Audio-video Synchronization with Arbitrary, Non-periodic Video Sources

The latency between audio and video streams of a device is usually measured using stock test videos. Although the use of stock test videos eases analysis, the test video differs materially from real-world videos, which tend to be far more diverse in content and encoding schemes, resulting in laborious experimental setup and inaccurate synchronization. This disclosure describes techniques to measure the latency between the audio and video streams of a given device using arbitrary, real-world, audio-visual footage (test video). Characteristic video and audio frames and their differences in timestamps (characteristic durations) are identified within the test video. The test video is played by the device-under-test while being recorded by a high-precision video camera. Characteristic durations of the recorded footage are determined. The differences in characteristic durations between the test and the recorded videos are statistically analyzed to determine the AV asynchrony of the device-under-test

Precise Latency Calculation for Audio-Video Synchronization

Synchronization between the audio and video tracks in recording equipment is usually achieved using an audio-first approach. In this approach, the timestamp of a target video frame is compared to the timestamp of the sound emitted during that frame, timestamps being counted in units of video frames. Videos have a relatively low sampling rate, e.g., a 60 frame-per-sec video has frames separated by 16.67 milliseconds. Thus, the measurement of audio-video asynchrony is imprecise. This disclosure describes video-first techniques for audio-video synchronization. A target video frame is captured, and its timestamp is mapped to the audio track. The audio track has millisecond-level time resolution due to high audio-sampling rates. Using the audio track, the timestamp of the sound (pulse) emitted during the target video frame is determined to millisecond accuracy. Timestamps of the target video frame and of the audio pulse are differenced to obtain a high-precision estimate of audio-video asynchrony

Development of scalable semi-continuous downstream processes

The goal of this work is to establish an intensified downstream scheme for stable, high-titer monoclonal antibody (mAb) processes to achieve increased manufacturing productivity with short cadence, reduced cost, and small facility footprint. Several continuous manufacturing technologies including multi-column chromatography for capture, automated low-pH viral inactivation (low-pH VI), and integrated pool-less polishing steps were evaluated following consistent development methodologies for several mAbs. This presentation aims to provide an overview of the approaches to developing and integrating these discrete technologies in one cohesive process flow that fits manufacturing requirements in a flexible manner. Development efforts are illustrated in three major areas. First, twin-column continuous capture chromatography (CaptureSMB) was evaluated systematically for equivalency assessment comparing to traditional batch operation for different molecules. Development data showed overall comparable chromatography performance, while certain trends were found to be molecule/process specific. For executing viral clearance studies, scalable models were developed using CaptureSMB and a surrogate system employing standard batch chromatography with flow path modifications to mimic the loading strategy of CaptureSMB. We also introduce a model-assisted process characterization approach toward validation of continuous twin-column capture chromatography owing to increased process understanding. Second, experimental studies and computational fluid dynamics (CFD) modeling were used to reduce the risk of product aggregation in low-pH VI manufacturing operation. For various mixing systems, localized low-pH zones were characterized quantitatively to avoid the undesirable conditions that could cause severe aggregate formation during acid adjustment. The modeling tool integrated with mAb aggregation measurements facilitates the optimization of operating parameters (e.g., titrant addition rate, impeller agitation) and automation strategy to ensure robust VI scale-up performance. Third, various scenarios of integrated pool-less polishing steps operated in flowthrough-flowthrough (FT-FT) or flowthrough-bind/elute (FT-B/E) mode were evaluated with or without inline adjustment between the two steps. Performance and quality attributes are compared for integrated and decoupled polishing steps, with an example describing the development and optimization workflow for a specific mAb process. Finally, implication to process development timelines, scale-up performance and practical challenges to process implementation in the new 2000-L manufacturing facility will be discussed

AS160 deficiency causes whole-body insulin resistance via composite effects in multiple tissues.

