Toward reducing the immunogenic potential of wheat flour: identification and characterization of wheat lines missing omega-5 gliadins encoded by the 1D chromosome.

KEY MESSAGE: Eleven wheat lines that are missing genes for the 1D-encoded omega-5 gliadins will facilitate breeding efforts to reduce the immunogenic potential of wheat flour for patients susceptible to wheat allergy. Efforts to reduce the levels of allergens in wheat flour that cause wheat-dependent exercise-induced anaphylaxis are complicated by the presence of genes encoding omega-5 gliadins on both chromosomes 1B and 1D of hexaploid wheat. In this study, we screened 665 wheat germplasm samples using gene specific DNA markers for omega-5 gliadins encoded by the genes on 1D chromosome that were obtained from the reference wheat Chinese Spring. Eleven wheat lines missing the PCR product corresponding to 1D omega-5 gliadin gene sequences were identified. Two of the lines contained the 1BL·1RS translocation. Relative quantification of gene copy numbers by qPCR revealed that copy numbers of 1D omega-5 gliadins in the other nine lines were comparable to those in 1D null lines of Chinese Spring, while copy numbers of 1B omega-5 gliadins were like those of Chinese Spring. 2-D immunoblot analysis of total flour proteins from the selected lines using a specific monoclonal antibody against the N-terminal sequence of omega-5 gliadin showed no reactivity in regions of the blots containing previously identified 1D omega-5 gliadins. Interestingly, RP-UPLC analysis of the gliadin fractions of the selected lines indicated that the expression of omega-1,2 gliadins was also significantly reduced in seven of the lines, implying that 1D omega-5 gliadin and 1D omega-1,2 gliadin genes are tightly linked on the Gli-D1 loci of chromosome 1D. Wheat lines missing the omega-5 gliadins encoded by the genes on 1D chromosome should be useful in future breeding efforts to reduce the immunogenic potential of wheat flour.

MYB3 plays an important role in lignin and anthocyanin biosynthesis under salt stress condition in Arabidopsis.

KEY MESSAGE: Nuclear-localized Arabidopsis MYB3 functions as a transcriptional repressor for regulation of lignin and anthocyanin biosynthesis under high salt conditions. Salinity stress is a major factor which reduces plant growth and crop yield worldwide. To improve growth of crops in high salinity environments, plant responses to salinity stress must be tightly controlled. Here, to further understand the regulation of plant responses under high salinity conditions, the function of the MYB3 transcription factor was studied as a repressor to control accumulation of lignin and anthocyanin under salt stress conditions. Nuclear-localized MYB3 forms a homodimer. It is ubiquitously expressed, especially in vascular tissues, with expression highly induced by NaCl in tissues such as roots, leaves, stems, and flowers. myb3 mutant plants exhibited longer root growth in high NaCl conditions than wild-type plants. However, several NaCl responsive genes were not significantly altered in myb3 compared to wild-type. Interestingly, high accumulation of lignin and anthocyanin occurred in myb3 under NaCl treatment, as well as increased expression of genes involved in lignin and anthocyanin biosynthesis, such as phenylalanine ammonia lyase 1 (PAL1), cinnamate 4-hydroxylase (C4H), catechol-O-methyltransferase (COMT), 4-coumaric acid-CoA ligase (4CL3), dihydroflavonol reductase (DFR), and leucoanthocyanidin dioxygenase (LDOX). According to yeast two-hybrid screenings, various transcription factors, including anthocyanin regulators Transparent Testa 8 (TT8) and Enhancer of Glabra 3 (EGL3), were isolated as MYB3 interacting proteins. MYB3 was characterized as a transcriptional repressor, with its repressor domain located in the C-terminus. Overall, these results suggest that nuclear-localized MYB3 functions as a transcriptional repressor to control lignin and anthocyanin accumulation under salinity stress conditions.

Adipose-derived stem cells decolonize skin Staphylococcus aureus by enhancing phagocytic activity of peripheral blood mononuclear cells in the atopic rats.

Staphylococcus aureus (S. aureus) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S. aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ+/IL-4+ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V+/7-AAD+ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163+ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and ß-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.

Deep-learned short tau inversion recovery imaging using multi-contrast MR images.

