Understanding Neural Pathways in Zebrafish through Deep Learning and High Resolution Electron Microscope Data

The tracing of neural pathways through large volumes of image data is an incredibly tedious and time-consuming process that significantly encumbers progress in neuroscience. We are exploring deep learning's potential to automate segmentation of high-resolution scanning electron microscope (SEM) image data to remove that barrier. We have started with neural pathway tracing through 5.1GB of whole-brain serial-section slices from larval zebrafish collected by the Center for Brain Science at Harvard University. This kind of manual image segmentation requires years of careful work to properly trace the neural pathways in an organism as small as a zebrafish larva (approximately 5mm in total body length). In automating this process, we would vastly improve productivity, leading to faster data analysis and breakthroughs in understanding the complexity of the brain. We will build upon prior attempts to employ deep learning for automatic image segmentation extending methods for unconventional deep learning data.Comment: 8 pages, 5 figures (1a to 5c), PEARC '18: Practice and Experience in Advanced Research Computing, July 22--26, 2018, Pittsburgh, PA, US

CHANGING AN ONLINE VIDEO MEETING BACKGROUND IN REAL-TIME USING DEEP LEARNING

This proposal provides a technique to change an online video meeting background in real-time using deep learning. By changing the background video for participants of a meeting, the participants can protect their accuracy. The background-changing technique of this proposal may include a deep learning model for video semantic segmentation. One or more Spatio-Temporal Transformer Gated Recurrent Units (STGRUs) may be utilized to enhance classification accuracy and to add an optical flow into the model; thereby increasing calculation speed

Direct measurement of neutrons induced in lead by cosmic muons at a shallow underground site

Neutron production in lead by cosmic muons has been studied with a Gadolinium doped liquid scintillator detector. The detector was installed next to the Muon-Induced Neutron Indirect Detection EXperiment (MINIDEX), permanently located in the T\"ubingen shallow underground laboratory where the mean muon energy is approximately 7 GeV. The MINIDEX plastic scintillators were used to tag muons; the neutrons were detected through neutron capture and neutron-induced nuclear recoil signals in the liquid scintillator detector. Results on the rates of observed neutron captures and nuclear recoils are presented and compared to predictions from GEANT4-9.6 and GEANT4-10.3. The predicted rates are significantly too low for both versions of GEANT4. For neutron capture events, the observation exceeds the predictions by factors of $1.65\,\pm\,0.02\,\textrm{(stat.)}\,\pm\,0.07\,\textrm{(syst.)}$ and $2.58\,\pm\,0.03\,\textrm{(stat.)}\,\pm\,0.11\,\textrm{(syst.)}$ for GEANT4-9.6 and GEANT4-10.3, respectively. For neutron nuclear recoil events, which require neutron energies above approximately 5 MeV, the factors are even larger, $2.22\,\pm\,0.05\,\textrm{(stat.)}\,\pm\,0.25\,\textrm{(syst.)}$ and $3.76\,\pm\,0.09\,\textrm{(stat.)}\,\pm\,0.41\,\textrm{(syst.)}$, respectively. Also presented is the first statistically significant measurement of the spectrum of neutrons induced by cosmic muons in lead between 5 and 40 MeV. It was obtained by unfolding the nuclear recoil spectrum. The observed neutron spectrum is harder than predicted by GEANT4. An investigation of the distribution of the time difference between muon tags and nuclear recoil signals confirms the validity of the unfolding procedure and shows that GEANT4 cannot properly describe the time distribution of nuclear recoil events. In general, the description of the data is worse for GEANT4-10.3 than for GEANT4-9.6.Comment: 29 pages, 22 figures, 4 table

Genome sequence and genetic linkage analysis of Shiitake mushroom _Lentinula edodes_

_Lentinula edodes_ (Shiitake/Xianggu) is an important cultivated mushroom. Understanding the genomics and functional genomics of _L. edodes_ allows us to improve its cultivation and quality. Genome sequence is a key to develop molecular genetic markers for breeding and genetic manipulation. We sequenced the genome of _L. edodes_ monokaryon L54A using Roche 454 and ABI SOLiD genome sequencing. Sequencing reads of about 1400Mb were de novo assembled into a 40.2 Mb genome sequence. We compiled the genome sequence into a searchable database with which we have been annotating the genes and analyzing the metabolic pathways. In addition, we have been using many molecular techniques to analyze genes differentially expressed during development. Gene ortholog groups of _L. edodes_ genome sequence compared across genomes of several fungi including mushrooms identified gene families unique to mushroom-forming fungi. We used a mapping population of haploid basidiospores of dikaryon L54 for genetic linkage analysis. High-quality variations such as single nucleotide polymorphisms, insertions, and deletions of the mapping population formed a high-density genetic linkage map. We compared the linkage map to the _L. edodes_ L54A genome sequence and located selected quantitative trait loci. The Shiitake community will benefit from these resources for genetic studies and breeding.
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Bioluminescence Imaging of Heme Oxygenase-1 Upregulation in the Gua Sha Procedure

