Generative adversarial networks (GANs) have been extensively studied in the past few years. Arguably their most significant impact has been in the area of computer vision where great advances have ...been made in challenges such as plausible image generation, image-to-image translation, facial attribute manipulation, and similar domains. Despite the significant successes achieved to date, applying GANs to real-world problems still poses significant challenges, three of which we focus on here. These are as follows: (1) the generation of high quality images, (2) diversity of image generation, and (3) stabilizing training. Focusing on the degree to which popular GAN technologies have made progress against these challenges, we provide a detailed review of the state-of-the-art in GAN-related research in the published scientific literature. We further structure this review through a convenient taxonomy we have adopted based on variations in GAN architectures and loss functions. While several reviews for GANs have been presented to date, none have considered the status of this field based on their progress toward addressing practical challenges relevant to computer vision. Accordingly, we review and critically discuss the most popular architecture-variant, and loss-variant GANs, for tackling these challenges. Our objective is to provide an overview as well as a critical analysis of the status of GAN research in terms of relevant progress toward critical computer vision application requirements. As we do this we also discuss the most compelling applications in computer vision in which GANs have demonstrated considerable success along with some suggestions for future research directions. Codes related to the GAN-variants studied in this work is summarized on https://github.com/sheqi/GAN_Review.
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IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
This review discusses the complex nature of the primary nonstarch polysaccharide (NSP) in corn with respect to the merit of debranching enzymes. Celluloses, hemicelluloses, and pectins comprise the 3 ...major categories of NSP that make up nearly 90% of plant cell walls. Across cereals, the hemicellulose arabinoxylan exists as the primary NSP, followed by cellulose, glucans, and others. Differences in arabinoxylan structure among cereals and cereal fractions are facilitated by cereal type, degree and pattern of substitution along the xylan backbone, phenol content, and cross-linkages. In particular, arabinoxylan (also called glucuronoarabinoxylan) in corn is heavily fortified with substituents, being more populated than in wheat and other cereal grains. Feed-grade xylanases – almost solely of the glycoside hydrolase (GH) 10 and GH 11 families – require at least 2 or 3 contiguous xylose units to be free of attachments to effectively attack the xylan chain. This canopy of attachments, along with a high phenol content and the insoluble nature of corn glucuronoarabinoxylan, confers a significant resistance to xylanase attack. Both in vitro and in vivo studies demonstrate that debranching enzymes appreciably increase xylanase access and fiber degradability by removing these attachments and breaking phenolic linkages. The enzymatic degradation of the highly branched arabinoxylan can facilitate disassembly of other fibers by increasing exposure to pertinent carbohydrases. For cereals, the arabinofuranosidases, α-glucuronidases, and esterases are some of the more germane debranching enzymes. Enzyme composites beyond the simple core mixes of xylanases, cellulases, and glucanases can exploit synergistic benefits generated by this class of enzymes. A broad scope of enzymatic activity in customized mixes can more effectively target the resilient NSP construct of cereal grains in commercial poultry diets, particularly those in corn-based feeds.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Intravenous Ig (IVIg), plasma exchange, and immunoadsorption are frequently used in the management of severe autoimmune diseases mediated by pathogenic IgG autoantibodies. These approaches modulating ...IgG levels can, however, be associated with some severe adverse reactions and a substantial burden to patients. Targeting the neonatal Fc receptor (FcRn) presents an innovative and potentially more effective, safer, and more convenient alternative for clearing pathogenic IgGs.
A randomized, double-blind, placebo-controlled first-in-human study was conducted in 62 healthy volunteers to explore single and multiple ascending intravenous doses of the FcRn antagonist efgartigimod. The study objectives were to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. The findings of this study were compared with the pharmacodynamics profile elicited by efgartigimod in cynomolgus monkeys.
Efgartigimod treatment resulted in a rapid and specific clearance of serum IgG levels in both cynomolgus monkeys and healthy volunteers. In humans, single administration of efgartigimod reduced IgG levels up to 50%, while multiple dosing further lowered IgGs on average by 75% of baseline levels. Approximately 8 weeks following the last administration, IgG levels returned to baseline. Efgartigimod did not alter the homeostasis of albumin or Igs other than IgG, and no serious adverse events related to efgartigimod infusion were observed.
Antagonizing FcRn using efgartigimod is safe and results in a specific, profound, and sustained reduction of serum IgG levels. These results warrant further evaluation of this therapeutic approach in IgG-driven autoimmune diseases.
Clinicaltrials.gov NCT03457649.
argenx BVBA.
The MHC class I-related receptor FcRn serves multiple roles ranging from the regulation of levels of IgG isotype antibodies and albumin throughout the body to the delivery of antigen into antigen ...loading compartments in specialized antigen-presenting cells. In parallel with studies directed towards understanding FcRn at the molecular and cellular levels, there has been an enormous expansion in the development of engineering strategies involving FcRn to modulate the dynamic behavior of antibodies, antigens, and albumin. In this review article, we focus on a discussion of FcRn-targeted approaches that have resulted in the production of novel antibody-based platforms with considerable potential for use in the clinic.
Improved knowledge of FcRn at both molecular and cellular levels can be used towards better designing of novel classes of therapeutic antibodies.
Engineering antibodies to modulate their interaction with FcRn has resulted in several strategies to alter their dynamic behavior.
Half-life extended therapeutic antibodies with substantial increases in persistence in the body have been developed and are currently in clinical trials.
Antibodies that bind to their target antigen in a pH-dependent way (‘acid-switched’ antibodies) have been shown to be superior agents for the clearance of inflammatory cytokines, regulators of cholesterol levels, etc., from the body.