AS160 (Akt substrate of 160 kDa) is a Rab GTPase-activating protein implicated in insulin control of GLUT4 (glucose transporter 4) trafficking. In humans, a truncation mutation (R363X) in one allele of AS160 decreased the expression of the protein and caused severe postprandial hyperinsulinaemia during puberty. To complement the limited studies possible in humans, we generated an AS160-knockout mouse. In wild-type mice, AS160 expression is relatively high in adipose tissue and soleus muscle, low in EDL (extensor digitorum longus) muscle and detectable in liver only after enrichment. Despite having lower blood glucose levels under both fasted and random-fed conditions, the AS160-knockout mice exhibited insulin resistance in both muscle and liver in a euglycaemic clamp study. Consistent with this paradoxical phenotype, basal glucose uptake was higher in AS160-knockout primary adipocytes and normal in isolated soleus muscle, but their insulin-stimulated glucose uptake and overall GLUT4 levels were markedly decreased. In contrast, insulin-stimulated glucose uptake and GLUT4 levels were normal in EDL muscle. The liver also contributes to the AS160-knockout phenotype via hepatic insulin resistance, elevated hepatic expression of phosphoenolpyruvate carboxykinase isoforms and pyruvate intolerance, which are indicative of increased gluconeogenesis. Overall, as well as its catalytic function, AS160 influences expression of other proteins, and its loss deregulates basal and insulin-regulated glucose homoeostasis, not only in tissues that normally express AS160, but also by influencing liver function

High speed optical coherence microscopy with autofocus adjustment and a miniaturized endoscopic imaging probe

Optical coherence microscopy (OCM) is a promising technique for high resolution cellular imaging in human tissues. An OCM system for high-speed en face cellular resolution imaging was developed at 1060 nm wavelength at frame rates up to 5 Hz with resolutions of < 4 µm axial and < 2 µm transverse. The system utilized a novel polarization compensation method to combat wavelength dependent source polarization and achieve broadband electro-optic phase modulation compatible with ultrahigh axial resolution. In addition, the system incorporated an auto-focusing feature that enables precise, near real-time alignment of the confocal and coherence gates in tissue, allowing user-friendly optimization of image quality during the imaging procedure. Ex vivo cellular images of human esophagus, colon, and cervix as well as in vivo results from human skin are presented. Finally, the system design is demonstrated with a miniaturized piezoelectric fiber-scanning probe which can be adapted for laparoscopic and endoscopic imaging applications.National Institutes of Health (U.S.) (R01-CA75289-13)National Institutes of Health (U.S.) R01-EY11289-25United States. Air Force Office of Scientific Research (FA9550-07-1-0101)United States. Air Force Office of Scientific Research (FA9550-07-1-0014)Max Planck Society for the Advancement of ScienceNational Institutes of Health (U.S.) (Fellowship) (F31 EB005978

IL-10 deficiency accelerates type 1 diabetes development via modulation of innate and adaptive immune cells and gut microbiota in BDC2.5 NOD mice

Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of insulin-producing β cells. BDC2.5 T cells in BDC2.5 CD4+ T cell receptor transgenic Non-Obese Diabetic (NOD) mice (BDC2.5+ NOD mice) can abruptly invade the pancreatic islets resulting in severe insulitis that progresses rapidly but rarely leads to spontaneous diabetes. This prevention of diabetes is mediated by T regulatory (Treg) cells in these mice. In this study, we investigated the role of interleukin 10 (IL-10) in the inhibition of diabetes in BDC2.5+ NOD mice by generating Il-10-deficient BDC2.5+ NOD mice (BDC2.5+Il-10-/- NOD mice). Our results showed that BDC2.5+Il-10-/- NOD mice displayed robust and accelerated diabetes development. Il-10 deficiency in BDC2.5+ NOD mice promoted the generation of neutrophils in the bone marrow and increased the proportions of neutrophils in the periphery (blood, spleen, and islets), accompanied by altered intestinal immunity and gut microbiota composition. In vitro studies showed that the gut microbiota from BDC2.5+Il-10-/- NOD mice can expand neutrophil populations. Moreover, in vivo studies demonstrated that the depletion of endogenous gut microbiota by antibiotic treatment decreased the proportion of neutrophils. Although Il-10 deficiency in BDC2.5+ NOD mice had no obvious effects on the proportion and function of Treg cells, it affected the immune response and activation of CD4+ T cells. Moreover, the pathogenicity of CD4+ T cells was much increased, and this significantly accelerated the development of diabetes when these CD4+ T cells were transferred into immune-deficient NOD mice. Our study provides novel insights into the role of IL-10 in the modulation of neutrophils and CD4+ T cells in BDC2.5+ NOD mice, and suggests important crosstalk between gut microbiota and neutrophils in type 1 diabetes development

