Paper-Based ELISA: A Novel Diagnostic Approach for Monitoring Aqueous Humour VEGF Level in Ocular Diseases

We commonly diagnose ocular diseases via both morphological changes and symptoms. It is necessary to develop biochemically based assays for early or follow-up diagnosis of these diseases with a focus on robustness and ease of handling. To lay out a prospective path toward this goal, we describe and propose the use of ultrahigh sensitive paper-based ELISA (p-ELISA), which uses a treated piece of filter paper to monitor the activity of ocular diseases (i.e., detecting the vascular endothelial growth factor (VEGF) concentration in aqueous humour for proliferative diabetic retinopathy or age-related macular degeneration diagnosis). The advantages of p-ELISA include the following: (1) the capacity to directly measure biomarker concentrations in aqueous humour using only a tiny sample volume (as little as 2 μL); (2) significantly increased sensitivity compared to conventional ELISA (fg/mL levels); and (3) inexpensive materials and a short operation duration. P-ELISA is a novel point-of-care diagnostic tool with the significant potential to advance ophthalmological treatment guidelines by facilitating early detection and routinely monitoring therapeutic response

Optimizing mixture properties of biodiesel production using genetic algorithm-based evolutionary support vector machine

Nowadays, biodiesel is used as one of the alternative renewable energy due to the increasing energy demand. However, optimum production of biodiesel still requires a huge number of expensive and time-consuming laboratory tests. To address the problem, this research develops a novel Genetic Algorithm-based Evolutionary Support Vector Machine (GA-ESIM). The GA-ESIM is an Artificial Intelligence (AI)-based tool that combines K-means Chaotic Genetic Algorithm (KCGA) and Evolutionary Support Vector Machine Inference Model (ESIM). The ESIM is utilized as a supervised learning technique to establish a highly accurate prediction model between the input--output of biodiesel mixture properties; and the KCGA is used to perform the simulation to obtain the optimum mixture properties based on the prediction model. A real biodiesel experimental data is provided to validate the GA-ESIM performance. Our simulation results demonstrate that the GA-ESIM establishes a prediction model with better accuracy than other AI-based tool and thus obtains the mixture properties with the biodiesel yield of 99.9%, higher than the best experimental data record, 97.4%

Exploring Individuals’ Loyalty To Online Support Groups From the Perspective Of Social Support

Prior research indicates that social support allows individuals to have additional skills to handle stresses, enhance self-esteem, and increase psychological well-being. Online social networks have become an emerging and important source of social support. However, little research has been done to explore how IT usage may improve the well-being and life quality of individuals, especially patients. Little research has been done to empirically examine individuals’ loyalty toward online social groups from the perspective of social support. This study aims to develop an integrated research model to the impact of online social support on psychological well-being and group identification, and individuals’ subsequent loyalty toward online social groups. Online social support group was operationalized as a second-order construct with four components: informational, emotional, esteem, and network supports. Data collected from 537 users of online support groups for mothers in Taiwan provide strong support for the research model. The results indicate that online social support is positively associated with psychological well-being and group identification, which in turn have a positive effect on moms’ loyalty toward online social groups. Implications for theory and practice and suggestions for future research are provided

Infectious Alopecia in a Dog Breeder After Renal Transplantation

Tinea capitis rarely occurs in renal transplant recipients. We report this living-related renal transplant patient receiving cyclosporine-based therapy who initially presented with severe exfoliation of the scalp with yellowish-white scales and marked hair loss. The lesions extended to the frontal area and both cheeks, resulting in several skin ulcers with perifocal erythematous inflammatory changes, and palpable cervical lymph nodes. A biopsy of a skin lesion revealed fungal infection and culture yielded Microsporum canis. The patient mentioned an outbreak of ringworm in her breeding dogs during this period. After adequate treatment of the patient and her infected animals with griseofulvin and disinfection of the environment, her skin lesions resolved dramatically, with regrowth of hair

Genetic and Functional Analysis of the DLG4 Gene Encoding the Post-Synaptic Density Protein 95 in Schizophrenia

Hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated signal transduction has been implicated in the pathophysiology of schizophrenia. Post-synaptic density protein 95 (PSD95) plays a critical role in regulating the trafficking and activity of the NMDA receptor and altered expression of the PSD95 has been detected in the post-mortem brain of patients with schizophrenia. The study aimed to examine whether the DLG4 gene that encodes the PSD95 may confer genetic susceptibility to schizophrenia. We re-sequenced the core promoter, all the exons, and 3′ untranslated regions (UTR) of the DLG4 gene in 588 Taiwanese schizophrenic patients and conducted an association study with 539 non-psychotic subjects. We did not detect any rare mutations at the protein-coding sequences of the DLG4 gene associated with schizophrenia. Nevertheless, we identified four polymorphic markers at the core promoter and 5′ UTR and one single nucleotide polymorphism (SNP) at the 3′UTR of the DLG4 gene in this sample. Genetic analysis showed an association of a haplotype (C–D) derived from 2 polymorphic markers at the core promoter (odds ratio = 1.26, 95% confidence interval = 1.06–1.51, p = 0.01), and a borderline association of the T allele of the rs13331 at 3′UTR with schizophrenia (odds ratio = 1.19, 95% confidence interval = 0.99–1.43, p = 0.06). Further reporter gene assay showed that the C-D-C-C and the T allele of the rs13331 had significant lower activity than their counter parts. Our data indicate that the expression of the DLG4 gene is subject to regulation by the polymorphic markers at the core promoter region, 5′ and 3′UTR of the gene, and is associated with the susceptibility of schizophrenia

Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane

We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer

以數值方法探討卵礫石層的力學行為

Gravel formation involves the mixture of hard gravel and a soil matrix. Knowing the integrated mechanical characteristics of gravel formation is beneficial for engineering constructions and disaster prevention. This study adopts the software PFC2D, which is based on the discrete element method, to investigate the mechanical behavior of gravel formations. First, simulation is carried out through a biaxial test to adjust the micro parameters in PFC2D, and then multiple regression analysis is performed to establish the relationship between macro and micro parameters. Furthermore, with the reasonable micro parameters obtained, the particle size and content of gravel can changed to investigate how they influence mechanical behavior. The results show that the bigger particle size and the greater the content of gravel, the higher the values of shear strength, elastic modulus, Poisson’s ratio and friction angle, but the lower the value of cohesion. In other words, this kind of material has higher shear strength and stronger deformation resistance. These findings correspond with previous research results.卵礫石層是混合堅硬卵礫石與基質土壤之綜合體，了解卵礫石層整體力學性質，對工程建設與災害防治有極大幫助。本研究以台灣中部卵礫石層為對象，運用分離元素法為基礎之軟體PFC2D 探討卵礫石材料力學行為。首先進行雙軸試驗之模擬，校正PFC2D 微觀參數，接著利用複迴歸分析 (multiple regression model)建立宏觀參數與微觀參數間之關係。另外，以得到的合理微觀參數，改變卵礫石粒徑大小與含量，探討粒徑大小和含量對力學性質的影響。結果顯示當卵礫石粒徑越大與含量越多，其剪力強度、彈性模數、柏松比、摩擦角也會越大，但凝聚力略為下降。表示卵礫石粒徑大、含量高之材料，其抗剪強度大，變形性小，此結果與前人研究結果相符

Mediation of Endogenous β-endorphin by Tetrandrine to Lower Plasma Glucose in Streptozotocin-induced Diabetic Rats

