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Hepatitis C virus (HCV) is the major cause of progressive liver disease such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Previously, we reported that a 29 nucleotide-long 2’-F pyrimidine modified RNA aptamer against the HCV nonstructural protein 5B efficiently inhibited HCV replication and suppressed HCV infectious virus particle formation in a cell culture system. In this study, we modified this aptamer through conjugation of cholesterol for in vivo availability. This cholesterol-conjugated aptamer (chol-aptamer) efficiently entered the cell and inhibited HCV RNA replication, without any alteration in gene expression profiling including innate immune response-related genes. Moreover, systemic administration of the chol-aptamer was well tolerated without any abnormalities in mice. To evaluate the pharmacokinetics of the chol-aptamer in vivo, dose proportionality, bioavailability, and pharmacokinetic parameters were evaluated by noncompartmental analyses in normal BALB/c mice. Population analysis was performed using nonlinear mixed effects modeling. Moreover, the pharmacokinetics of two different routes (intravenous, IV, versus intraperitoneal, IP) were compared. Cholesterol conjugation showed dose proportionality, extended the time that the aptamer was in the plasma, and enhanced aptamer exposure to the body. Noticeably, the IV route was more suitable than the IP route due to the chol-aptamer remaining in the plasma for a longer period of time.

Land use and land cover (LULC) form a baseline thematic map for monitoring, resource management, and planning activities and facilitate the development of strategies to balance conservation, conflicting uses, and development pressures. In this study, changes in LULC in North Sumatra, Indonesia, are simulated and predicted using an artificial-neural-network-based cellular automaton (ANN-CA) model. Five criteria (altitude, slope, aspect, distance from the road, and soil type) are used as exploratory data in the learning process of the ANN-CA model to determine their impacts on LULC changes between 1990 and 2000; among the criteria, altitude and distance from the road have strong impacts. Comparison between the predicted and the real LULC maps for 2010 illustrates high agreement, with a Kappa index of 0.83 and a percentage of correctness of 87.28%. Then, the ANN-CA model is applied to predict LULC changes in 2050 and 2070. The LULC predictions for 2050 and 2070 demonstrate high increases in plantation area of more than 4%. Meanwhile, forest and crop area are projected to decrease by approximately 1.2% and 1.6%, respectively, by 2050. By 2070, forest and crop areas will decrease by 1.2% and 1.7%, respectively, indicating human influences on LULC changes from forest and cropland to plantations. This study illustrates that the simulation of LULC changes using the ANN-CA model can produce reliable predictions for future LULC.

In this study, prediction of the future land use land cover (LULC) changes over Mumbai and its surrounding region, India, was conducted to have reference information in urban development. To obtain the historical dynamics of the LULC, a supervised classification algorithm was applied to the Landsat images of 1992, 2002, and 2011. Based on spatial drivers and LULC of 1992 and 2002, the multiple perceptron neural network (MLPNN)-based Markov chain model (MCM) was applied to simulate the LULC in 2011, which was further validated using kappa statistics. Thereafter, by using 2002 and 2011 LULC, MLPNN-MCM was applied to predict the LULC in 2050. This study predicted the prompt urban growth over the suburban regions of Mumbai, which shows, by 2050, the Urban class will occupy 46.87% (1328.77 km2) of the entire study area. As compared to the LULC in 2011, the Urban and Forest areas in 2050 will increase by 14.31% and 2.05%, respectively, while the area under the Agriculture/Sparsely Vegetated and Barren land will decline by 16.87%. The class of water and the coastal feature will experience minute fluctuations (<1%) in the future. The predicted LULC for 2050 can be used as a thematic map in various climatic, environmental, and urban planning models to achieve the aims of sustainable development over the region.

Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent studies have shown that ketones may modulate neuronal firing through interactions with ATP-sensitive potassium (KATP) channels. Here, we used a combination of electrophysiological, pharmacological, and biochemical assays to determine whether hippocampal synaptic protection by ketones is a consequence of KATP channel activation. Ketones dose-dependently reversed oxidative impairment of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity, and this action was mirrored by the KATP channel activator diazoxide. Inhibition of KATP channels reversed ketone-evoked hippocampal protection, and genetic ablation of the inwardly rectifying K+ channel subunit Kir6.2, a critical component of KATP channels, partially negated the synaptic protection afforded by ketones. This partial protection was completely reversed by co-application of the KATP blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of oxidative injury, ketones induce synaptic protection in part through activation of KATP channels.

In order to maintain stable blood pressure and heart rate during surgery, anesthesiologists need to administer the appropriate amount of fluid with appropriate fluid type to the patient, then quantifying how fluid is distributed and eliminated from the body is useful for establishing a fluid administration strategy. In this study we characterized the volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy. When propofol and remifentanil reached a pseudosteady state at the target concentration and blood pressure was stabilized following surgical stimulation, enrolled patients were administered 1000 mL of Ringer’s lactate solution for 20 min, followed by continuous infusion at a rate of 6 mL/kg/h until the time of the last blood collection for volume kinetic analysis. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. The change in hemoglobin-derived plasma dilution induced by the administration of Ringer’s lactate solution was evaluated by nonlinear mixed effects modeling. Three hundred and twenty-three plasma dilution data points from 27 patients were used to determine the pharmacokinetic characteristics of Ringer’s lactate solution. A two-volume model best described the pharmacokinetics of Ringer’s lactate solution. The mean arterial pressure (MAP) and body weight (WT) were significant covariates for the elimination clearance ( k r ) and central volume of distribution at baseline ( V c 0 ), respectively. The parameter estimates were as follows: k r (mL/min) = 124 + (MAP/70) 14.2 , V c 0 (mL) = 0.95 + 3440 × (WT/63), V t 0 (mL) = 2730, and k t (mL/min) = 181. A higher MAP was associated with a greater elimination clearance and, consequently, less water accumulation in the interstitium. As body weight increases, volume expansion in the blood vessels increases.