PURPOSE: To generate short tau, or short inversion time (TI), inversion recovery (STIR) images from three multi-contrast MR images, without additional scanning, using a deep neural network. METHODS: For simulation studies, we used multi-contrast simulation images. For in-vivo studies, we acquired knee MR images including 288 slices of T1 -weighted (T1 -w), T2 -weighted (T2 -w), gradient-recalled echo (GRE), and STIR images taken from 12 healthy volunteers. Our MR image synthesis method generates a new contrast MR image from multi-contrast MR images. We used a deep neural network to identify the complex relationships between MR images that show various contrasts for the same tissues. Our contrast-conversion deep neural network (CC-DNN) is an end-to-end architecture that trains the model to create one image from three (T1 -w, T2 -w, and GRE images). We propose a new loss function to take into account intensity differences, misregistration, and local intensity variations. The CC-DNN-generated STIR images were evaluated with four quantitative evaluation metrics, including mean squared error, peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and multi-scale SSIM (MS-SSIM). Furthermore, a subjective evaluation was performed by musculoskeletal radiologists. RESULTS: Our method showed improved results in all quantitative evaluations compared with other methods and received the highest scores in subjective evaluations by musculoskeletal radiologists. CONCLUSION: This study suggests the feasibility of our method for generating STIR sequence images without additional scanning that offered a potential alternative to the STIR pulse sequence when additional scanning is limited or STIR artifacts are severe.

Capsaicin induces atopic dermatitis-like manifestations through dysregulation of proteolytic system and alteration of filaggrin processing in rats.

Atopic dermatitis (AD) is a complex disease featuring pruritic skin inflammation. Many animal models have been developed. In a rat model, subcutaneous capsaicin injection within 48 hours after birth induces AD-like skin manifestations of dermatitis and scratching behaviour 3 weeks after the injection. When 2- to 4-week-old rats were injected with capsaicin, the lag period was shortened, and the severity of skin manifestations was significantly reduced, suggesting influences of postnatal development. Lgr6 is an epidermal stem cell marker that is normally restricted to the isthmus area of hair follicles at postnatal 2 weeks. Lgr6 persisted in the interfollicular epidermis of capsaicin-injected rats beyond 3 weeks after birth, indicating that capsaicin-induced skin manifestations were influenced by postnatal epidermal development. Capsaicin injection induced alteration of proteolytic processing of filaggrin and corneodesmosin, suggesting epidermal barrier dysfunction. Inappropriate degradation of matriptase was observed. Degrees of proteolysis of these proteins were corelated with the severity of manifestations, suggesting that inappropriate proteolysis might be a possible cause of the skin manifestations. These results strongly suggest that capsaicin may dysregulate the protease system, resulting in alteration of profilaggrin and corneodesmosin proteolysis and skin manifestations. These events may be influenced by postnatal epidermal development.

Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk.

PURPOSE: The human CAV1-CAV2 locus has been associated with susceptibility to primary open-angle glaucoma in four studies of Caucasian, Chinese, and Pakistani populations, although not in several other studies of non-Korean populations. In this study with Korean participants, the CAV1-CAV2 locus was investigated for associations with susceptibility to primary open-angle glaucoma accompanied by elevated intraocular pressure (IOP), namely, high-tension glaucoma (HTG), as well as with IOP elevation, which is a strong risk factor for glaucoma. METHODS: Two single nucleotide polymorphisms (SNPs) were genotyped in 1,161 Korean participants including 229 patients with HTG and 932 healthy controls and statistically examined for association with HTG susceptibility and IOP. One SNP was rs4236601 G>A, which had been reported in the original study, and the other SNP was rs17588172 T>G, which was perfectly correlated (r2=1) with another reported SNP rs1052990. Expression quantitative trait loci (eQTL) analysis was performed using GENe Expression VARiation (Genevar) data. RESULTS: Both SNPs were associated with HTG susceptibility, but the rs4236601 association disappeared when adjusted for the rs17588172 genotype and not vice versa. The minor allele G of rs17588172 was associated significantly with 1.5-fold increased susceptibility to HTG (p=0.0069) and marginally with IOP elevation (p=0.043) versus the major allele T. This minor allele was also associated with decreased CAV1 and CAV2 mRNA in skin and adipose according to the Genevar eQTL analysis. CONCLUSIONS: The minor allele G of rs17588172 in the CAV1-CAV2 locus is associated with decreased expression of CAV1 and CAV2 in some tissues, marginally with IOP elevation, and consequently with increased susceptibility to HTG.

