Utilizing an Animal Model to Identify Brain Neurodegeneration-Related Biomarkers in Aging

Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAMe), a methyl donor in methylation. Over-expressed SAMe may cause neurogenic capacity reduction and memory impairment. GNMT knockout mice (GNMT-KO) was applied as an experimental model to evaluate its effect on neurons. In this study, proteins from brain tissues were studied using proteomic approaches, Haemotoxylin and Eosin staining, immunohistochemistry, Western blotting, and ingenuity pathway analysis. The expression of Receptor-interacting protein 1(RIPK1) and Caspase 3 were up-regulated and activity-dependent neuroprotective protein (ADNP) was down-regulated in GNMT-KO mice regardless of the age. Besides, proteins related to neuropathology, such as excitatory amino acid transporter 2, calcium/calmodulin-dependent protein kinase type II subunit alpha, and Cu-Zn superoxide dismutase were found only in the group of aged wild-type mice; 4-aminobutyrate amino transferase, limbic system-associated membrane protein, sodium- and chloride-dependent GABA transporter 3 and ProSAAS were found only in the group of young GNMT-KO mice and are related to function of neurons; serum albumin and Rho GDP dissociation inhibitor 1 were found only in the group of aged GNMT-KO mice and are connected to neurodegenerative disorders. With proteomic analyses, a pathway involving Gonadotropin-releasing hormone (GnRH) signal was found to be associated with aging. The GnRH pathway could provide additional information on the mechanism of aging and non-aging related neurodegeneration, and these protein markers may be served in developing future therapeutic treatments to ameliorate aging and prevent diseases.     

MEMS-based gas flow sensors

Micro-electro-mechanical system (MEMS) devices integrate various mechanical elements, sensors, actuators, and electronics on a single silicon substrate in order to accomplish a multitude of different tasks in a diverse range of fields. The potential for device miniaturization made possible by MEMS micro-fabrication techniques has facilitated the development of many new applications, such as highly compact, non-invasive pressure sensors, accelerometers, gas sensors, etc. Besides their small physical footprint, such devices possess many other advantages compared to their macro-scale counterparts, including greater precision, lower power consumption, more rapid response, and the potential for low-cost batch production. One area in which MEMS technology has attracted particular attention is that of flow measurement. Broadly speaking, existing micro-flow sensors can be categorized as either thermal or non-thermal, depending upon their mode of operation. This paper commences by providing a high level overview of the MEMS field and then describes some of the fundamental thermal and non-thermal micro-flow sensors presented in the literature over the past 30 years or so.     

Experimental and numerical investigation into the joule heating effect for electrokinetically driven microfluidic chips utilizing total internal reflection fluorescence microscopy

This paper presents a detection scheme for analyzing the temperature distribution nearby the channel wall in a microfluidic chip utilizing a temperature-dependent fluorescence dye. An advanced optical microscope system—total internal reflection fluorescence microscope (TIRFM) is used for measuring the temperature distribution on the channel wall at the point of electroosmotic flow in an electrokinetically driven microfluidic chip. In order to meet the short working distance of the objective type TIRFM scheme, microscope cover glass slits are used to fabricate the microfluidic chips. The short fluorescence excitation depth from a TIRFM system makes the intensity information obtained using TIRFM is not sensitive to the channel depth variation which ususally biases the measured results while using a conventional Epi-fluorescence microscope (EPI-FM). Therefore, a TIRFM can precisely describe the temperature profile of the distance within 100 nm of the channel wall where consists of the Stern layer and the diffusion layer for an electrokinetic microfluidic system. Results indicate the proposed TIRFM provides higher measurement sensitivity over the EPI-FM. Significant temperature gradient along the channel depth is experimentally observed. In addition, the measured wall temperature distributions can be the boundary conditions for numerical investigation into the joule heating effect. The proposed method gives a precise temperature profile of microfluidic channels and shows the substantial impact on developing a numerical simulation model for precisely predicting the joule heating effect in microfluidic chips.     

MEMS-based formaldehyde gas sensor integrated with a micro-hotplate

This paper presents a novel micro-fabricated formaldehyde gas sensor with enhanced sensitivity and detection resolution capabilities. The device comprises a quartz substrate with Pt heaters as a micro-hotplate and deposited formaldehyde-sensing layer on it. A sputtered NiO thin film is used as the formaldehyde-sensing layer. A specific orientation of NiO becomes more apparent as the substrate temperature increases in the sputtering process, which helps the formation of NiO material with a correct stoichiometric ratio. The gas sensor incorporates Pt heating resistors integrated with a micro-hotplate to provide a heating function and utilizes Au inter-digitated electrodes. When formaldehyde is present in the atmosphere, oxydation happens near the sensing layer with a high temperature caused by the micro-hotplate and causes a change in the electrical conductivity of the NiO film. Therefore, the measured resistance between the inter-digitated electrodes changes correspondingly. The application of a voltage to the Pt heaters causes the temperature of the micro-hotplate to increase, which in turn enhances the sensitivity of the sensor. The nanometer scale grain size of the sputtered oxide thin film is conducive to improving the sensitivity of the gas sensor. The experimental results indicate that the developed device has a high stability (0.23%), a low hysteresis value (0.18%), a quick response time (13.0 s), a high degree of sensitivity (0.14 Ω ppm⁻¹), and a detection capability of less than 1.2 ppm.

     

The impact of physiographic factors upon the probability of slides occurrence: a case study from the Kaoping River Basin,Taiwan

This study has investigated the influence of physiographic factors upon the probability of slide occurrence in the Kaoping River Basin. According to previous literature, statistical tests, and physical mechanisms, three physiographic factors (slope steepness, the dip slope ratio, and the time-dependent landslide ratio) were significantly related to slide occurrence. These were combined with hydrological factors (cumulative rainfall) to establish an assessment model for estimating the probability of slide occurrence using logistic regression. The model’s overall accuracy in the training and validation stages was about 81%. Overall, 20 randomly selected historical rainfall events were employed for verification, including 10 events each with and without slide occurrence. The results showed that the model accuracy was approximately 80%, if the probability threshold P_sh is set to be 0.5.

This assessment model can assist in prediction of slide occurrence and the proposed subsequent engineering measures or vegetation restoration is often able to reduce the landslide ratio and the probability of slide occurrence. After landform changes, the model’s physiographic factors can be updated to adjust the rainfall threshold for slide occurrence. Given an appropriate cumulative rainfall and an acceptable risk of slide occurrence, the model can identify priority regions for slide prevention.     

Enhanced sensing characteristics in MEMS-based formaldehyde gas sensors

This paper presents a novel micro fabrication for formaldehyde gas sensors to enhance sensitivity and detection resolution capabilities. Therefore, two different types of fabrication sequences of gas sensors were considered, different positions of micro heaters and sensing layers to compare the effects of different areas of the sensing layers contact with the surrounding gas. The MEMS-based formaldehyde gas sensor consists of a quartz substrate, a thin-film NiO/Al₂O₃ sensing layer, an integrated Pt micro-hotplate, and Pt inter-digitized electrodes (IDEs) to measure the resistance variation of sensing layers caused by formaldehyde oxidation at the oxide surface. This abstract offers comparisons of the characteristics of sensors in different areas of the sensing layers contacting the surrounding gas as well as those to decrease the thickness of the sensing layer and deposits of the sensing layer using co-sputtering technology with NiO/Al₂O₃ to improve the sensitivity limits of the sensors. The experimental data indicated that increasing the area of the sensing layer that contacts with the surrounding gas and decreasing the thickness of the sensing layer in the sputtering process and then co-sputtered NiO/Al₂O₃ sensing layers, significantly enhanced the sensing characteristics of the developed formaldehyde sensor.     

Electrophoresis separation and electrochemical detection on a novel thread-based microfluidic device

This paper describes a thread-based microfluidic system for rapid and low-cost electrophoresis separation and electrochemical (EC) detection of ion samples. Instead of using liquid channel for sample separation, thin polyester threads of various diameters are used as the routes for separating the samples with electrophoresis. Hot-pressed PMMA chip with protruding sleeper structures are adopted to set up the polyester threads and for electrochemical detection of the ion samples on the thread. Plasma treatment greatly improves the wetability of thin threads and surface quality of the threads. The measured electrical currents on plasma treated threads are 10 times greater than the threads without treatment. Results indicate that nice redox signals can be obtained by measuring ferric cyanide salt on the polyester thread. The estimated detection limit for EC sensing of potassium ferricyanide (K₃Fe(CN)₆) is around 6.25 μM using the developed thread-based microfluidic device. Mixed ion samples (Cl^?, Br^? and I^?) and bio-sample are successfully separated and detected using the developed thread-based microfluidic device.     

CD8+ T Cell-Induced Expression of Tissue Inhibitor of Metalloproteinses-1 Exacerbated Osteoarthritis

Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8⁺ T cells in this disease. We investigated the effects of CD8⁺ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate ligament-transection (ACLT), OA was induced in mice. The knee joints were histologically assessed for manifestations of OA. The CD8⁺ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and VEGF were examined. Cartilage degeneration was slower in CD8⁺ T cell knockout mice than in control mice. CD8⁺ T cells were activated once OA was initiated and expanded during OA progression. More CD8⁺ T cells from splenocytes expressed TIMP-1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing CD8⁺ T cells in OA mice correlated with the disease severity. TIMP-1 expression in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was detected in synovium in which angiogenesis occurred. During the pathogenesis of OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8⁺ T cells activation were increased. Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA.     

Capabilities and limitations of 2-dimensional and 3-dimensional numerical methods in modeling the fluid flow in sudden expansion microchannels

This paper deals with computational and experimental investigations into pressure-driven flow in sudden expansion microfluidic channels. Improving the design and operation of microfluidic systems requires that the capabilities and limitations of 2-dimensional (2-D) and 3-dimensional (3-D) numerical methods in simulating the flow field in a sudden expansion microchannel be well understood. The present 2-D simulation results indicate that a flow separation vortex forms in the corner behind the sudden expansion microchannel when the Reynolds number is very low (Re∼0.1). However, the experimental results indicate that this prediction is valid only in the case of a sudden expansion microchannel with a high aspect ratio (aspect ratio >> 1). 3-D computational fluid dynamics simulations are performed to predict the critical value of Re at which the flow separation vortex phenomenon is induced in sudden expansion microchannels of different aspect ratios. The experimental flow visualization results are found to be in good agreement with the 3-D numerical predictions. The present results provide designers with a valuable guideline when choosing between 2-D or 3-D numerical simulations as a means of improving the design and operation of microfluidic devices.