Abstract
Exaggerated synaptic elimination in the prefrontal cortex (PFC) during adolescence has been suggested to contribute to the neuropathological changes of schizophrenia. Recent data indicate ...that microglia (MG) sculpt synapses during early postnatal development. However, it is not known if MG contribute to the structural maturation of the PFC, which has a protracted postnatal development. We determined if MG are involved in developmentally specific synapse elimination in the PFC, focusing on adolescence. Layer 5 PFC pyramidal cells (PCs) were intracellularly filled with Lucifer Yellow for dendritic spine measurements in postnatal day (P) 24, P30, P35, P39, and P50 rats. In the contralateral PFC we evaluated if MG engulfed presynaptic (glutamatergic) and postsynaptic (dendritic spines) elements. Dendritic spine density increased from P24 to P35, when spine density peaked. There was a significant increase in MG engulfment of spines at P39 relative to earlier ages; this subsided by P50. MG also phagocytosed presynaptic glutamatergic terminals. These data indicate that MG transiently prune synapses of PFC PCs during adolescence, when the symptoms of schizophrenia typically first appear. An increase in MG-mediated synaptic remodeling of PFC PCs may contribute to the structural changes observed in schizophrenia.
Traditional supervised learning approaches primarily work in the single-label environment. However, in many real-world problems, data instances are usually associated with multiple labels ...simultaneously, and multi-label learning is increasingly required in many modern applications. In multi-label learning, the key to successful classification is effectively exploiting the complex correlations among the output labels. This paper proposes a novel multi-label learning method inspired by the classifier chain approach. The main contribution of this work is to model the correlations of the labels using a directed acyclic graph. Starting from the simple intuitive notion of measuring the correlations among the labels, the proposed method is designed as a multi-label learning method that maximizes the correlations among labels. To evaluate its effectiveness, the proposed method is compared with the state-of-the-art approaches. Extensive experiments demonstrated the proposed method to be highly competitive with the other multi-label approaches.
In supervised learning methods, a large amount of labeled data is necessary to find reliable classification boundaries to train a classifier. However, it is hard to obtain a large amount of labeled ...data in practice and it is time-consuming with a lot of cost to obtain labels of data.
Although unlabeled data is comparatively plentiful than labeled data, most of supervised learning methods are not designed to exploit unlabeled data. Self-training is one of the semisupervised learning methods that alternatively repeat training a base classifier and labeling unlabeled data in training set. Most self-training methods have adopted confidence measures to select confidently labeled examples because high-confidence usually implies low error.
A major difficulty of self-training is the error amplification. If a classifier misclassifies some examples and the misclassified examples are included in the labeled training set, the next classifier may learn improper classification boundaries and generate more misclassified examples. Since base classifiers are built with small labeled dataset and are hard to earn good generalization performance due to the small labeled dataset. Although improving training procedure and the performance of classifiers, error occurrence is inevitable, so corrections of self-labeled data are necessary to avoid error amplification in the following classifiers. In this paper, we propose a deep neural network based approach for alleviating the problems of self-training by combining schemes: pre-training, dropout and error forgetting. By applying combinations of these schemes to various dataset, a trained classifier using our approach shows improved performance than trained classifier using common self-training KCI Citation Count: 4
Semi-supervised learning (SSL) is a method to make better models using a large number of easily accessible unlabeled data along with a small number of labeled data obtained at a high cost. Most of ...existing SSL studies focus on the cases where sufficient amount of labeled samples are available, tens to hundreds labeled samples for each class, which still requires a lot of labeling cost. In this paper, we focus on SSL environment with extremely scarce labeled samples, only 1 or 2 labeled samples per class, where most of existing methods fail to learn. We propose a propagation regularizer which can achieve efficient and effective learning with extremely scarce labeled samples by suppressing confirmation bias. In addition, for the realistic model selection in the absence of the validation dataset, we also propose a model selection method based on our propagation regularizer. The proposed methods show 70.9%, 30.3%, and 78.9% accuracy on CIFAR-10, CIFAR-100, SVHN dataset with just one labeled sample per class, which are improved by 8.9% to 120.2% compared to the existing approaches. And our proposed methods also show good performance on a higher resolution dataset, STL-10.
Inactive cortisone is converted into active cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function; barrier ...impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11β-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11β-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11β-HSD1 knockout mice (n = 11), 11β-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11β-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels; this effect was reversed by INHI treatment. Therefore, upregulation of 11β-HSD1 in the aged skin increases the active-glucocorticoid levels; this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier.