Reveal a hidden highly toxic substance in biochar to support its effective elimination strategy

With the aim to develop optimized biochar with minimal contaminants, it is important significance to broaden the understanding of biochar. Here, we disclose for the first time, a highly toxic substance (metal cyanide, MCN, such as KCN or NaCN) in biochar. The cyanide ion (CN−) content in biochar can be up to 85,870 mg/kg, which is determined by the inherent metal content and type in the biomass with K and Na increasing and Ca, Mg and Fe decreasing its formation. Density functional theory (DFT) analysis shows that unstable alkali oxygen-containing metal salts such as K2CO3 can induce an N rearrangement reaction to produce for example, KOCN. The strong reducing character of the carbon matrix further converts KOCN to KCN, thus resulting biochar with high risk. However, the stable Mg, Ca and Fe salts in biomass cannot induce an N rearrangement reaction due to their high binding energies. We therefore propose that high valent metal chloride salts such as FeCl3 and MgCl2 could be used to inhibit the production of cyanide via metal interactive reaction. These findings open a new point of view on the potential risk of biochar and provide a mitigation solution for biochar’s sustainable application

The Second Monocular Depth Estimation Challenge

This paper discusses the results for the second edition of the Monocular Depth Estimation Challenge (MDEC). This edition was open to methods using any form of supervision, including fully-supervised, self-supervised, multi-task or proxy depth. The challenge was based around the SYNS-Patches dataset, which features a wide diversity of environments with high-quality dense ground-truth. This includes complex natural environments, e.g. forests or fields, which are greatly underrepresented in current benchmarks. The challenge received eight unique submissions that outperformed the provided SotA baseline on any of the pointcloud- or image-based metrics. The top supervised submission improved relative F-Score by 27.62%, while the top self-supervised improved it by 16.61%. Supervised submissions generally leveraged large collections of datasets to improve data diversity. Self-supervised submissions instead updated the network architecture and pretrained backbones. These results represent a significant progress in the field, while highlighting avenues for future research, such as reducing interpolation artifacts at depth boundaries, improving self-supervised indoor performance and overall natural image accuracy.Comment: Published at CVPRW202

Impact of the Location of CpG Methylation within the GSTP1 Gene on Its Specificity as a DNA Marker for Hepatocellular Carcinoma

Hypermethylation of the glutathione S-transferase π 1 (GSTP1) gene promoter region has been reported to be a potential biomarker to distinguish hepatocellular carcinoma (HCC) from other liver diseases. However, reports regarding how specific a marker it is have ranged from 100% to 0%. We hypothesized that, to a large extent, the variation of specificity depends on the location of the CpG sites analyzed. To test this hypothesis, we compared the methylation status of the GSTP1 promoter region of the DNA isolated from HCC, cirrhosis, hepatitis, and normal liver tissues by bisulfite–PCR sequencing. We found that the 5′ region of the position −48 nt from the transcription start site of the GSTP1 gene is selectively methylated in HCC, whereas the 3′ region is methylated in all liver tissues examined, including normal liver and the HCC tissue. Interestingly, when DNA derived from fetal liver and 11 nonhepatic normal tissue was also examined by bisulfite-PCR sequencing, we found that methylation of the 3′ region of the promoter appeared to be liver-specific. A methylation-specific PCR assay targeting the 5′ region of the promoter was developed and used to quantify the methylated GSTP1 gene in various diseased liver tissues including HCC. When we used an assay targeting the 3′ region, we found that the methylation of the 5′-end of the GSTP1 promoter was significantly more specific than that of the 3′-end (97.1% vs. 60%, p<0.0001 by Fisher's exact test) for distinguishing HCC (n = 120) from hepatitis (n = 35) and cirrhosis (n = 35). Encouragingly, 33.8% of the AFP-negative HCC contained the methylated GSTP1 gene. This study clearly demonstrates the importance of the location of CpG site methylation for HCC specificity and how liver-specific DNA methylation should be considered when an epigenetic DNA marker is studied for detection of HCC