FORMULATION AND DEVELOPMENT OF FIXED-DOSE COMBINATION OF BI-LAYER TABLETS OF EFAVIRENZ, LAMIVUDINE AND TENOFOVIR DISOPROXIL FUMARATE TABLETS 600 MG/300 MG/300 MG

Objective: This study is to formulate bi-layer tablet as a multidrug regimen against each reference listed drugs of Brand SUSTIVA® (efavirenz tablets 600 mg), EPIVER®(lamivudine tablets 300 mg), and VIREAD®(tenofovir disoproxil tablets 300 mg) to treat human immunodeficiency virus (HIV) infections. Which provides highly active antiretroviral therapy to provide effective treatment. Methods: Bilayer formulation was developed with each blend of layer-I (efavirenz) and layer-II (lamivudine and tenofovir disoproxil fumarate) through wet granulation process and roller compaction process, respectively. Further, both layers were compressed by using bi-layer compression followed by film coating. Layer-I and II formulations were developed by using various concentrations of diluents, surfactants, and disintegrants to improve the solubility of efavirenz and improve the flowability and uniformity of layer-II. Finally, the optimum formulation was developed to compare the in vitro dissolution with each branded formulation. Results: Drug-excipients interaction results revealed that the mixtures of three drug substances in 50 °C/75 % relative humidity (RH) resulted in an increase in tenofovir IMP-E and the highest unknown impurity was significantly increased and additionally decreased tenofovir assay in the presence of efavirenz. Sodium lauryl sulfate is very critical and it acts as a wetting agent and increases the solubility of efavirenz, and directly influences the dissolution of a drug product. Microcrystalline and croscarmellose sodium have a chance to affect the dissolution and friability of tenofovir. Powdered cellulose was acting as a diluent and flow property of the lamivudine part and it also affects the uniformity and dissolution. So, these ranges were optimized. X-ray diffraction (XRD) indicates there are no polymorphic changes for the optimized formulation and there is no interaction between the three active substances, and finally, in vitro dissolution results for the optimized formulation against the reference drugs. Conclusion: Optimum formulation yielded consistent drug release against each branded drug to treat human immunodeficiency virus (HIV1) infections. This formulation is robust and easily scale up for the next stage.

Multi-layer Hybrid Classification Model of COVID-19 Chest X-ray Images v1

The coronavirus disease of 2019(COVID-19) has been declared a pandemic and has raised worldwide concern. Lung inflammation and respiratory failure are commonly observed in moderate-to-severe cases. Radiography or chest X-ray imaging is compulsory for diagnosis, and interpretation is commonly performed by skilled medical specialists. In this study, we propose anew computer-aided diagnosis (CADx) tool for identifying chest X-ray images of COVID-19 infection using a multi-layer hybrid classification model (MLHC). The MLHC-COVID-19 consists of two layers, Layer I: Healthy and non-Healthy; Layer II: COVID-19 and non-COVID-19. The MLHC-COVID-19 was evaluated in real COVID-19 cases. The classification results showed promising performance comparable with other existing techniques considering the accuracy, sensitivity, and specificity of 96.20%, 96.20%, and 0.971%, respectively. This demonstrates the effectiveness of the MLHC-COVID-19 in classifying chest X-ray images, enhancing the accuracy of chest X-ray image interpretation with a reduction in the interpretation time. Furthermore, a detailed comparison of the MLHC-COVID-19 with other techniques has been presented.

Successful Reservoir Fluid Characterization and Testing While Overcoming the Challenges of Falling Oil Price and a Pandemic: A First for an Integrated Brown Field Alliance Project in Sarawak, Malaysia