Highly potent and selective pyrazolylpyrimidines as Syk kinase inhibitors.

A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectivity. Lead optimization efforts provided compounds with potent Syk inhibition in both enzymatic and TNF-α release assay.

Involvement of caspase-2 activation in aurora kinase inhibitor-induced cell death in axin-expressing L929 cells.

Axin is a multifunctional protein that participates in many cellular events including Wnt signaling and cell fate determination. Aurora kinase inhibitor (AKI)-induced cell death and cell membrane rupture is facilitated in L929 cells expressing axin (L-axin cells) through the activation of poly ADP-ribose polymerase (PARP). We observed that caspase-2 activity is required for AKI-induced cell death. Inhibition of caspase-2 activity suppressed AKI-induced PARP activation and mitochondrial dysfunction, resulting in a decrease in AKI-induced cell death. When an axin mutant deleted for the glycogen synthase kinase 3ß (GSK3ß)-binding domain was expressed in L929 cells (L-ΔGSK cells), AKI-induced caspase-2 activation and cell death decreased. AKI treatment reduced the expression of a 32-kDa caspase-2 splicing variant (caspase-2S) in most L-axin cells, but not in L-ΔGSK cells. These results suggest that AKI-induced caspase-2 activation in L-axin cells might be due to a decrease in the expression of caspase-2S, which inhibits caspase-2 activity. In addition, AKI treatment failed to activate caspase-8 and treatment with necrostatin inhibited AKI-induced cell death in L-axin cells, suggesting that the absence of caspase-8 activation might favor necrotic cell death. Axin expression may facilitate AKI-induced caspase-2 activation followed by activation of PARP and initiation of the necrotic cell death pathway.

An unusual case of persistent consolidation: Idiopathic lymphoid interstitial pneumonia.

Lymphocytic interstitial pneumonia (LIP) is a rare but largely benign interstitial lung disease, most frequently associated with HIV and autoimmune conditions. It is infrequently found to be an idiopathic condition. Diagnosis is complex and can require numerous invasive tests as evidenced in the case presented. The diagnosis is made from a combination of clinical, radiological, and histological features but the unusual radiological and clinical features meant diagnosis in our case required surgical biopsy. There is minimal evidence around best treatment although largely involves targeting the underlying cause. There is a small risk of transformation to lymphoma and fibrosis. Immunosuppression with steroids is the most common therapeutic strategy however in our case the radiographic changes spontaneously resolved. We present a case of an immunocompetent male presenting with significant radiological and histopathological findings of LIP, without significant symptomatology, that spontaneously resolved without intervention suggesting a monitoring approach may be a valid management strategy.

Development of SSR markers by next-generation sequencing of Korean landraces of chamoe (Cucumis melo var. makuwa).

The oriental melon (Cucumis melo var. makuwa), called 'chamoe' in Korean, is a popular fruit crop cultivated mainly in Asia and a high-market value crop in Korea. To provide molecular breeding resources for chamoe, we developed and characterized genomic SSR markers from the preliminary Illumina read assemblies of Gotgam chamoe (one of the major landraces; KM) and SW3 (the breeding parent). Mononucleotide motifs were the most abundant type of markers, followed by di-, tri-, tetra-, and pentanucleotide motifs. The most abundant dinucleotide was AT, followed by AG and AC, and AAT was the most abundant trinucleotide motif in both assemblies. Following our SSR-marker development strategy, we designed a total of 370 primer sets. Of these, 236 primer sets were tested, exhibiting 93 % polymorphism between KM and SW3. Those polymorphic SSRs were successfully amplified in the netted and Kirkagac melons, which respectively exhibited 81 and 76 % polymorphism relative to KM, and 32 and 38 % polymorphism relative to SW3. Seven selected SSR markers with a total of 17 alleles (2-3 alleles per locus) were used to distinguish between KM, SW3, and four chamoe cultivars. Our results represent the first attempt to provide genomic resources for Korean landraces for the purposes of chamoe breeding, as well as to discover a set of SSR markers capable of discriminating chamoe varieties from Korea and the rest of Asia, which possess little genetic diversity. This study establishes a highly efficient strategy for developing SSR markers from preliminary Illumina assemblies of AT-rich genomes.

Design Strategies for Anodes and Interfaces Toward Practical Solid-State Li-Metal Batteries.

