months after the last dose of rituximab he had visual disturbance, diminished muscular strength in the right arm and vesicular-papular lesions in the left ophthalmic branch region of the V cranial nerve. These were initially interpreted as herpes virus encephalopathy (HVE), but brain magnetic resonance imaging (MRI) showed evidence of demyelination consistent with progressive multifocal leukoencephalopathy (PML). Cerebrospinal fluid (CSF) analysis was negative for varicella zoster virus (VZV) and John Cunningham virus (JCV) DNA. The clinical suggestion of PML prompted us to perform a brain biopsy and to start treatment with mefloquine. In the brain biopsy, histopathological features of demyelination were described and the polymerase chain reaction (PCR) identified JCV, confirming the diagnosis of PML. Treatment with mefloquine (250 mg/week) and dexamethasone (4 mg/day) was started and maintained for 6 months. A year later there was an almost complete resolution of the MRI lesions and the patient achieved a stable clinical state with persisting motor impairment and severe epilepsy. The patient is alive 38 months after diagnosis of PML, which is the longest known survival to date