Increased endothelial permeability is central to the pathogenesis of sepsis and leads to organ dysfunction and death but the endogenous mechanisms that drive increased endothelial permeability are ...not completely understood. We previously reported that cell-free hemoglobin (CFH), elevated in 80% of patients with sepsis, increases lung microvascular permeability in an ex vivo human lung model and cultured endothelial cells. In this study, we augmented a murine model of polymicrobial sepsis with elevated circulating CFH to test the hypothesis that CFH increases microvascular endothelial permeability by inducing endothelial apoptosis. Mice were treated with an intraperitoneal injection of cecal slurry with or without a single intravenous injection of CFH. Severity of illness, mortality, systemic and lung inflammation, endothelial injury and dysfunction and lung apoptosis were measured at selected time points. We found that CFH added to CS increased sepsis mortality, plasma inflammatory cytokines as well as lung apoptosis, edema and inflammation without affecting large vessel reactivity or vascular injury marker concentrations. These results suggest that CFH is an endogenous mediator of increased endothelial permeability and apoptosis in sepsis and may be a promising therapeutic target.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long‐standing or repeated skin barrier damage followed by atopic dermatitis (AD) is the initial step of the atopic march that eventually progresses to respiratory allergies. Maintenance of an acidic ...pH in the stratum corneum (SC) is an important factor for normal skin barrier function. We performed this study to determine whether an oxazolone (Ox)‐induced AD murine model can develop airway inflammation by topical application and nasal inhalation of a house dust mite, Dermatofagoides pteronyssinus (Dp), which is a novel ‘atopic march animal model’, and whether an acidic SC environment, made by repeated application of acidic cream, can interrupt this atopic march. During repeated treatment with Ox and Dp to make an atopic march murine model, acidic cream (pH 2.8) and neutral cream (pH 7.4) adjusted by citric acid and sodium hydroxide mixed with vehicle were applied twice daily. Repeated treatment with Ox and Dp to hairless mice induced AD‐like skin lesions followed by respiratory allergy, defining it as an atopic march model. Acidic cream inhibited the occurrence of respiratory allergic inflammation as well as AD‐like skin lesions. These results indicate that a novel atopic march animal model can be developed by repeated topical and nasal treatments with house dust mite on Ox‐induced AD mice and that the acidification of SC could be a novel intervention method to block the atopic march.
Prolonged and/or repeated damage to the skin barrier followed by atopic dermatitis (AD) is an initial step in atopic march that ultimately progresses to respiratory allergy. Maintaining normal ...stratum corneum (SC) acidity has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. We determined whether a representative AD murine model, NC/Nga mice, develops airway inflammation after repeated epicutaneous application followed by inhalation of house dust mite (HDM), implying atopic march, and whether prolongation of non-proper SC acidity accelerates respiratory allergy. HDM was applied to the skin of NC/Nga mice, accompanied by the application of neutral cream (pH 7.4) or acidic cream (pH 2.8) for 6weeks. Intranasal inhalation of HDM was administered daily during the last 3days. Repeated epicutaneous applications followed by inhalation of HDM in NC/Nga mice induced an atopic march-like progression from AD lesions to respiratory allergy. Concurrent neutral cream treatment accelerated or aggravated the allergic inflammation in the skin and respiratory system, whereas an acidic cream partially alleviated these symptoms. Collectively, we developed an atopic march in NC/Nga mice by HDM application, and found that prevention of a neutral environment in the SC may be an interventional method to inhibit the march.
Alopecia areata (AA) affects anagen hair follicles, resulting in non‐scarring hair loss. Since introduced by Huang et al., superficial cryotherapy has been accepted as a considerable primary ...therapeutic modality for AA. The aim of this study was to objectively clarify the therapeutic efficacy and safety of superficial hypothermic cryotherapy for treatment of AA. Medical records of 353 patients from 1993 to 2014 were retrospectively analyzed. According to the response to the superficial cryotherapy, patients were categorized into four groups: “marked”, “partial”, “poor” and “no recovery”. The marked and partial recovery groups were considered as responders. The proportions of the responders among patient subgroups which were defined by various patients, disease, and treatment factors were compared. Of the patients, 60.9% were classified as responders after 3 months of superficial hypothermic cryotherapy. The proportion of the responders were higher when the treatment interval was 2 weeks or less and in the incipient disease stage, with statistical significance. No severe side‐effects other than mild pain and pruritus were reported. In conclusion, superficial cryotherapy is an effective and safe therapeutic modality for AA. Especially when the treatment interval is 2 weeks or less and in the first occurrence of the disease, the therapeutic outcome is superior.
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