A brown field, offshore Sarawak, Malaysia, with multiple sub-layered laminated sands of varied pressure regimes and mobility ranges, was challenged by depletion, low mobility and uncertainty in the current fluid types and contacts. Optimal dynamic fluid characterization and testing techniques comprising both Wireline and Logging While Drilling (LWD) were applied in nine development wells to acquire reliable formation pressure data and collect representative fluid samples including fluid scanning. Some of the latest technologies were deployed during the dual crises of falling oil price and the Covid-19 pandemic. The S-profile wells were drilled using oil-base mud (OBM) with an average deviation of 60 degrees. Formation Pressure While Drilling (FPWD), Fluid Sampling While Drilling (FSWD) and wireline formation testing, and sampling were all utilized allowing appropriate assessment of zones of interest. Various probe types such as Conventional Circular, Reinforced Circular, Elongated, Extra-Elongated and Extended Range Focused were used successfully, ensuring that the right technology was deployed for the right job. Formation pressure and fluid samples were secured in a timely manner to minimize reservoir damage and optimize rig time without jeopardizing the data quality. As a classified crisis due to the pandemic, rather than delaying the operations, a Remote Operations Monitoring and Control Center was set-up in town to aid the limited crew at rig site. A high success rate was achieved in acquiring the latest formation pressure regimes, fluid gradients, scanning and sampling, allowing the best completion strategy to be implemented. With the selection of the appropriate probe type at individual sands, 336 pressure tests were conducted, 44 fluid gradients were established, 27 fluid identification (fluid-id / scanning) pump-outs were performed, and 20 representative formation fluid samples (oil, gas, water) were collected. Amongst the Layer-III, Layer-II and Layer-I sands, Layer-I was tight, with mobility < 1.0 mD/cP. Wireline focused probe sampling provided clean oil samples with 1.4 to-3.7 wt. % OBM filtrate contamination. The water samples collected from Layer-II during FSWD proved to be formation water and not injection water. The wells were thus completed as oil producers. Reliable fluid typing and PVT quality sampling at discrete depths saved rig time and eliminated the requirement of additional runs or services including Drill Stem Testing (DST). This case study has many firsts. It is the first time where latest fluid characterization and testing technologies in both Wireline and LWD were deployed for an alliance project in Malaysia and that too during dual crises of falling oil price and the pandemic aftermath. Overcoming various challenges including limited rig site manpower, there was no delay in completing the highly deviated wells with tight formations in a single drilling campaign and provided rig time savings. For the purpose of this case study, two wells have been discussed. First well used the wireline focused sampling technology and the second used the FSWD technology.

The Effect of Deep Learning-Based QSM Magnetic Resonance Imaging on the Subthalamic Nucleus

In order to study the influence of quantitative magnetic susceptibility mapping (QSM) on them. A 2.5D Attention U-Net Network based on multiple input and multiple output, a method for segmenting RN, SN, and STN regions in high-resolution QSM images is proposed, and deep learning realizes accurate segmentation of deep nuclei in brain QSM images. Experimental results show data first cuts each layer of 0 100 case data, based on the image center, from 384 × 288 to the size of 128 × 128. Image combination: each layer of the image in the layer direction combines with two adjacent images into a 2.5D image, i.e., (It − m It; It + i), where It represents the layer i image. At this time, the size of the image changes from 128 × 128 to 128 × 128 × 3, in which 3 represents three consecutive layers of images. The SNR of SWP I to STN is twice that of SWI. The small deep gray matter nuclei (RN, SN, and STN) in QSM images of the brain and the pancreas with irregular shape and large individual differences in abdominal CT images can be automatically segmented.

Simulation analysis to optimize the performance of homojunction p-i-n In0.7Ga0.3N solar cell

Simulation analysis has been carried out to determine the perfect structural parameters of homojunction p-i-n In0.7Ga0.3N solar cell to obtain maximum overall efficiency. It has been demonstrated that n-layer of 16-nm, intrinsic layer (i-layer) of 0.5-μm and p-layer of 3-μm thickness with specific doping concentrations of 1·1020 cm–3 for n-layer and 1·1018 cm–3 for p-layer allow us to achieve the maximum efficiency 29.21%. The solar cell structure provides an open circuit voltage of 1.0 V, short circuit current density of 33.15 mA/cm2 and the percentage of fill factor value of 88.03%. However, the efficiency drops drastically, if the dislocation density in i-layer is higher than 1·1014 cm–3, and unintentional doping concentration within i-layer is beyond 1.5·1016 cm–3 of the structure.

THE TEMPO OF CULTURAL CHANGE IN THE KOSTENKI UPPER PALEOLITHIC: FURTHER INSIGHTS

ABSTRACT The Kostenki-Borshchevo site complex (Voronezh region, Russia) serves as the foundation of Eastern Europe’s Upper Paleolithic chronocultural framework. Here we present new radiocarbon dates for three Kostenki sites. Dates of ∼27.5–27 ka BP for Kostenki 15 suggest that its archaeological layer accumulated over a short period. These results help to confirm that the site is unrelated to Aurignacian assemblages. New dates for the Kostenki-Avdeevo Culture (KAC) Layer I of Kostenki 1 address the longstanding question of its chronology. Our results of ∼23.5–23 ka BP from different areas of the site are consistent with the layer’s accumulation over a short period. These results accord with recently obtained dates for Kostenki’s other KAC sites. Our younger results of ∼22.5–21 ka BP for different material from Layer III of Kostenki 21 are similarly consistent with a short chronological window for Kostenki’s KAC sites. Overall, this and other recent publications support the view that many Kostenki assemblages are chronologically distinct. This provides an important insight into the tempo of Upper Paleolithic cultural change.