The role of β-endorphin in the plasma glucose-lowering action of tetrandrine in streptozotocin-induced diabetic rats (STZ-diabetic rats) was investigated. The plasma glucose concentration was assessed by the glucose oxidase method. The enzyme-linked immunosorbent assay was used to determine the plasma level of β-endorphin-like immunoreactivity (BER). The mRNA levels of glucose transporter subtype 4 (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats were detected by Northern blotting analysis. The expressed protein of GLUT4 or PEPCK was characterized by Western blotting analysis. Tetrandrine dose-dependently increased plasma BER in a manner parallel to the decrease of plasma glucose in STZ-diabetic rats. Moreover, the plasma glucose-lowering effect of tetrandrine was inhibited by naloxone and naloxonazine at doses sufficient to block opioid μ-receptors. Further, tetrandrine failed to produce plasma glucose-lowering action in opioid μ-receptor knockout diabetic mice. Bilateral adrenalectomy eliminated the plasma glucose-lowering effect and plasma BER-elevating effect of tetrandrine in STZ-diabetic rats. Both effects were abolished by treatment with hexamethonium or pentolinium at doses sufficient to block nicotinic receptors. Tetrandrine enhanced BER release directly from the isolated adrenal medulla of STZ-diabetic rats and this action was abolished by the blockade of nicotinic receptors. Repeated intravenous administration of tetrandrine (1.0 mg/kg) to STZ-diabetic rats for 3 days resulted in an increase in the mRNA and protein levels of the GLUT4 in soleus muscle, in addition to the lowering of plasma glucose. Similar treatment with tetrandrine reversed the elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. The obtained results suggest that tetrandrine may induce the activation of nicotinic receptors in adrenal medulla to enhance the secretion of β-endorphin, which could stimulate opioid μ-receptors to increase glucose utilization or/and reduce hepatic gluconeogenesis to lower plasma glucose levels in STZ-diabetic rats

Intra- and Inter-Individual Variance of Gene Expression in Clinical Studies

BACKGROUND: Variance in microarray studies has been widely discussed as a critical topic on the identification of differentially expressed genes; however, few studies have addressed the influence of estimating variance. METHODOLOGY/PRINCIPAL FINDINGS: To break intra- and inter-individual variance in clinical studies down to three levels--technical, anatomic, and individual--we designed experiments and algorithms to investigate three forms of variances. As a case study, a group of "inter-individual variable genes" were identified to exemplify the influence of underestimated variance on the statistical and biological aspects in identification of differentially expressed genes. Our results showed that inadequate estimation of variance inevitably led to the inclusion of non-statistically significant genes into those listed as significant, thereby interfering with the correct prediction of biological functions. Applying a higher cutoff value of fold changes in the selection of significant genes reduces/eliminates the effects of underestimated variance. CONCLUSIONS/SIGNIFICANCE: Our data demonstrated that correct variance evaluation is critical in selecting significant genes. If the degree of variance is underestimated, "noisy" genes are falsely identified as differentially expressed genes. These genes are the noise associated with biological interpretation, reducing the biological significance of the gene set. Our results also indicate that applying a higher number of fold change as the selection criteria reduces/eliminates the differences between distinct estimations of variance

A protein interaction based model for schizophrenia study

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a complex disease with multiple factors contributing to its pathogenesis. In addition to environmental factors, genetic factors may also increase susceptibility. In other words, schizophrenia is a highly heritable disease. Some candidate genes have been deduced on the basis of their known function with others found on the basis of chromosomal location. Individuals with multiple candidate genes may have increased risk. However it is not clear what kind of gene combinations may produce the disease phenotype. Their collective effect remains to be studied.</p> <p>Results</p> <p>Most pathways except metabolic pathways are rich in protein-protein interactions (PPIs). Thus, the PPI network contains pathway information, even though the upstream-downstream relation of PPI is yet to be explored. Here we have constructed a PPI sub-network by extracting the nearest neighbour of the 36 reported candidate genes described in the literature. Although these candidate genes were discovered by different approaches, most of the proteins formed a cluster. Two major protein interaction modules were identified on the basis of the pairwise distance among the proteins in this sub-network. The large and small clusters might play roles in synaptic transmission and signal transduction, respectively, based on gene ontology annotation. The protein interactions in the synaptic transmission cluster were used to explain the interaction between the NRG1 and CACNG2 genes, which was found by both linkage and association studies. This working hypothesis is supported by the co-expression analysis based on public microarray gene expression.</p> <p>Conclusion</p> <p>On the basis of the protein interaction network, it appears that the NRG1-triggered NMDAR protein internalization and the CACNG2 mediated AMPA receptor recruiting may act together in the glutamatergic signalling process. Since both the NMDA and AMPA receptors are calcium channels, this process may regulate the influx of Ca²⁺. Reducing the cation influx might be one of the disease mechanisms for schizophrenia. This PPI network analysis approach combined with the support from co-expression analysis may provide an efficient way to propose pathogenetic mechanisms for various highly heritable diseases.</p