Evolving Role for Pharmacotherapy in NAFLD/NASH

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent, dynamic disease that occurs across the age spectrum and can lead to cirrhosis and hepatocellular carcinoma. There are currently no US Food and Drug Administration (FDA) approved treatments for NAFLD; however, this is a field of active research. This review summarizes emerging pharmacotherapies for the treatment of adult and pediatric NAFLD. Investigated pharmacotherapies predominantly target bile acid signaling, insulin resistance, and lipid handling within the liver. Three drugs have gone on to phase III trials for which results are available. Of those, obeticholic acid is the single agent that demonstrates promise according to the interim analyses of the REGENERATE trial. Obeticholic acid showed reduction of fibrosis in adults with nonalcoholic steatohepatitis (NASH) taking 25 mg daily for 18 months (n = 931, reduction in fibrosis in 25% vs. 12% placebo, P \u3c 0.01). Ongoing phase III trials include REGENERATE and MAESTRO-NASH, which investigates thyroid hormone receptor-β agonist MGL-3196. Outcomes of promising phase II trials in adults with NASH are also available and those have investigated agents, including the fibroblast growth factor (FGF)19 analogue NGM282, the GLP1 agonist liraglutide, the FGF21 analogue Pegbelfermin, the sodium glucose co-transporter 2 inhibitor Empagliflozin, the ketohexokinase inhibitor PF-06835919, the acetyl-coenzyme A carboxylase inhibitor GS-0976, and the chemokine receptor antagonist Cenicriviroc. Completed and ongoing clinical trials emphasize the need for a more nuanced understanding of the phenotypes of subgroups within NAFLD that may respond to an individualized approach to pharmacotherapy

Three-Phase Linear Motor Heat Transfer Analysis Using the Finite-Element Method

As the need for speed and precision in modern manufacturing technologies increases, linear motors are attracting considerable research attention. Heat management and thermal deformation associated with linear motors comprise a major concern tied to the demand for machining accuracy. Here we describe a three-dimensional finite-element simulation analysis method that utilizes a three-phase linear synchronous motor for thermally characterizing a feed-driven system. We also present results from simulations and experiments aimed at verifying system thermal time constants and temperature distributions. These results demonstrate that the proposed analytical method is capable of making accurate and useful predictions of temperature and thermal behavior distributions for linear motors in terms of conventional heat generation in various transient and steady-state phases. It is our hope that these results will support future efforts to design modern feed-driven systems equipped with linear motors

CLIPCAM: A Simple Baseline For Zero-Shot Text-Guided Object And Action Localization

The key for the contemporary deep learning-based object and action localization algorithms to work is the large-scale annotated data. However, in real-world scenarios, since there are infinite amounts of unlabeled data beyond the categories of publicly available datasets, it is not only time- and manpower-consuming to annotate all the data but also requires a lot of computational resources to train the detectors. To address these issues, we show a simple and reliable baseline that can be easily obtained and work directly for the zero-shot text-guided object and action localization tasks without introducing additional training costs by using Grad-CAM, the widely used class visual saliency map generator, with the help of the recently released Contrastive Language-Image Pre-Training (CLIP) model by OpenAI, which is trained contrastively using the dataset of 400 million image-sentence pairs with rich cross-modal information between text semantics and image appearances. With extensive experiments on the Open Images and HICO-DET datasets, the results demonstrate the effectiveness of the proposed approach for the text-guided unseen object and action localization tasks for images

The international context for industrialisation in the coming decade

Focuses on the aspects of changing international climate including restricted market access, radical electronics-based technical change, structured adjustment programs and increased military expenditures in newly industrialized countries. Factors contributing to the expansion of global trade; Effects of protectionism on exports; Reason for the economic benefits of utilization of electronics-based automation technologies in innovating firms