The Anorexic Effect of DL-fenfluramine is Dependent on Animals\u27 Habituation to Different Food Types

Background: As rates of obesity and diabetes have increased dramatically over the past few decades, the use of anti-obesity drugs has now become a routine therapeutic measure. However, the pharmacological effects of chronic use of these drugs in humans frequently lead to reduced efficacy in reducing appetite and body weight through as-yet-unidentified mechanisms. An example of this can be found in animal studies where the appetite suppressant DL-fenfluramine (FEN) is chronically administered and its tolerance develops in animals and humans. The appetite effects of FEN are typically measured in several animal studies by the feeding changes in a balanced standard diet. To determine whether FEN differentially altered appetite suppression in animals with long-term expression with different macronutrient diet compositions, its anorexic effects were measured specifically in male rats that had previously been chronically maintained on normal chow (NC) or a high-fat and high-carbohydrate western diet (WD). Methods: Three experiments were conducted by feeding the animals either NC or WD for 1 month to habituate them with their diet. Animals maintained on either NC or WD were subsequently offered both diet options ad libitum for a 2- or 7-day adaptation period while receiving daily systemic FEN treatment. Results: The results suggested that long-term habituated food affected the food preference of animals and their appetite even after chronic systemic FEN administration. Therefore, the effectiveness and success or failure of repeated use of chronic anti-obesity drugs may depend on habituated food type. Conclusion: The appetite suppressant effect was found to be determined by the palatability of a specific macronutrient and the habituated food rather than by a change in the concentration of the administered FEN. This results in a critical analysis of the rationale for taking medication considering the patient\u27s past dietary habits to achieve successful weight loss

Vision based interface system for hands free control of an intelligent wheelchair

<p>Abstract</p> <p>Background</p> <p>Due to the shift of the age structure in today's populations, the necessities for developing the devices or technologies to support them have been increasing. Traditionally, the wheelchair, including powered and manual ones, is the most popular and important rehabilitation/assistive device for the disabled and the elderly. However, it is still highly restricted especially for severely disabled. As a solution to this, the Intelligent Wheelchairs (IWs) have received considerable attention as mobility aids. The purpose of this work is to develop the IW interface for providing more convenient and efficient interface to the people the disability in their limbs.</p> <p>Methods</p> <p>This paper proposes an intelligent wheelchair (IW) control system for the people with various disabilities. To facilitate a wide variety of user abilities, the proposed system involves the use of face-inclination and mouth-shape information, where the direction of an IW is determined by the inclination of the user's face, while proceeding and stopping are determined by the shapes of the user's mouth. Our system is composed of electric powered wheelchair, data acquisition board, ultrasonic/infra-red sensors, a PC camera, and vision system. Then the vision system to analyze user's gestures is performed by three stages: detector, recognizer, and converter. In the detector, the facial region of the intended user is first obtained using Adaboost, thereafter the mouth region is detected based on edge information. The extracted features are sent to the recognizer, which recognizes the face inclination and mouth shape using statistical analysis and <it>K</it>-means clustering, respectively. These recognition results are then delivered to the converter to control the wheelchair.</p> <p>Result & conclusion</p> <p>The advantages of the proposed system include 1) accurate recognition of user's intention with minimal user motion and 2) robustness to a cluttered background and the time-varying illumination. To prove these advantages, the proposed system was tested with 34 users in indoor and outdoor environments and the results were compared with those of other systems, then the results showed that the proposed system has superior performance to other systems in terms of speed and accuracy. Therefore, it is proved that proposed system provided a friendly and convenient interface to the severely disabled people.</p

Quantum Simulation of Dissipative Energy Transfer via Noisy Quantum Computer

In recent years, due to its formidable potential in computational theory, quantum computing has become a very popular research topic. However, the implementation of practical quantum algorithms, which hold the potential to solve real-world problems, is often hindered by the significant error rates associated with quantum gates and the limited availability of qubits. In this study, we propose a practical approach to simulate the dynamics of an open quantum system on a noisy computer, which encompasses general and valuable characteristics. Notably, our method leverages gate noises on the IBM-Q real device, enabling us to perform calculations using only two qubits. The results generated by our method performed on IBM-Q Jakarta aligned with the those calculated by hierarchical equations of motion (HEOM), which is a classical numerically-exact method, while our simulation method runs with a much better computing complexity. In the last, to deal with the increasing depth of quantum circuits when doing Trotter expansion, we introduced the transfer tensor method(TTM) to extend our short-term dynamics simulation. Based on quantum simulator, we show the extending ability of TTM, which allows us to get a longer simulation using a relatively short quantum circuits

Advancing the early detection of canine cognitive dysfunction syndrome with machine learning-enhanced blood-based biomarkers

Up to half of the senior dogs suffer from canine cognitive dysfunction syndrome (CCDS), the diagnosis method relies on subjective questionnaires such as canine cognitive dysfunction rating (CCDR) scores. Therefore, the necessity of objective diagnosis is emerging. Here, we developed blood-based biomarkers for CCDS early detection. Blood samples from dogs with CCDR scores above 25 were analyzed, and the biomarkers retinol-binding protein 4 (RBP4), C-X-C-motif chemokine ligand 10 (CXCL10), and NADPH oxidase 4 (NOX4) were validated against neurodegenerative models. Lower biomarker levels were correlated with higher CCDR scores, indicating cognitive decline. Machine-learning analysis revealed the highest predictive accuracy when analyzing the combination of RBP4 and NOX4 using the support vector machine algorithm and confirmed potential diagnostic biomarkers. These results suggest that blood-based biomarkers can notably improve CCDS early detection and treatment, with implications for neurodegenerative disease management in both animals and humans