Solid-state Li-metal batteries (based on solid-state electrolytes) offer excellent safety and exhibit high potential to overcome the energy-density limitations of current Li-ion batteries, making them suitable candidates for the rapidly developing fields of electric vehicles and energy-storage systems. However, establishing close solid-solid contact is challenging, and Li-dendrite formation in solid-state electrolytes at high current densities causes fatal technical problems (due to high interfacial resistance and short-circuit failure). The Li metal/solid electrolyte interfacial properties significantly influence the kinetics of Li-metal batteries and short-circuit formation. This review discusses various strategies for introducing anode interlayers, from the perspective of reducing the interfacial resistance and preventing short-circuit formation. In addition, 3D anode structural-design strategies are discussed to alleviate the stress caused by volume changes during charging and discharging. This review highlights the importance of comprehensive anode/electrolyte interface control and anode design strategies that reduce the interfacial resistance, hinder short-circuit formation, and facilitate stress relief for developing Li-metal batteries with commercial-level performance.

Surface engineering of inorganic solid-state electrolytes via interlayers strategy for developing long-cycling quasi-all-solid-state lithium batteries.

Lithium metal batteries (LMBs) with inorganic solid-state electrolytes are considered promising secondary battery systems because of their higher energy content than their Li-ion counterpart. However, the LMB performance remains unsatisfactory for commercialization, primarily owing to the inability of the inorganic solid-state electrolytes to hinder lithium dendrite propagation. Here, using an Ag-coated Li6.4La3Zr1.7Ta0.3O12 (LLZTO) inorganic solid electrolyte in combination with a silver-carbon interlayer, we demonstrate the production of stable interfacially engineered lab-scale LMBs. Via experimental measurements and computational modelling, we prove that the interlayers strategy effectively regulates lithium stripping/plating and prevents dendrite penetration in the solid-state electrolyte pellet. By coupling the surface-engineered LLZTO with a lithium metal negative electrode, a high-voltage positive electrode with an ionic liquid-based liquid electrolyte solution in pouch cell configuration, we report 800 cycles at 1.6 mA/cm2 and 25 °C without applying external pressure. This cell enables an initial discharge capacity of about 3 mAh/cm2 and a discharge capacity retention of about 85%.

A biomimetic compound eye lens for photocurrent enhancement at low temperatures.

In this study, an artificial compound eye lens (ACEL) was fabricated using a laser cutting machine and polyvinyl alcohol (PVA) solution. A laser cutter was used to punch micro-sized holes (500 µm diameter-the smallest possible diameter) into an acrylic plate; this punched plate was then placed on the aqueous PVA solution, and the water was evaporated. The plate was used as the mold to obtain a polydimethylsiloxane (PDMS) micro lens array film, which was fixed to a dome-shaped three-dimensional-printed mold for further PDMS curing, and a hemispherical compound eye lens was obtained. Using a gallium nitride (GaN) photodetector, a light detection experiment was performed with the ACEL, bare lens, and no lens by irradiating light at various angles under low temperatures. The photodetector with the ACEL generated a high photocurrent under several conditions. In particular, when the light was irradiated at 0° and below -20 °C, the photocurrent of the GaN sensor with the ACEL increased by 61% and 81% compared with the photocurrent of the GaN sensor with the bare lens and without a lens, respectively. In this study, a sensor for detecting light with ACEL was demonstrated in low-temperature environments, such as indoor refrigerated storages and external conditions in Antarctica and Arctic.

Design of a lithiophilic and electron-blocking interlayer for dendrite-free lithium-metal solid-state batteries.

All-solid-state batteries are a potential game changer in the energy storage market; however, their practical employment has been hampered by premature short circuits caused by the lithium dendritic growth through the solid electrolyte. Here, we demonstrate that a rational layer-by-layer strategy using a lithiophilic and electron-blocking multilayer can substantially enhance the performance/stability of the system by effectively blocking the electron leakage and maintaining low electronic conductivity even at high temperature (60°C) or under high electric field (3 V) while sustaining low interfacial resistance (13.4 ohm cm2). It subsequently results in a homogeneous lithium plating/stripping, thereby aiding in achieving one of the highest critical current densities (~3.1 mA cm-2) at 60°C in a symmetric cell. A full cell paired with a commercial-level cathode exhibits exceptionally long durability (>3000 cycles) and coulombic efficiency (99.96%) at a high current density (2 C; ~1.0 mA cm-2), which records the highest performance among all-solid-state lithium metal batteries reported to date.