Abnormal Rat Cortical Development Induced by Ventricular Injection of rHMGB1 Mimics the Pathophysiology of Human Cortical Dysplasia

Cortical dysplasia (CD) is a common cause of drug-resistant epilepsy. Increasing studies have implicated innate immunity in CD with epilepsy. However, it is unclear whether innate immune factors induce epileptogenic CD. Here, we injected recombinant human high mobility group box 1 (rHMGB1) into embryonic rat ventricles to determine whether rHMGB1 can induce epileptogenic CD with pathophysiological characteristics similar to those of human CD. Compared with controls and 0.1 μg rHMGB1-treated rats, the cortical organization was severely disrupted in the 0.2 μg rHMGB1-treated rats, and microgyria and heterotopia also emerged; additionally, disoriented and deformed neurons were observed in the cortical lesions and heterotopias. Subcortical heterotopia appeared in the white matter and the gray–white junction of the 0.2 μg rHMGB1-treated rats. Moreover, there was decreased number of neurons in layer V–VI and an increased number of astrocytes in layer I and V of the cortical lesions. And the HMGB1 antagonist dexmedetomidine alleviated the changes induced by rHMGB1. Further, we found that TLR4 and NF-κB were increased after rHMGB1 administration. In addition, the excitatory receptors, N-methyl-D-aspartate receptor 1 (NR1), 2A (NR2A), and 2B (NR2B) immunoreactivity were increased, and immunoreactivity of excitatory amino acid transporter 1 (EAAT1) and 2 (EAAT2) were reduced in 0.2 μg rHMGB1-treated rats compared with controls. While there were no differences in the glutamic acid decarboxylase 65/67 (GAD65/67) immunoreactivity between the two groups. These results indicate that the excitation of cortical lesions was significantly increased. Furthermore, electroencephalogram (EEG) showed a shorter latency of seizure onset and a higher incidence of status epilepticus in the 0.2 μg rHMGB1-treated rats; the frequency and amplitude of EEG were higher in the treated rats than controls. Intriguingly, spontaneous electrographic seizure discharges were detected in the 0.2 μg rHMGB1-treated rats after 5 months of age, and spike-wave discharges of approximately 8 Hz were the most significantly increased synchronous propagated waves throughout the general brain cortex. Taken together, these findings indicate that rHMGB1 exposure during pregnancy could contribute to the development of epileptogenic CD, which mimicked some pathophysiological characteristics of human CD.

Remyelination restores myelin content on distinct neuronal subtypes in the cerebral cortex

ABSTRACTAxons in the cerebral cortex exhibit diverse patterns of myelination, with some axons devoid of myelin, some exhibiting discontinuous patches of myelin, and others continuous myelin that is interrupted only by nodes of Ranvier. Oligodendrocytes establish this pattern by sorting through a high density of potential targets to select a small cohort of axons for myelination; however, the myelination patterns established on distinct excitatory and inhibitory neurons within the cortex remain to be fully defined and little is known about the extent to which these patterns are restored after oligodendrocyte regeneration. Here we show that axons in layer I of the somatosensory cortex, a key region for integration of input from local and distant sources, exhibit an extraordinarily diverse range of myelination patterns, even among distinct neuronal subtypes. Although larger axons were more often selected for myelination, neuronal identity profoundly influenced the probability of myelination. The relative differences in myelination among neuron subtypes were preserved between cortical areas with widely varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis, rather than selective reduction of myelin on distinct neuron subtypes. By following the loss and regeneration of myelin sheaths along defined neurons in vivo we show that even though the distribution of myelin on individual PV and VM neuron axons was altered following remyelination, the overall myelin content on these neurons was restored. The findings suggest that local changes in myelin can be tolerated, allowing opportunistic selection of available targets by newly formed oligodendrocytes to restore relative differences in myelin content between functionally distinct neurons.