Gua Sha is a traditional Chinese folk therapy that employs skin scraping to cause subcutaneous microvascular blood extravasation and bruises. The protocol for bioluminescent optical imaging of HO-1-luciferase transgenic mice reported in this manuscript provides a rapid in vivo assay of the upregulation of the heme oxygenase-1 (HO-1) gene expression in response to the Gua Sha procedure. HO-1 has long been known to provide cytoprotection against oxidative stress. The upregulation of HO-1, assessed by the bioluminescence output, is thought to represent an antioxidative response to circulating hemoglobin products released by Gua Sha. Gua Sha was administered by repeated strokes of a smooth spoon edge over lubricated skin on the back or other targeted body part of the transgenic mouse until petechiae (splinter hemorrhages) or ecchymosis (bruises) indicative of extravasation of blood from subcutaneous capillaries was observed. After Gua Sha, bioluminescence imaging sessions were carried out daily for several days to follow the dynamics of HO-1 expression in multiple internal organs

Deficiency of FLCN in Mouse Kidney Led to Development of Polycystic Kidneys and Renal Neoplasia

The Birt–Hogg–Dubé (BHD) disease is a genetic cancer syndrome. The responsible gene, BHD, has been identified by positional cloning and thought to be a novel tumor suppressor gene. BHD mutations cause many types of diseases including renal cell carcinomas, fibrofolliculomas, spontaneous pneumothorax, lung cysts, and colonic polyps/cancers. By combining Gateway Technology with the Ksp-Cre gene knockout system, we have developed a kidney-specific BHD knockout mouse model. BHDflox/flox/Ksp-Cre mice developed enlarged kidneys characterized by polycystic kidneys, hyperplasia, and cystic renal cell carcinoma. The affected BHDflox/flox/Ksp-Cre mice died of renal failure at approximate three weeks of age, having blood urea nitrogen levels over tenfold higher than those of BHD flox/+/Ksp-Cre and wild-type littermate controls. We further demonstrated that these phenotypes were caused by inactivation of BHD and subsequent activation of the mTOR pathway. Application of rapamycin, which inhibits mTOR activity, to the affected mice led to extended survival and inhibited further progression of cystogenesis. These results provide a correlation of kidney-targeted gene inactivation with renal carcinoma, and they suggest that the BHD product FLCN, functioning as a cyst and tumor suppressor, like other hamartoma syndrome–related proteins such as PTEN, LKB1, and TSC1/2, is a component of the mTOR pathway, constituting a novel FLCN-mTOR signaling branch that regulates cell growth/proliferation

Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)

Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8; 21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, similar to 40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21)

Tailored design of graphitic biochar for high-efficiency and chemical-free microwave-assisted removal of refractory organic contaminants

Energy-saving, chemical-free, and high-efficiency microwave (MW)-assisted water treatment can be greatly facilitated via tailored design of an economical, sustainable, and ‘green’ carbonaceous catalyst. In this study, various biochars (BC) were pyrolyzed from two lignocellulosic waste biomasses, oak (O) and apple tree (A), at a high temperature (900 °C) and under different gases (N2 and CO2). The holistic characterization by advanced spectroscopic techniques demonstrated that CO2 pyrolysis of feedstock with more lignin (i.e., oak), produced biochar with increased aromaticity and degree of carbonization. CO2 modification created a hierarchical porous structure, improved surface hydrophilicity, polarity, and acidity, and provided higher densities of near-surface functionalities of the biochar. Without MW irradiation, ABC-900C (1 g L−1) provided the highest adsorption (52.6%, 1 min) of 2,4-dichlorophenoxy acetic acid (2,4-D) ascribed to large specific surface area, high micropore content, appropriate pore size, and abundant active groups. OBC-900C (1 g L−1) enabled significantly increased 2,4-D removal (81.6%, 1 min) under MW irradiation (90 °C) in contrast with an oil bath (55.7%, 90 °C, 1 min) and room temperature (33.9%, 1 min) conditions, due to its highest graphitization degree and medium-developed microporous structure. The MW-induced thermal effect formed “hot spots” on the biochar surface as evidenced by elevated temperature of the bulk solution and lowered energy consumption of the MW reactor in the presence of OBC-900C, compared to those of the other biochars. The scavenging tests suggested that the generation of highly oxidative hydroxyl (•OH), anionic superoxide (O2 •−), and singlet oxygen (1O2) radicals contributed to the removal of 2,4-D. This study has demonstrated that biochar with customized structure and high organic adsorption capacity can act as an effective MW absorber suitable for rapid and improved removal of toxic organics

National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio : a pooled analysis of 458 population-based studies in Asian and Western countries

Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and nonHDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since similar to 1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at similar to 0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as similar to 0.7 per decade in Swiss men (equivalent to similar to 26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.Peer reviewe

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe