Task allocation in a multi-server system

We consider a slotted queueing system with $C$ servers (processors) that can handle tasks (jobs). Tasks arrive in batches of random size at the start of every slot. Any task can be executed by any server in one slot with success probability $alpha$. If a task execution fails, then the task must be handled in some later time slot until it has been completed successfully. Tasks may be processed by several servers simultaneously. In that case, the task is completed successfully if the task execution is successful on at least one of the servers. We determine the distribution of the number of tasks in the system for a broad class of task allocation strategies. Subsequently, we examine the impact of various allocation strategies on the mean number of tasks in the system and the mean response time of tasks. It is proven that both these performance measures are minimized by the strategy which always distributes the tasks over the servers as evenly as possible. Some numerical experiments are performed to illustrate the performance characteristics of the various strategies for a wide range of scenarios

Convergent cascade catalyzed by monooxygenase - alcohol dehydrogenase fusion applied in organic media

With the aim of applying redox-neutral cascade reactions in organic media, fusions of a type II flavin-containing monooxy-genase (FMO-E) and horse liver alcohol dehydrogenase (HLADH) were designed. The enzyme orientation and expression vector were found to influence the overall fusion enzyme activity. The resulting bi-functional enzyme retained the catalytic properties of both individual enzymes. The lyophilized cell free extract containing the bifunctional enzyme was applied for the convergent cascade reaction consisting of cyclobutanone and 1,4-butanediol in different micro-aqueous media with only 5% (v/v) aqueous buffer without any addition of external cofactor. Methyl tert-butyl ether and cyclopentyl methyl ether were found to be the best organic media for the synthesis of γ-butyrolactone resulting in ~27% analytical yield

Baeyer-Villiger Monooxygenases:Tunable Oxidative Biocatalysts

Pollution, accidents, and misinformation have earned the pharmaceutical and chemical industry a poor public reputation, despite their undisputable importance to society. Biotechnological advances hold the promise to enable a future of drastically reduced environmental impact and rigorously more efficient production routes at the same time. This is exemplified in the Baeyer-Villiger reaction, which offers a simple synthetic route to oxidize ketones to esters, but application is hampered by the requirement of hazardous and dangerous reagents. As an attractive alternative, flavin-containing Baeyer-Villiger monooxygenases (BVMOs) have been investigated for their potential as biocatalysts for a long time, and many variants have been characterized. After a general look at the state of biotechnology, we here summarize the literature on biochemical characterizations, mechanistic and structural investigations, as well as enzyme engineering efforts in BVMOs. With a focus on recent developments, we critically outline the advances toward tuning these enzymes suitable for industrial applications

Approaching boiling point stability of an alcohol dehydrogenase through computationally-guided enzyme engineering

Enzyme instability is an important limitation for the investigation and application of enzymes. Therefore, methods to rapidly and effectively improve enzyme stability are highly appealing. In this study we applied a computational method (FRESCO) to guide the engineering of an alcohol dehydrogenase. Of the 177 selected mutations, 25 mutations brought about a significant increase in apparent melting temperature (ΔTm ≥ +3 °C). By combining mutations, a 10-fold mutant was generated with a Tm of 94 °C (+51 °C relative to wildtype), almost reaching water's boiling point, and the highest increase with FRESCO to date. The 10-fold mutant's structure was elucidated, which enabled the identification of an activity-impairing mutation. After reverting this mutation, the enzyme showed no loss in activity compared to wildtype, while displaying a Tm of 88 °C (+45 °C relative to wildtype). This work demonstrates the value of enzyme stabilization through computational library design

Coupled reactions by coupled enzymes:alcohol to lactone cascade with alcohol dehydrogenase-cyclohexanone monooxygenase fusions

The combination of redox enzymes for redox-neutral cascade reactions has received increasing appreciation. An example is the combination of an alcohol dehydrogenase (ADH) with a cyclohexanone monooxygenase (CHMO). The ADH can use NADP(+) to oxidize cyclohexanol to form cyclohexanone and NADPH. Both products are then used by CHMO to produce ε-caprolactone. In this study, these two redox-complementary enzymes were fused, to create a self-sufficient bifunctional enzyme that can convert alcohols to esters or lactones. Three different ADH genes were fused to a gene coding for a thermostable CHMO, in both orientations (ADH-CHMO and CHMO-ADH). All six fusion enzymes could be produced and purified. For two of the three ADHs, we found a clear difference between the two orientations: one that showed the expected ADH activity, and one that showed low to no activity. The ADH activity of each fusion enzyme correlated with its oligomerization state. All fusions retained CHMO activity, and stability was hardly affected. The TbADH-TmCHMO fusion was selected to perform a cascade reaction, producing ε-caprolactone from cyclohexanol. By circumventing substrate and product inhibition, a > 99% conversion of 200 mM cyclohexanol could be achieved in 24 h, with > 13,000 turnovers per fusion enzyme molecule

A strategy for the robust forecasting of gas turbine health subjected to fouling

Fouling represents a major problem for Gas Turbines (GTs) in both heavy-duty and aeropropulsion applications. Solid particles entering the engine can stick to the internal surfaces and form deposits. Components' lifetime and performance can dramatically vary as a consequence of this phenomenon. These effects impact the whole engine in terms of residual life, operating stability, and maintenance costs. In the High-Pressure Turbine (HPT), in particular, the high temperatures soft the particles and promote their adhesion, especially in the short term. Unfortunately, predicting the GT response to this detrimental issue is still an open problem for scientists. Furthermore, the stochastic variations of the components operating conditions increase the uncertainty of the forecasting results. In this work, a strategy to predict the effects of turbine fouling on the whole engine is proposed. A stationary Gas Path Analysis (GPA) has been performed for this scope to predict the GT health parameters. Their alteration as a consequence of fouling has been evaluated by scaling the turbine map. The scaling factor has been found by performing Computational Fluid Dynamic (CFD) simulations of a HPT nozzle with particle injection. Being its operating conditions strongly uncertain, a stochastic analysis has been conducted. The uncertainty sources considered are the circumferential hot core location and the turbulence level at the inlet. The study enables to build of confidence intervals on the GT health parameters predictions and represents a step forward towards a robust forecasting tool

Image-guided multisession radiosurgery of skull base meningiomas

Background: The efficacy of single-session stereotactic radiosurgery (sSRS) for the treatment of intracranial meningioma is widely recognized. However, sSRS is not always feasible in cases of large tumors and those lying close to critically radiation-sensitive structures. When surgery is not recommended, multi-session stereotactic radiosurgery (mSRS) can be applied. Even so, the efficacy and best treatment schedule of mSRS are not yet established. The aim of this study is to validate the role of mSRS in the treatment of skull base meningiomas. Methods: A retrospective analysis of patients with skull base meningiomas treated with mSRS (two to five fractions) at the University of Messina, Italy, from 2008 to 2018, was conducted. Results: 156 patients met the inclusion criteria. The median follow-up period was 36.2 \ub1 29.3 months. Progression-free survival at 2-, 5-, and 10-years was 95%, 90%, and 80.8%, respectively. There were no new visual or motor deficits, nor cranial nerves impairments, excluding trigeminal neuralgia, which was reported by 5.7% of patients. One patient reported carotid occlusion and one developed brain edema. Conclusion: Multisession radiosurgery is an effective approach for skull base meningiomas. The long-term control is comparable to that obtained with conventionally-fractionated radiotherapy, while the toxicity rate is very limited

Understanding and Estimating Effective Population Size for Practical Application in Marine Species Management

Effective population size (Ne) determines the strength of genetic drift in a population and has long been recognized as an important parameter for evaluating conservation status and threats to genetic health of populations. Specifically, an estimate of Ne is crucial to management because it integrates genetic effects with the life history of the species, allowing for predictions of a population’s current and future viability. Nevertheless, compared with ecological and demographic parameters, Ne has had limited influence on species management, beyond its application in very small populations. Recent developments have substantially improved Ne estimation; however, some obstacles remain for the practical application of Ne estimates. For example, the need to define the spatial and temporal scale of measurement makes the concept complex and sometimes difficult to interpret. We reviewed approaches to estimation of Ne over both long-term and contemporary time frames, clarifying their interpretations with respect to local populations and the global metapopulation. We describe multiple experimental factors affecting robustness of contemporary Ne estimates and suggest that different sampling designs can be combined to compare largely independent measures of Ne for improved confidence in the result. Large populations with moderate gene flow pose the greatest challenges to robust estimation of contemporary Ne and require careful consideration of sampling and analysis to minimize estimator bias. We emphasize the practical utility of estimating Ne by highlighting its relevance to the adaptive potential of a population and describing applications in management of marine populations, where the focus is not always on critically endangered populations. Two cases discussed include the mechanisms generating Ne estimates many orders of magnitude lower than census N in harvested marine fishes and the predicted reduction in Ne from hatchery-based population supplementation

Understanding and Estimating Effective Population Size for Practical Application in Marine Species Management

Effective population size (Ne) determines the strength of genetic drift in a population and has long been recognized as an important parameter for evaluating conservation status and threats to genetic health of populations. Specifically, an estimate of Ne is crucial to management because it integrates genetic effects with the life history of the species, allowing for predictions of a population’s current and future viability. Nevertheless, compared with ecological and demographic parameters, Ne has had limited influence on species management, beyond its application in very small populations. Recent developments have substantially improved Ne estimation; however, some obstacles remain for the practical application of Ne estimates. For example, the need to define the spatial and temporal scale of measurement makes the concept complex and sometimes difficult to interpret. We reviewed approaches to estimation of Ne over both long-term and contemporary time frames, clarifying their interpretations with respect to local populations and the global metapopulation. We describe multiple experimental factors affecting robustness of contemporary Ne estimates and suggest that different sampling designs can be combined to compare largely independent measures of Ne for improved confidence in the result. Large populations with moderate gene flow pose the greatest challenges to robust estimation of contemporary Ne and require careful consideration of sampling and analysis to minimize estimator bias. We emphasize the practical utility of estimating Ne by highlighting its relevance to the adaptive potential of a population and describing applications in management of marine populations, where the focus is not always on critically endangered populations. Two cases discussed include the mechanisms generating Ne estimates many orders of magnitude lower than census N in harvested marine fishes and the predicted reduction in Ne from hatchery-based population supplementation