Weight Change Alters the Small RNA Profile of Urinary Extracellular Vesicles in Obesity.

INTRODUCTION: Various kidney diseases reportedly show different urinary extracellular vesicle (EV) RNA profiles. Although obesity is one of the main causes of chronic kidney disease, the expression pattern of urinary EV RNA in obesity is uncertain. Our aim was to sequence the small RNA profiles of urinary EVs in obese patients before and after weight reduction and compare them to those of healthy volunteers (HVs). METHODS: We recruited age-sex-matched obese patients and HVs. The small RNA profiles of urinary EVs were analyzed using RNA sequencing. To evaluate the effect of weight reduction, small RNA profiles of urinary EVs 6 months after bariatric surgery were also analyzed. RESULTS: The proportion of urinary EVs transfer RNA and microRNA of obese patients differed from that of HVs. Obese patients showed differential expression of 1,343 small RNAs in urinary EVs compared to HVs (fold change ≥2 and p value <0.05). Among those, 61 small RNAs were upregulated in obese patients and downregulated after weight reduction, whereas 167 small RNAs were downregulated in obese patients and upregulated after weight reduction. RNA sequencing revealed the correlation between the specific urinary EV small RNAs and clinical parameters including body weight, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, serum glucose, estimated glomerular filtration rate, and albuminuria. CONCLUSION: Obese patients showed distinct urinary EV small RNA profiles compared to HVs. Weight reduction altered urinary EV small-RNA profiles in obese patients.

High-energy and durable lithium metal batteries using garnet-type solid electrolytes with tailored lithium-metal compatibility.

Lithium metal batteries using solid electrolytes are considered to be the next-generation lithium batteries due to their enhanced energy density and safety. However, interfacial instabilities between Li-metal and solid electrolytes limit their implementation in practical batteries. Herein, Li-metal batteries using tailored garnet-type Li7-xLa3-aZr2-bO12 (LLZO) solid electrolytes is reported, which shows remarkable stability and energy density, meeting the lifespan requirements of commercial applications. We demonstrate that the compatibility between LLZO and lithium metal is crucial for long-term stability, which is accomplished by bulk dopant regulating and dopant-specific interfacial treatment using protonation/etching. An all-solid-state with 5 mAh cm-2 cathode delivers a cumulative capacity of over 4000 mAh cm-2 at 3 mA cm-2, which to the best of our knowledge, is the highest cycling parameter reported for Li-metal batteries with LLZOs. These findings are expected to promote the development of solid-state Li-metal batteries by highlighting the efficacy of the coupled bulk and interface doping of solid electrolytes.

Analysis of an extended chromosome locus 2p14-21 for replication of the 2p16.3 association with glaucoma susceptibility.

PURPOSE: Susceptibility to primary open-angle glaucoma (POAG) has recently associated with three intergenic single-nucleotide polymorphisms (SNPs) on human chromosome 2p16.3, just outside of the POAG-linkage locus GLC1H (2p15-16.2), in an Afro-Caribbean population. Especially, association of one SNP (rs12994401) was very strong (odds ratio 35) and later replicated in Afro-Americans but not in Ghanaians or Japanese. An extended region was examined in this study to look for SNPs of cross-population association. METHODS: The three reported SNPs and all 63 SNPs considerably correlating with rs12994401 (r(2)≥0.3) in the African-descendent Yoruba were examined for POAG susceptibility association in a Korean population of 1,159 unrelated participants including 226 cases with glaucoma. As these 66 SNPs were spread from 2p14 to 2p21, all SNPs in this extended region were imputed for susceptibility association tests. RESULTS: No susceptibility association was detected with rs12994401 in comparisons between 933 controls and 188 POAG (or 175 high-tension glaucoma) cases (statistical power of 100%), as well as with all 19 other typed SNPs, using logistic regression with adjustment for age and gender. The other 46 SNPs were deemed non-polymorphic in Koreans. Among 21,201 SNPs located in 2p14-21, only 4,260 were imputed to be non-monomorphic, but none of them passed a significance level of multiple testing. No association was observed when the samples were stratified by age or gender. CONCLUSIONS: No typed or imputed SNPs within 2p14-21 showed association with susceptibility to POAG, suggesting that the population inconsistency in 2p16.3 association was unlikely due to linkage disequilibrium differences.

