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The clinical progression of neurodegenerative diseases correlates with the spread of proteinopathy in the brain. The current understanding of the mechanism of proteinopathy spread is far from complete. Here, we propose that inflammation is fundamental to proteinopathy spread. A sequence variant of α-synuclein (V40G) was much less capable of fibril formation than wild-type α-synuclein (WT-syn) and, when mixed with WT-syn, interfered with its fibrillation. However, when V40G was injected intracerebrally into mice, it induced aggregate spreading even more effectively than WT-syn. Aggregate spreading was preceded by sustained microgliosis and inflammatory responses, which were more robust with V40G than with WT-syn. Oral administration of an anti-inflammatory agent suppressed aggregate spreading, inflammation, and behavioral deficits in mice. Furthermore, exposure of cells to inflammatory cytokines increased the cell-to-cell propagation of α-synuclein. These results suggest that the inflammatory microenvironment is the major driver of the spread of synucleinopathy in the brain.

Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology. We describe spatial molecular imaging, a system that measures RNAs and proteins in intact biological samples at subcellular resolution by performing multiple cycles of nucleic acid hybridization of fluorescent molecular barcodes. We demonstrate that spatial molecular imaging has high sensitivity (one or two copies per cell) and very low error rate (0.0092 false calls per cell) and background (~0.04 counts per cell). The imaging system generates three-dimensional, super-resolution localization of analytes at ~2 million cells per sample. Cell segmentation is morphology based using antibodies, compatible with formalin-fixed, paraffin-embedded samples. We measured multiomic data (980 RNAs and 108 proteins) at subcellular resolution in formalin-fixed, paraffin-embedded tissues (nonsmall cell lung and breast cancer) and identified18 distinct cell types, ten unique tumor microenvironments and 100 pairwise ligand-receptor interactions. Data on800,000 single cells and ~260 million transcripts can be accessed at http://nanostring.com/CosMx-dataset .

Cell-to-cell propagation of α-synuclein is thought to be the underlying mechanism of Parkinson’s disease progression. Recent evidence suggests that inflammation plays an important role in the propagation of protein aggregates. However, the mechanism by which inflammation regulates the propagation of aggregates remains unknown. Here, using in vitro cultures, we found that soluble factors secreted from activated microglia promote cell-to-cell propagation of α-synuclein and further showed that among these soluble factors, TNF-α had the most robust stimulatory activity. Treatment of neurons with TNF-α triggered cellular senescence, as shown by transcriptomic analyses demonstrating induction of senescence-associated genes and immunoanalysis of senescence phenotype marker proteins. Interestingly, secretion of α-synuclein was increased in senescent neurons, reflecting acquisition of a senescence-associated secretory phenotype (SASP). Using vacuolin-1, an inhibitor of lysosomal exocytosis, and RNAi against rab27a, we demonstrated that the SASP was mediated by lysosomal exocytosis. Correlative light and electron microscopy and immunoelectron microscopy confirmed that propagating α-synuclein aggregates were present in electron-dense lysosome-like compartments. TNF-α promoted the SASP through stimulation of lysosomal exocytosis, thereby increasing the secretion of α-synuclein. Collectively, these results suggest that TNF-α is the major inflammatory factor that drives cell-to-cell propagation of α-synuclein by promoting the SASP and subsequent secretion of α-synuclein.

To develop and test the performance of deep convolutional neural networks (DCNNs) for automated classification of age and sex on chest radiographs (CXR). We obtained 112,120 frontal CXRs from the NIH ChestX-ray14 database performed in 48,780 females (44%) and 63,340 males (56%) ranging from 1 to 95 years old. The dataset was split into training (70%), validation (10%), and test (20%) datasets, and used to fine-tune ResNet-18 DCNNs pretrained on ImageNet for (1) determination of sex (using entire dataset and only pediatric CXRs); (2) determination of age

Direct reprogramming/direct conversion/transdifferentiation is a process that induces conversion between completely different matured (differentiated) cells in higher organisms. Unlike the process of reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) and re-differentiation into the desired cell types, differentiated cells undergo the conversion into another type of differentiated cells without going through the iPSCs state. Osteoarthritis (OA) is the most common type of arthritis that causes a significant deterioration in patients’ quality of life. The high prevalence of OA as well as the current lack of disease-modifying drugs has led to a rise in regenerative strategy for OA treatment. Regenerative therapy in OA started with the concept of engraftment of the administered cells within the cartilage lesion and differentiation to chondrocytes after the engraftment. However, recent studies show that cells, particularly when injected in suspension, rapidly undergo apoptosis after exerting a transient paracrine effect. In this perspective review, the general overview and current status of direct conversion are introduced along with the conceptual strategy and future directions for possible application of regenerative therapy using stem cells in OA. In vivo direct conversion may open a new stage of regenerative medicine for OA treatment. Recent advances in in vivo gene transfer and smart biomaterials can bring the concept into reality in near future. Direct conversion can be a new type of treatment technology that has the potential to overcome the limitations of current cell therapy.

This study explored the impact of reduced-fat meat emulsion with pre-emulsified duck skin and hydrocolloids on physicochemical properties such as cooking loss, emulsion stability, apparent viscosity, protein solubility, and texture profile analysis. Six different reduced-fat meat emulsions were produced: control (pork back fat), T1 (duck skin, DS), T2 (pre-emulsified with duck skin, PDS), T3 (PDS + 2% carrageenan), T4 (PDS + 2% alginate), T5 (PDS + 2% pectin), and T6 (PDS + 2% guar gum). Moisture content, protein content, yellowness, and apparent viscosity of reduced-fat emulsion with PDS and hydrocolloids were all higher (P

We have previously demonstrated functional and molecular changes in hippocampal subfields in individuals with schizophrenia (SZ) psychosis associated with hippocampal excitability. In this study, we use RNA-seq and assess global transcriptome changes in the hippocampal subfields, DG, CA3, and CA1 from individuals with SZ psychosis and controls to elucidate subfield-relevant molecular changes. We also examine changes in gene expression due to antipsychotic medication in the hippocampal subfields from our SZ ON- and OFF-antipsychotic medication cohort. We identify unique subfield-specific molecular profiles in schizophrenia postmortem samples compared with controls, implicating astrocytes in DG, immune mechanisms in CA3, and synaptic scaling in CA1. We show a unique pattern of subfield-specific effects by antipsychotic medication on gene expression levels with scant overlap of genes differentially expressed by SZ disease effect versus medication effect. These hippocampal subfield changes serve to confirm and extend our previous model of SZ and can explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With future characterization using single-cell studies, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify further potential hippocampal-based therapeutic targets.

The origin of efficiency-lifetime trade-off in triplet–triplet fusion (TTF) type blue fluorescent organic light-emitting diodes (OLEDs) was investigated and the device structure to resolve the issue was developed. The efficiency and lifetime were simultaneously improved in the blue OLEDs by developing a multilayer hole transport stack which can adjust carrier densities and recombination zone in the emitting layer (EML). It was found that electron leakage from EML and high spatial density of excitons in the vicinity of the electron blocking layer for high TTF rates by narrow recombination zone are the detrimental factors for efficiency-lifetime trade-off. A multilayer hole transport stack employing a deep highest occupied molecular orbital hole transport layer and an electron blocking layer combined with an appropriate hole blocking layer simultaneously improved the power efficiency by 16% at 500 cd/m2 and lifetime by almost 100% (from 73 h up to 145 h). In addition, the low efficiency in the low luminance region was also completely controlled, resulting in negligible efficiency variation in the entire luminance range.

Although polycarbonate (PC) materials are well known to have poor adhesion to other surfaces, few studies have been conducted on the improvement of their adhesive properties via surface chemical functionalization. Herein, we report the enhancement in the adhesion properties of PC by adapting two silane coupling agents, namely (3-glycidoxypropyl) methyldiethoxysilane (GPTMS) and (3-aminopropyl) trimethoxysilane (APTMS), on the surface. We tested the adhesion with an epoxy-based adhesive consisting of bisphenol A diglycidyl ether (BADGE) and trientine (trien). The chemical interaction between the amine groups of the hardener (trien) and the epoxy rings of an epoxy-functionalized PC (PC-GPTMS) sample surface was observed with X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. We found that the amine-functionalized PC (PC-APTMS) can also form crosslinked polymeric structures with the BADGE after curing. Compared to the bare PC, an increase in the shear strength of up to 168% and 163% was observed from the PC-GPTMS and PC-APTMS, respectively. In contrast, the ultraviolet-ozone (UVO) and O2 plasma-treated samples showed a negligible increase in adhesion strength. These results strongly suggest that the chemical functionalization of PC substrates with coupling agents significantly enhances the adhesion properties of PCs.

An automated method for identifying the anatomical region of an image independent of metadata labels could improve radiologist workflow (e.g., automated hanging protocols) and help facilitate the automated curation of large medical imaging data sets for machine learning purposes. Deep learning is a potential tool for this purpose. To develop and test the performance of deep convolutional neural networks (DCNN) for the automated classification of pediatric musculoskeletal radiographs by anatomical area. We utilized a database of 250 pediatric bone radiographs (50 each of the shoulder, elbow, hand, pelvis and knee) to train 5 DCNNs, one to detect each anatomical region amongst the others, based on ResNet-18 pretrained on ImageNet (transfer learning). For each DCNN, the radiographs were randomly split into training (64%), validation (12%) and test (24%) data sets. The training and validation data sets were augmented 30 times using standard preprocessing methods. We also tested our DCNNs on a separate test set of 100 radiographs from a single institution. Receiver operating characteristics (ROC) with area under the curve (AUC) were used to evaluate DCNN performances. All five DCNN trained for classification of the radiographs into anatomical region achieved ROC AUC of 1, respectively, for both test sets. Classification of the test radiographs occurred at a rate of 33 radiographs per s. DCNNs trained on a small set of images with 30 times augmentation through standard processing techniques are able to automatically classify pediatric musculoskeletal radiographs into anatomical region with near-perfect to perfect accuracy at superhuman speeds. This concept may apply to other body parts and radiographic views with the potential to create an all-encompassing semantic-labeling DCNN.

Ensuring correct radiograph view labeling is important for machine learning algorithm development and quality control of studies obtained from multiple facilities. The purpose of this study was to develop and test the performance of a deep convolutional neural network (DCNN) for the automated classification of frontal chest radiographs (CXRs) into anteroposterior (AP) or posteroanterior (PA) views. We obtained 112,120 CXRs from the NIH ChestX-ray14 database, a publicly available CXR database performed in adult (106,179 (95%)) and pediatric (5941 (5%)) patients consisting of 44,810 (40%) AP and 67,310 (60%) PA views. CXRs were used to train, validate, and test the ResNet-18 DCNN for classification of radiographs into anteroposterior and posteroanterior views. A second DCNN was developed in the same manner using only the pediatric CXRs (2885 (49%) AP and 3056 (51%) PA). Receiver operating characteristic (ROC) curves with area under the curve (AUC) and standard diagnostic measures were used to evaluate the DCNN’s performance on the test dataset. The DCNNs trained on the entire CXR dataset and pediatric CXR dataset had AUCs of 1.0 and 0.997, respectively, and accuracy of 99.6% and 98%, respectively, for distinguishing between AP and PA CXR. Sensitivity and specificity were 99.6% and 99.5%, respectively, for the DCNN trained on the entire dataset and 98% for both sensitivity and specificity for the DCNN trained on the pediatric dataset. The observed difference in performance between the two algorithms was not statistically significant (p = 0.17). Our DCNNs have high accuracy for classifying AP/PA orientation of frontal CXRs, with only slight reduction in performance when the training dataset was reduced by 95%. Rapid classification of CXRs by the DCNN can facilitate annotation of large image datasets for machine learning and quality assurance purposes.

A series of M-quinolate complexes were theoretically investigated to understand the effect of metal ions on electronic and charge transport properties by employing density functional theory simulation. It was found that both electronic and carrier transport properties in M-quinolate materials significantly depend on singly oxidized metal ions. In particular, Csq apparently showed an excellent advantage over other M-quinolate materials (M = Li, Na, K, Rb, Cs, Cu, Ag, and Au) in terms of electron mobility and injection. In addition, the dimerization and vertical detachment energies of all M-quinolate materials were compared to understand self-aggregation effect on carrier transport. As a result, it is expected that Csq is not only likely to be present in dimer form, but also reduce the density of electron traps in electron transporting materials.

