Tuning the Level of Concurrency in Software Transactional Memory: An Overview of Recent Analytical, Machine Learning and Mixed Approaches

Synchronization transparency offered by Software Transactional Memory (STM) must not come at the expense of run-time efficiency, thus demanding from the STM-designer the inclusion of mechanisms properly oriented to performance and other quality indexes. Particularly, one core issue to cope with in STM is related to exploiting parallelism while also avoiding thrashing phenomena due to excessive transaction rollbacks, caused by excessively high levels of contention on logical resources, namely concurrently accessed data portions. A means to address run-time efficiency consists in dynamically determining the best-suited level of concurrency (number of threads) to be employed for running the application (or specific application phases) on top of the STM layer. For too low levels of concurrency, parallelism can be hampered. Conversely, over-dimensioning the concurrency level may give rise to the aforementioned thrashing phenomena caused by excessive data contention—an aspect which has reflections also on the side of reduced energy-efficiency. In this chapter we overview a set of recent techniques aimed at building “application-specific” performance models that can be exploited to dynamically tune the level of concurrency to the best-suited value. Although they share some base concepts while modeling the system performance vs the degree of concurrency, these techniques rely on disparate methods, such as machine learning or analytic methods (or combinations of the two), and achieve different tradeoffs in terms of the relation between the precision of the performance model and the latency for model instantiation. Implications of the different tradeoffs in real-life scenarios are also discussed

Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs

The long-term survival of biomaterial implants is often hampered by surgery-induced inflammation that can lead to graft failure. Considering that most corneas receiving grafts are either pathological or inflamed before implantation, the risk of rejection is heightened. Here, we show that bioengineered, fully synthetic, and robust corneal implants can be manufactured from a collagen analog (collagen-like peptide-polyethylene glycol hybrid, CLP-PEG) and inflammation-suppressing polymeric 2-methacryloyloxyethyl phosphorylcholine (MPC) when stabilized with the triazine-based crosslinker 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The resulting CLP-PEG-MPC implants led to reduced corneal swelling, haze, and neovascularization in comparison to CLP-PEG only implants when grafted into a mini-pig cornea alkali burn model of inflammation over 12 months. Implants incorporating MPC allowed for faster nerve regeneration and recovery of corneal sensation. CLP-PEG-MPC implants appear to be at a more advanced stage of regeneration than the CLP-PEG only implants, as evidenced by the presence of higher amounts of cornea-specific type V collagen, and a corresponding decrease in the presence of extracellular vesicles and exosomes in the corneal stroma, in keeping with the amounts present in healthy, unoperated corneas

Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants

Short collagen-like peptides (CLPs) are being proposed as alternatives to full-length collagen for use in tissue engineering, on their own as soft hydrogels, or conjugated to synthetic polymer for mechanical strength. However, despite intended clinical use, little is known about their safety and efficacy, mechanism of action or degree of similarity to the full-length counterparts they mimic. Here, we show the functional equivalence of a CLP conjugated to polyethylene glycol (CLP-PEG) to full-length recombinant human collagen in vitro and in promoting stable regeneration of corneal tissue and nerves in a preclinical mini-pig model. We also show that these peptide analogs exerted their pro-regeneration effects through stimulating extracellular vesicle production by host cells. Our results support future use of CLP-PEG implants for corneal regeneration, suggesting the feasibility of these or similar peptide analogs in clinical application in the eye and other tissues.Correction in: Acta Biomaterialia, Vol. 81, Pages 330-331.DOI: 10.1016/j.actbio.2018.10.009Correction in: Acta Biomaterialia, Vol.88, Pages 556-557.DOI: 10.1016/j.actbio.2019.01.046</p

New Technologies in Clinical Trials in Corneal Diseases and Limbal Stem Cell Deficiency: Review from the European Vision Institute Special Interest Focus Group Meeting

To discuss and evaluate new technologies for a better diagnosis of corneal diseases and limbal stem cell deficiency, the outcomes of a consensus process within the European Vision Institute (and of a workshop at the University of Cologne) are outlined. Various technologies are presented and analyzed for their potential clinical use also in defining new end points in clinical trials. The disease areas which are discussed comprise dry eye and ocular surface inflammation, imaging, and corneal neovascularization and corneal grafting/stem cell and cell transplantation. The unmet needs in the abovementioned disease areas are discussed, and realistically achievable new technologies for better diagnosis and use in clinical trials are outlined. To sum up, it can be said that there are several new technologies that can improve current diagnostics in the field of ophthalmology in the near future and will have impact on clinical trial end point design