Salt tolerance of Arabidopsis thaliana requires maturation of N-glycosylated proteins in the Golgi apparatus.

Protein N-glycosylation in the endoplasmic reticulum (ER) and in the Golgi apparatus is an essential process in eukaryotic cells. Although the N-glycosylation pathway in the ER has been shown to regulate protein quality control, salt tolerance, and cellulose biosynthesis in plants, no biological roles have been linked functionally to N-glycan modifications that occur in the Golgi apparatus. Herein, we provide evidence that mutants defective in N-glycan maturation, such as complex glycan 1 (cgl1), are more salt-sensitive than wild type. Salt stress caused growth inhibition, aberrant root-tip morphology, and callose accumulation in cgl1, which were also observed in an ER oligosaccharyltransferase mutant, staurosporin and temperature sensitive 3a (stt3a). Unlike stt3a, cgl1 did not cause constitutive activation of the unfolded protein response. Instead, aberrant modification of the plasma membrane glycoprotein KORRIGAN 1/RADIALLY SWOLLEN 2 (KOR1/RSW2) that is necessary for cellulose biosynthesis occurred in cgl1 and stt3a. Genetic analyses identified specific interactions among rsw2, stt3a, and cgl1 mutations, indicating that the function of KOR1/RSW2 protein depends on complex N-glycans. Furthermore, cellulose deficient rsw1-1 and rsw2-1 plants were also salt-sensitive. These results establish that plant protein N-glycosylation functions beyond protein folding in the ER and is necessary for sufficient cell-wall formation under salt stress.

Deep-learned spike representations and sorting via an ensemble of auto-encoders.

Spike sorting refers to the technique of detecting signals generated by single neurons from multi-neuron recordings and is a valuable tool for analyzing the relationships between individual neuronal activity patterns and specific behaviors. Since the precision of spike sorting affects all subsequent analyses, sorting accuracy is critical. Many semi-automatic to fully-automatic spike sorting algorithms have been developed. However, due to unsatisfactory classification accuracy, manual sorting is preferred by investigators despite the intensive time and labor costs. Thus, there still is a strong need for fully automatic spike sorting methods with high accuracy. Various machine learning algorithms have been developed for feature extraction but have yet to show sufficient accuracy for spike sorting. Here we describe a deep learning-based method for extracting features from spike signals using an ensemble of auto-encoders, each with a distinct architecture for distinguishing signals at different levels of resolution. By utilizing ensemble of auto-encoder ensemble, where shallow networks better represent overall signal structure and deep networks better represent signal details, extraction of high-dimensional representative features for improved spike sorting performance is achieved. The model was evaluated on publicly available simulated datasets and single-channel and 4-channel tetrode in vivo datasets. Our model not only classified single-channel spikes with varying degrees of feature similarities and signal to noise levels with higher accuracy, but also more precisely determined the number of source neurons compared to other machine learning methods. The model also demonstrated greater overall accuracy for spike sorting 4-channel tetrode recordings compared to single-channel recordings.

Fat-saturated image generation from multi-contrast MRIs using generative adversarial networks with Bloch equation-based autoencoder regularization.

Obtaining multiple series of magnetic resonance (MR) images with different contrasts is useful for accurate diagnosis of human spinal conditions. However, this can be time consuming and a burden on both the patient and the hospital. We propose a Bloch equation-based autoencoder regularization generative adversarial network (BlochGAN) to generate a fat saturation T2-weighted (T2 FS) image from T1-weighted (T1-w) and T2-weighted (T2-w) images of human spine. To achieve this, our approach was to utilize the relationship between the contrasts using Bloch equation since it is a fundamental principle of MR physics and serves as a physical basis of each contrasts. BlochGAN properly generated the target-contrast images using the autoencoder regularization based on the Bloch equation to identify the physical basis of the contrasts. BlochGAN consists of four sub-networks: an encoder, a decoder, a generator, and a discriminator. The encoder extracts features from the multi-contrast input images, and the generator creates target T2 FS images using the features extracted from the encoder. The discriminator assists network learning by providing adversarial loss, and the decoder reconstructs the input multi-contrast images and regularizes the learning process by providing reconstruction loss. The discriminator and the decoder are only used in the training process. Our results demonstrate that BlochGAN achieved quantitatively and qualitatively superior performance compared to conventional medical image synthesis methods in generating spine T2 FS images from T1-w, and T2-w images.