Changes in climate parameters such as air temperature, rainfall, and humidity may dramatically impact the occurrence of infectious diseases. Dengue fever is a prevalent disease that has been extensively reported in relatio to climate change, particularly in tropical countries such as Indonesia. In addition, the consequences of climate change may affect the physiological responses of our bodies, which could lead to a rise in hospital admissions even in tropical countries. Wet Bulb Globe Temperature (WBGT) is an index to estimate the effect of air temperature, humidity, and solar radiation on human bodies. First, this study aims to investigate the influence of climatic conditions, including air temperature (AT), relative humidity (RH), and rainfall (RF), on the occurrence of dengue fever in Jakarta, Bandung, and Malang city, through a cross-correlation analysis. Second, it also explains the relationships between WBGT and general emergency hospital admissions in Indonesia and Japan. The results showed that climate conditions such as rainfall and humidity had a strong correlation with the incidence of dengue in Indonesia, with a relatively short lag of around 2-5 months in the form of negative values, while positive values were observed with a lag of 9-10 months with some exceptions in Jakarta. Extreme WBGT changes do not affect general emergency hospital admissions in both Hiroshima and Indonesian cities, although the WBGT changes clearly affected the emergency hospital admissions caused by the heat stroke in Hiroshima.

The relationships between observed rainfall, El Niño/Southern Oscillation (ENSO) and sea surface temperature (SST) variations in the Pacific and Indian Oceans were analyzed using a 1° latitude–longitude grid over Indonesia. The Global Summary of the Day rainfall records provide 26 years of rainfall data (January 1985 to August 2010) for 23 stations throughout the Indonesian islands. The ENSO and SST variations were calculated using the Multivariate ENSO Index (MEI), the Pacific Decadal Oscillation (PDO), NINO1 + 2, NINO3, NINO3.4, NINO4, the Dipole Mode Index (DMI) for the Indian Ocean Dipole (IOD), and Indian Ocean Basin-wide (IOBW) index. The results show that the rainfall in the southern Sumatra and southern Java Islands, which face the Indian Ocean, was positively correlated with the negative IOD, whereas the rainfall in northwestern Sumatra was positively correlated with the positive IOD. In eastern Indonesia, the rainfall was positively correlated with La Niña. The PDO index was also strongly correlated with the rainfall in this region. In central Indonesia, seasonal variations due to monsoons are predominant, and the rainfall exhibited strong negative and positive correlations with the MEI and NINO.WEST, respectively, indicating that high rainfall occurred during strong La Niña episodes. The highly negative and positive correlations with the MEI and NINO.WEST, respectively, in central Indonesia led us to analyze the impacts of Indonesian seas on the rainfall in the region. Using four synoptic-scale scenarios, we investigated the relative residence time of Indonesian seawater along the pathways associated with the Pacific-Indian hydraulic head difference. The results show that when both the western Pacific and eastern Indian Oceans are warm (positive NINO.WEST and negative DMI), the rainfall intensity over central Indonesia is strongest. This increase is explained by the relationship between the residence time of Indonesian seawater and the exposure to surface evaporation: a longer exposure of Indonesian seas results in greater seawater warming and evaporation and more convection-generated cumulus clouds.

Flooding is one of the major destructive natural disasters in Davao Oriental, Philippines, and results primarily from a high incidence of typhoons and heavy rainfalls. The main objective of this study was to identify flood-prone risk areas by mapping them based on the integration of multiple indicators, including rainfall, slope, elevation, drainage density, soil type, distance to the main channel and population density. For this purpose, a GIS-based flood risk spatial assessment was conducted by using analytic hierarchy process (AHP), weights by rank (WR) and ratio weighting (RW) frameworks to determine the relative importance of each indicator against another in the province of Davao Oriental. The resulting flood-prone areas by the three methods are validated by comparing with the estimated flood map based on ground truthing points from a field survey. The comparison results show that AHP is the most appropriate method among them to assess flood hazard. The result of the AHP flood risk map shows that 95.99% (5451.27 km2) of Davao Oriental is under low and moderate flood risk. The high and very high flood risk area covers approximately 3.39% (192.52 km2) of the province, primarily in the coastal areas. Thirty-one out of the one hundred eighty-three (31/183) barangays (towns) are at a high to very high risk of flooding at current climate, calling for the immediate attention of decision-makers to develop mitigation strategies for the future occurrence of flooding in Davao Oriental.

The current study focuses on water scarcity, water shortages, and inequal water allocation for downstream water users in the Balkhab River basin (BRB) in northern Afghanistan. The Soil and Water Assessment Tool (SWAT) was utilized to determine the hydrological process in the watershed and assess the water resource capacity. The model was calibrated and validated to ensure proper model setup for the entire watershed. The analysis of the current water management and allocation scheme indicated inadequate water distributions for the downstream irrigation canals. The current water allocation approach was modified based on crop water requirements and the available agricultural lands. A new irrigation scheme was proposed and included in the SWAT model that does not decrease upstream water allocation. The annual streamflow in the Balkhab River can supply the extra allocated water downstream without influencing the upstream water. Notably, a dam was proposed in the middle stream to store water during the winter and early spring seasons, as well as floodwater. The model outcomes showed that the existing annual streamflow in the river can fully support the irrigation of currently available land and an extra 18,470.6 ha of agricultural lands in the BRB. The results of this study can contribute to scientific evidence-based policy and decision-making processes for sustainable agricultural water resource management and flood control in the study region.