Ordinary kriging approach to predicting long-term particulate matter concentrations in seven major Korean cities

Objectives Cohort studies of associations between air pollution and health have used exposure prediction approaches to estimate individual-level concentrations. A common prediction method used in Korean cohort studies is ordinary kriging. In this study, performance of ordinary kriging models for long-term particulate matter less than or equal to 10 μm in diameter (PM10) concentrations in seven major Korean cities was investigated with a focus on spatial prediction ability. Methods We obtained hourly PM10 data for 2010 at 226 urban-ambient monitoring sites in South Korea and computed annual average PM10 concentrations at each site. Given the annual averages, we developed ordinary kriging prediction models for each of the seven major cities and for the entire country by using an exponential covariance reference model and a maximum likelihood estimation method. For model evaluation, cross-validation was performed and mean square error and R-squared (R2) statistics were computed. Results Mean annual average PM10 concentrations in the seven major cities ranged between 45.5 and 66.0 μg/m3 (standard deviation=2.40 and 9.51 μg/m3, respectively). Cross-validated R2 values in Seoul and Busan were 0.31 and 0.23, respectively, whereas the other five cities had R2 values of zero. The national model produced a higher crossvalidated R2 (0.36) than those for the city-specific models. Conclusions In general, the ordinary kriging models performed poorly for the seven major cities and the entire country of South Korea, but the model performance was better in the national model. To improve model performance, future studies should examine different prediction approaches that incorporate PM10 source characteristics

Synthesis and structure-activity relationship studies of novel 3,9-substituted α-carboline derivatives with high cytotoxic activity against colorectal cancer cells

In our continued focus on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesized a novel series of 3,9-substituted α-carboline derivatives and evaluated the new compounds for antiproliferactive effects. Structure activity relationships revealed that a COOCH or CHOH group at position-3 and substituted benzyl group at position-9 of the α-carboline nucleus were crucial for maximal activity. The most active compound, , showed high levels of cytotoxicity against HL-60, COLO 205, Hep 3B, and H460 cells with IC values of 0.3, 0.49, 0.7, and 0.8 μM, respectively. The effect of compound on the cell cycle distribution demonstrated G2/M arrest in COLO 205 cells. Furthermore, mechanistic studies indicated that compound induced apoptosis by activating death receptor and mitochondria dependent apoptotic signaling pathways in COLO 205 cells. The new 3,9-substituted α-carboline derivatives exhibited excellent anti-proliferative activities, and compound can be used as a promising pro-apoptotic agent for future development of new antitumor agents

c-Jun NH2-terminal kinase-dependent upregulation of DR5 mediates cooperative induction of apoptosis by perifosine and TRAIL

<p>Abstract</p> <p>Background</p> <p>Perifosine, an alkylphospholipid tested in phase II clinical trials, modulates the extrinsic apoptotic pathway and cooperates with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to augment apoptosis. The current study focuses on revealing the mechanisms by which perifosine enhances TRAIL-induced apoptosis.</p> <p>Results</p> <p>The combination of perifosine and TRAIL was more active than each single agent alone in inducing apoptosis of head and neck squamous cell carcinoma cells and inhibiting the growth of xenografts. Interestingly, perifosine primarily increased cell surface levels of DR5 although it elevated the expression of both DR4 and DR5. Blockade of DR5, but not DR4 upregulation, via small interfering RNA (siRNA) inhibited perifosine/TRAIL-induced apoptosis. Perifosine increased phosphorylated c-Jun NH₂-terminal kinase (JNK) and c-Jun levels, which were paralleled with DR4 and DR5 induction. However, only DR5 upregulaiton induced by perifosine could be abrogated by both the JNK inhibitor SP600125 and JNK siRNA. The antioxidants, N-acetylcysteine and glutathione, but not vitamin C or tiron, inhibited perifosine-induced elevation of p-c-Jun, DR4 and DR5. Moreover, no increased production of reactive oxygen species was detected in perifosine-treated cells although reduced levels of intracellular GSH were measured.</p> <p>Conclusions</p> <p>DR5 induction plays a critical role in mediating perifosine/TRAIL-induced apoptosis. Perifosine induces DR5 expression through a JNK-dependent mechanism independent of reactive oxygen species.</p

The complete chloroplast genome sequence of Abies nephrolepis (Pinaceae: Abietoideae)

AbstractThe plant chloroplast (cp) genome has maintained a relatively conserved structure and gene content throughout evolution. Cp genome sequences have been used widely for resolving evolutionary and phylogenetic issues at various taxonomic levels of plants. Here, we report the complete cp genome of Abies nephrolepis. The A. nephrolepis cp genome is 121,336 base pairs (bp) in length including a pair of short inverted repeat regions (IRa and IRb) of 139 bp each separated by a small single copy (SSC) region of 54,323 bp (SSC) and a large single copy region of 66,735 bp (LSC). It contains 114 genes, 68 of which are protein coding genes, 35 tRNA and four rRNA genes, six open reading frames, and one pseudogene. Seventeen repeat units and 64 simple sequence repeats (SSR) have been detected in A. nephrolepis cp genome. Large IR sequences locate in 42-kb inversion points (1186 bp). The A. nephrolepis cp genome is identical to Abies koreana’s which is closely related to taxa. Pairwise comparison between two cp genomes revealed 140 polymorphic sites in each. Complete cp genome sequence of A. nephrolepis has a significant potential to provide information on the evolutionary pattern of Abietoideae and valuable data for development of DNA markers for easy identification and classification