The effect of fermented red beet (FRB) on shelf-life of low-salt frankfurters stored for 4 weeks was investigated. The pH, volatile basic nitrogen (VBN), lightness, and yellowness of frankfurters decreased with increasing levels of FRB, whereas the redness of frankfurters increased with increasing levels of FRB. The VBN, thiobarbituric acid reactive substance values, total viable count, and redness of all treatments decreased with increasing period of refrigeration storage. The appearance, color, and juiciness scores of the control and treatments decreased with increasing period of refrigeration storage. However, there was no significant (p > 0.05) difference among the treatments except for the color of T3 (3.0% FRB) and juiciness of T4 (5.0% FRB). The flavor, tenderness, and overall acceptability scores of all the treatments decreased with increasing storage periods. These results demonstrated that FRB can be added to low-salt frankfurters to maintain their qualities and extend the shelf-life of refrigerated storage.

The objective of this study was to investigate the physicochemical and textural properties of heat-induced gels prepared with pork muscles irradiated with gamma rays, electron beams, and X-rays. Pork muscles were irradiated at 5 kGy using the different irradiation sources, and heat-induced gels were prepared from the irradiated pork muscles at a protein concentration of 5 mg/mL. Each irradiation treatment produced lower water-holding capacity, protein solubility, apparent viscosity, hardness, springiness, cohesiveness, gumminess, and chewiness than the control gel prepared with non-irradiated pork muscle (P

Autism spectrum disorders (ASDs) are a heterogeneous group of psychiatric illness characterized by common core symptoms including sociability deficits and stereotyped behaviors. ASD is caused by various genetic and non-genetic factors. The genetic effects of autism-related genes are usually global and are presented with multiple symptoms, which hamper understanding of the mechanism through which the diverse causes of ASD produce common symptoms. In the present study, we demonstrate that genetic or molecular disruption of an array of molecular networks centered on adenylyl cyclase type-5 (AC5 or ADCY5) in the dorsal striatum produces autistic-like behaviors. AC5 knockout (KO) mice exhibit increased repetitive behaviors and sociability deficits, the two core domains of ASD, and that siRNA-mediated suppression of AC5 within the dorsal striatum is sufficient to replicate these behavioral phenotypes. Notably, the autistic-like behaviors of AC5 KO mice are rescued by blocking mGluR5 glutamate receptors within the dorsal striatum. Furthermore, pharmacological or siRNA-mediated inhibition of mGluR3, GluA and GluN glutamate receptors in the dorsal striatum in wildtype mice also induces autistic-like behaviors. Optogenetic inhibition of the prelimbic cortical neurons projecting to the dorsal striatum in AC5 KO mice rescues the deficits in social and object novelty preferences. Our results suggest that AC5 mutation produces autistic-like symptoms through the upregulation of mGluR5 functions in the dorsal striatum and that the dorsal striatum regulated by AC5 is a neural correlate responsible for core ASD symptoms.

Interleukin-18 (IL18) is a multifunctional cytokine that has been implicated in increased susceptibility to depression; however, the underlying mechanism remains unknown. We found that the IL18 system in the basolateral amygdala (BLA) determined susceptibility to chronic stress. Mice subjected to chronic restraint stress or chronic foot-shock stress demonstrated increased expression of IL18 in the BLA, and exhibited depression-like behaviors, whereas IL18 knockout (KO) mice were resilient to these chronic stresses. IL18 and IL18 receptors in the BLA were expressed in glutamatergic and GABAergic neurons in addition to glial cells. Local inhibition of IL18 and IL18 receptors in the BLA by stereotaxic injection of siRNA-IL18 or siRNA-IL18 receptor-1α was sufficient to suppress stress-induced depression-like behaviors. Following chronic stress, the downstream mediator of IL18 receptor activation, phospho-NF-kB, was increased in BLA neurons expressing IL18 receptors. Furthermore, siRNA-mediated inhibition of NF-kB in the BLA significantly suppressed stress-induced depression-like behaviors, and NF-kB KO mice were resilient to chronic stress. The siRNA-mediated inhibition of NF-kB in the BLA downregulated stress-induced increased expression of Hcrt, MCH, OXT, AVP, and TRH, the neuropeptides that were induced by chronic stress in the BLA and promoted depression-like behaviors. These results suggest that the local IL18 and its receptor system in the BLA function as molecular regulators promoting susceptibility to chronic stress.

Chronic stress produces behavioral depression. Conversely, physical exercise is held to be beneficial in the treatment of depression. Although genomic mechanisms are likely involved in these behavioral changes, underlying mechanisms are not clearly understood. In the present study, we investigated whether stress effects and their reversal by exercise occur via genomic mechanisms in the amygdala, a core part of the limbic system important for regulating mood states. Mice treated with chronic restraint showed lasting depression-like behaviors, which were counteracted by treatment with scheduled forceful exercise. Microarray analysis identified a number of genes whose expression in the amygdala was either upregulated or downregulated after repeated stress, and these changes were reversed by exercise. Of these genes, the neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) were selected as representative stress-induced and exercise-responded genes in the BLA. Stereotaxic injection of OXT or AVP receptor agonists within the BLA in normal mice produced depression-like behaviors, whereas small interfering RNA (siRNA)-mediated suppression of the OXT or AVP transcripts in the BLA was sufficient to block stress-induced depressive behaviors. Stress-induced depression-like behaviors were accompanied by a global reduction of G9a histone methyltransferase and H3K9me2 at the OXT and AVP promoters. Conversely, repeated exercise increased the levels of G9a and H3K9me2 at the OXT and AVP promoters in the BLA, which was associated with the suppression of OXT and AVP expressions. These results identify G9a-induced histone methylation at the OXT and AVP promoters in the BLA as a mechanism for mediating stress-induced lasting behavioral depression and its reversal by exercise.

Purpose The purpose of this study is to evaluate the risk of sequential bilateral total knee arthroplasty (TKA) under 1 anesthesia in patients 75 years or older. Materials and methods Patients aged 75 years or older who underwent sequential bilateral TKA (bilateral group, n=159) and unilateral TKA (unilateral group, n=159) between 2002 and 2012 were selected. All patients were evaluated for underlying medical diseases, such as cardiac, pulmonary, and renal problems, and high-risk patients were recommended to postpone the surgery. We compared the underlying diseases, major postoperative complications, and the length of hospital stay between bilateral and unilateral groups. Results The prevalence of underlying diseases of the bilateral group was 74.8% and major complications occurred in 6 patients (3.8%). The prevalence of underlying diseases of the unilateral group was 52.4% and complications were observed in 4 patients (2.4%). Although the complication rate of the bilateral group was slightly higher than that of the unilateral group, the difference was not statistically meaningful (p=0.204). The length of hospital stay was 21.9 days for the bilateral group and 24.9 days for the unilateral group. Conclusions There was no significant difference in postoperative complications between groups. The result shows that bilateral TKA can be relatively safe compared with unilateral TKA in patients 75 years or older. However, careful selection of low-risk patients is advised.

Ethyl pyruvate (EP), a simple aliphatic ester of pyruvic acid, has been shown to have antiinflammatory effects and to confer protective effects in various pathological conditions. Recently, a number of studies have reported EP inhibits high mobility group box 1 (HMGB1) secretion and suggest this might contribute to its antiinflammatory effect. Since EP is used in a calcium-containing balanced salt solution (Ringer solution), we wondered if EP directly chelates Ca(2+) and if it is related to the EP-mediated suppression of HMGB1 release. Calcium imaging assays revealed that EP significantly and dose-dependently suppressed high K(+)-induced transient [Ca(2+)]i surges in primary cortical neurons and, similarly, fluorometric assays showed that EP directly scavenges Ca(2+) as the peak of fluorescence emission intensities of Mag-Fura-2 (a low-affinity Ca(2+) indicator) was shifted in the presence of EP at concentrations of ≥7 mmol/L. Furthermore, EP markedly suppressed the A23187-induced intracellular Ca(2+) surge in BV2 cells and, under this condition, A23187-induced activations of Ca(2+)-mediated kinases (protein kinase Cα and calcium/calmodulin-dependent protein kinase IV), HMGB1 phosphorylation and subsequent secretion of HMGB1 also were suppressed. (A23187 is a calcium ionophore and BV2 cells are a microglia cell line.) Moreover, the above-mentioned EP-mediated effects were obtained independent of cell death or survival, which suggests that they are direct effects of EP. Together, these results indicate that EP directly chelates Ca(2+), and that it is, at least in part, responsible for the suppression of HMGB1 release by EP.

AMI is the core infrastructure of a smart grid and it is expected to be used for many industrial fields. The components of AMI generally include a smart meter, DCU, and MDMS. In such a system, the smart meter measures power consumption and DCU collects information from smart meters and send their data to MDMS. The MDMS is an end server to get information of the power usage and store its log and data. Since there are a lot of devices such as smart meters and DCUs in AMI, it is important to maintain the suitable number of them. In particular, it is necessary to calculate the proper number of DCUs for efficient management of AMI. In this paper, we suggest a way to predict the proper number of DCUs and this proposed method is useful to predict the total performance of heterogeneous AMI. The simulation results show that AMI is greatly influenced by the difference of performance between DCUs in the heterogeneous AMI.

We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified approximately 12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.

Ti-MWW was hydrothermally synthesized employing a SiO2–TiO2 xerogel. Characterization was performed using XRD, SEM, ICP, NH3-TPD, FT-IR, UV–vis spectroscopy, and the catalytic properties of Ti-MWW was evaluated over 1-hexene epoxidation, oxidative desulfurization of model sulfur compounds, direct conversion of methanol to dimethoxymethane, and allyl chloride epoxidation using H2O2.

Neuronal activity regulates the development and maturation of excitatory and inhibitory synapses in the mammalian brain. Several recent studies have identified signalling networks within neurons that control excitatory synapse development. However, less is known about the molecular mechanisms that regulate the activity-dependent development of GABA (gamma-aminobutyric acid)-releasing inhibitory synapses. Here we report the identification of a transcription factor, Npas4, that plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes, which in turn control the number of GABA-releasing synapses that form on excitatory neurons. These findings demonstrate that the activity-dependent gene program regulates inhibitory synapse development, and suggest a new role for this program in controlling the homeostatic balance between synaptic excitation and inhibition.

Using normal canine embryonic fibroblasts (CaEF) that were shown to be senescent at passages 7th-9th, we established two spontaneously immortalized CaEF cell lines (designated CGFR-Ca-1 and -2) from normal senescent CaEF cells, and an immortal CaEF cell line by exogenous introduction of a catalytic telomerase subunit (designated CGFR-Ca-3). Immortal CGFR- Ca-1, -2 and -3 cell lines grew faster than primary CaEF counterpart in the presence of either 0.1% or 10% FBS. Cell cycle analysis demonstrated that all three immortal CaEF cell lines contained a significantly high proportion of S-phase cells compared to primary CaEF cells. CGFR-Ca-1 and -3 cell lines showed a loss of p53 mRNA and protein expression leading to inactivation of p53 regulatory function, while the CGFR-Ca-2 cell line was found to have the inactive mutant p53. Unlike the CGFR-Ca-3 cell line that down-regulated p16INK4a mRNA due to its promoter methylation but had an intact p16INK4a regulatory function, CGFR-Ca-1 and -2 cell lines expressed p16INK4a mRNA but had a functionally inactive p16INK4a regulatory pathway as judged by the lack of obvious differences in cell growth and phenotype when reconstituted with wild-type p16INK4a. All CGFR-Ca-1, -2 and -3 cell lines were shown to be untransformed but immortal as determined by anchorage-dependent assay, while these cell lines were fully transformed when overexpressed oncogenic H-rasG12V. Taken together, similar to the nature of murine embryo fibroblasts, the present study suggests that normal primary CaEF cells have relatively short in vitro lifespans and should be spontaneously immortalized at high frequency.

The purpose of this study was to evaluate CT findings of phytobezoar associated with small bowel obstruction. We evaluated abdominal CT of 19 patients with phytobezoar. Abdominal CT of 6 patients with small bowel feces was included for the comparison. On CT we analyzed morphological features of phytobezoars such as location, number, size, shape, and the presence or absence of an encapsulating wall. The sites of the phytobezoar were in the jejunum in 12 patients (63%) and the ileum in 7 (37%). The phytobezoars were single in number in 13 patients (68%) and multiple in 6 (32%). The mean short- and long-axis diameters of the phytobezoars measured 3.2 cm (range 2.1-5.2 cm) and 5.2 cm (range 2.2-11.0 cm), respectively. The phytobezoars were ovoid in 9 patients, round in 6, and tubular in 4. On CT, phytobezoars appeared as gas-containing masses in 17 patients (89%) and as a solid mass without gas in the remaining 2 patients (11%). An encapsulating wall was noted in 6 patients (32%). Small bowel feces were much more tubular in shape but did not have encapsulating wall on CT. The CT imaging is useful in making the diagnosis of phytobezoar associated with small bowel obstruction.

When parental Chinese hamster ovary (CHO) cell clones that are capable of producing thrombopoietin (TPO) were subjected to high methotrexate (MTX) concentrations, clonal variations in cell growth were apparent. In the clones that had no significant enhancement in specific TPO productivity (qTpo) when a higher level of MTX was administered, their growth was not depressed significantly nor their cell size changed significantly. On the other hand, those clones that showed a significant enhancement inqTpo at higher a MTX dosage, cell growth was depressed initially but recovered during successive sub-cultures. Furthermore, their cell size increased, which suggested that changes in cell size may be indicative of an enhancedqTpo. When the enhancement of theqTpo of 9 clones after a high MTX dosage was plotted against the extent of the increase of their size, there was a linear correlation (r2=0.80,P

Nat. Neurosci. 19, 75–83 (2016); published online 23 November 2015; corrected after print 22 January 2016 In the version of this article initially published, it was stated that the c-fos gene-based TRAP mouse line described in ref. 42 utilized only the c-fos promoter region to drive CreERT2. In fact, that line was generated by CreERT2 knock-in to the endogenous c-fos locus.

High performance poly-Si thin film transistors were fabricated by using a new crystallization method, Metal-Induced Lateral Crystallization (MILC). The process temperature was kept below 500°C throughout the fabrication. After the gate definition, thin nickel films were deposited on top of the TFT's without an additional mask, and with a one-step annealing at 500°C, the activation of the dopants in source/drain/gate a-Si films was achieved simultaneously with the crystallization of the a-Si films in the channel area. Even without a post-hydrogenation passivation, mobilities of the MILC TFT's were measured to be as high as 120cm2/Vs and 90cm2/Vs for n-channel and p-channel, respectively. These values are much higher than those of the poly-Si TFT's fabricated by conventional solid-phase crystallization at around 6001C.

Poly-Si TFT’s were fabricated on the glass substrate by the Metal Induced Lateral Crystallization(MILC). Before deposition of the active a-Si thin films(1000 Å), the glass substrate was pretreated in three different ways such as oxidation of a-Si(100 Å), oxide buffer layer deposition(1000 Å), and ion mass doping of the glass substrates. The leakage current at reverse bias could be reduced by one order of magnitude by the substrate pretreatment. Field effect mobility of n-channel TFT’s was 108cm2/Vsec, subthreshold slope and on/off current ratio were 0.7 V/dec. and about 106, respectively.

Adequate assessment of plaque deposition levels in the brain of mouse models of Alzheimer disease (AD) is required in many core issues of studies on AD, including studies on the mechanisms underlying plaque pathogenesis, identification of cellular factors modifying plaque pathology, and developments of anti-AD drugs. The present study was undertaken to quantitatively evaluate plaque deposition patterns in the brains of the two popular AD models, Tg2576 and Tg-APPswe/ PS1dE9 mice. Coronally-cut brain sections of Tg2576 and Tg-APPswe/PS1dE9 mice were prepared and plaque depositions were visualized by staining with anti- amyloid β peptides antibody. Microscopic images of plaque depositions in the prefrontal cortex, parietal cortex, piriform cortex and hippocampus were obtained and the number of plaques in each region was determined by a computer-aided image analysis method. A series of optical images representing a gradual increase of plaque deposition levels were selected in the four different brain regions and were assigned in each with a numerical grade of 1-6, where +1 was lowest and +6, highest, so that plaques per unit in mm(2) increased "sigmoidally" over the grading scales. Analyzing plaque depositions using the photographic plaque reference panels and a computer-aid image analysis method, it was demonstrated that the brains of Tg2576 mice started to accumulate predominantly small plaques, while the brains of Tg-APPswe/PS1dE9 mice deposited relatively large plaques.