Engineered inhibitors that block the binding of antibodies to FcRn could provide a new generation of therapeutics to reduce the levels of pathogenic antibodies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary
Objective
The objective of this study is to compare the effects of high‐intensity interval training (HIIT) and moderate‐intensity continuous training (MICT) for improvements in body ...composition in overweight and obese adults.
Methods
Trials comparing HIIT and MICT in overweight or obese participants aged 18–45 years were included. Direct measures (e.g. whole‐body fat mass) and indirect measures (e.g. waist circumference) were examined.
Results
From 1,334 articles initially screened, 13 were included. Studies averaged 10 weeks × 3 sessions per week training. Both HIIT and MICT elicited significant (p < 0.05) reductions in whole‐body fat mass and waist circumference. There were no significant differences between HIIT and MICT for any body composition measure, but HIIT required ~40% less training time commitment. Running training displayed large effects on whole‐body fat mass for both HIIT and MICT (standardized mean difference −0.82 and −0.85, respectively), but cycling training did not induce fat loss.
Conclusions
Short‐term moderate‐intensity to high‐intensity exercise training can induce modest body composition improvements in overweight and obese individuals without accompanying body‐weight changes. HIIT and MICT show similar effectiveness across all body composition measures suggesting that HIIT may be a time‐efficient component of weight management programs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Neurons decentralize protein synthesis from the cell body to support the active metabolism of remote dendritic and axonal compartments. The neuronal RNA transport apparatus, composed of cis-acting ...RNA regulatory elements, neuronal transport granule proteins, and motor adaptor complexes, drives the long-distance RNA trafficking required for local protein synthesis. Over the past decade, advances in human genetics, subcellular biochemistry, and high-resolution imaging have implicated each member of the apparatus in several neurodegenerative diseases, establishing failed RNA transport and associated processes as a unifying pathomechanism. In this review, we deconstruct the RNA transport apparatus, exploring each constituent's role in RNA localization and illuminating their unique contributions to neurodegeneration.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Probiotics are living microorganisms that are generally thought of as being beneficial to the recipient. They have been shown to be effective in people with acute infectious diarrhoea, and ...cost-effective in antibiotic-associated diarrhoea. Probiotics may have a role in people with cancer, as various cancer treatments often lead to diarrhoea. However, as people with cancer are often immunocompromised, it is important to assess for adverse events (AEs) such as infection, which could potentially be a consequence of deliberate ingestion of living microorganisms.
A systematic review was carried out to collect, analyse and synthesise all available data on the efficacy and safety of probiotics in people with cancer (PROSPERO registration: CRD42012003454). Randomised, controlled trials, identified through screening multiple databases and grey literature, were included for analysing efficacy, while all studies were included for the analysis of safety of probiotics. Primary outcomes were the reduction in duration, severity and incidence of antibiotic-associated diarrhoea and chemotherapy-associated diarrhoea, and AEs, especially probiotic-associated infection. Where possible, data were combined for meta-analysis by a random-effects model, assessing causes of heterogeneity, including differences in strains, dosage and patient characteristics.
Eleven studies (N = 1557 participants) were included for assessing efficacy. Results show that probiotics may reduce the severity and frequency of diarrhoea in patients with cancer and may reduce the requirement for anti-diarrhoeal medication, but more studies are needed to assess the true effect. For example comparing probiotic use to control 25 groups on effect on Common Toxicity Criteria ≥2 grade diarrhoea, odds ratio (OR) = 0.32 95% confidence interval (CI) of 0.13–0.79; P = 0.01. Seventeen studies (N = 1530) were included in the safety analysis. Five case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures.
Probiotics may be a rare cause of sepsis. Further evidence needs to be collated to determine whether probiotics provide a significant overall benefit for people with cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We improve the potency of antibody-drug conjugates (ADCs) containing the human epidermal growth factor receptor 2 (HER2)-specific antibody pertuzumab by substantially reducing their affinity for HER2 ...at acidic endosomal pH relative to near neutral pH. These engineered pertuzumab variants show increased lysosomal delivery and cytotoxicity towards tumor cells expressing intermediate HER2 levels. In HER2
xenograft tumor models in mice, the variants show higher therapeutic efficacy than the parent ADC and a clinically approved HER2-specific ADC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Numerous studies have reported significant associations between ABO blood group and risk of cardiovascular disease. These studies have consistently demonstrated that thrombotic risk is significantly ...reduced in individuals in blood group O. Nevertheless, the biological mechanisms through which ABO influences hemostasis have remained poorly understood. Exciting recent data have provided novel insights into how these ABO effects are modulated and have highlighted that ABO group significantly influences platelet plug formation at sites of vascular injury (primary hemostasis). In particular, ABO affects multiple aspects of von Willebrand factor (VWF) biology. In keeping with their reduced thrombotic risk, plasma VWF levels are ∼25% lower in healthy group O compared with healthy group non-O individuals. In addition, blood group O VWF demonstrates enhanced susceptibility to ADAMTS13 proteolysis. Finally, preliminary findings suggest that the interaction of group O VWF with platelets may also be reduced. Although the molecular mechanisms underlying these ABO effects on VWF have not been fully elucidated, it seems likely that they are mediated in large part by the ABO(H) carbohydrate structures that are carried on both the N- and O-linked glycans of VWF. Interestingly, ABO(H) determinants are also expressed on several different platelet surface glycoprotein receptors. Recent studies support the hypothesis that ABO group not only exerts major quantitative and qualitative effects on VWF, but also affect specific aspects of platelet function. Given the severe morbidity and the mortality associated with thrombotic disorders, defining the mechanisms underlying these ABO effects is not only of scientific interest, but also of direct clinical importance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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