Evolutionary responses to a changing climate: Implications for reindeer population viability

If we want to understand how climate change affects long‐lived organisms, we must know how individuals allocate resources between current reproduction and survival. This trade‐off is affected by expected environmental conditions, but the extent to which density independent (DI) and density dependent (DD) processes interact in shaping individual life histories is less clear. Female reindeer (or caribou: Rangifer tarandus) are a monotocous large herbivore with a circumpolar distribution. Individuals that experience unpredictable and potentially harsh winters typically adopt risk averse strategies where they allocate more resources to building own body reserves during summer and less to reproduction. Such a strategy implies that the females do not reproduce or that they produce fewer or smaller offspring. A risk averse strategy thus results in females with large autumn body reserves, which is known to increase their survival probabilities if the coming winter is harsh. In contrast, females experiencing predictable winters may adopt a more risk prone strategy in which they allocate more resources to reproduction as they do not need as many resources to buffer potentially adverse winter conditions. This study uses a seasonal state‐dependent model showing that DD and DI processes interact to affect the evolution of reproductive strategies and population dynamics for reindeer. The model was run across a wide range of different winter climatic scenarios: One set of simulations where the average and variability of the environment was manipulated and one set where the frequency of good and poor winters increased. Both reproductive allocation and population dynamics of reindeer were affected by a combination of DI and DD processes even though they were confounded (harsh climates resulted in lowered density). Individual strategies responded, in line with a risk sensitive reproductive allocation, to climatic conditions and in a similar fashion across the two climatic manipulations.     

Structure activity relationship and optimization of N-(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells

We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N-(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to standard treatments. This molecule also shows a good pharmacological profile and high in vivo potency towards mice xenografts, without signs of toxicity on the animals. In the present article, we disclose the structure-activity relationships of this lead compound, which have provided clear information about the replacement of the acetamide function and the substitution pattern of the benzenesulfonamide ring. An improved high-yielding synthetic procedure towards these compounds has also been developed. Our drug design resulted in potency enhancement of 1, our new optimized lead compound being 19. These findings are of great interest to further improve this scaffold for the development of future clinical candidates.     

Economic impact of combined torrefaction and pelletization processes on forestry biomass supply

The cost of supplying wood biomass from forestry operations in remote areas has been an obstacle to expansion of forest‐based bioenergy in much of the western United States. Economies of scale in the production of liquid fuels from lignocellulosic biomass feedstocks favor large centralized biorefineries. Increasing transportation efficiency through torrefaction and pelletization at distributed satellite facilities may serve as a means to expand the utilization of forestry residuals in biofuel production. To investigate this potential, a mixed‐integer linear program was developed to optimize the feedstock supply chain design with and without distributed pretreatment. The model uses techno‐economic assessment of scale‐dependent biomass pretreatment processes from existing literature and multimodal biomass transportation cost evaluations derived from a spatially explicit network analysis as input. In addition, the sensitivity of the optimal system configuration was determined for variations of key input parameters including the production scale of pretreatment facilities, road and rail transportation costs, and feedstock procurement costs. Torrefaction and densification were found to reduce transportation costs by $0.84 per GJ and overall delivered costs by $0.24 per GJ, representing 14.5% and 5.2% cost reductions compared to feedstock collection without pretreatment. Significant uncertainties remain in terms of the costs associated with deploying torrefaction equipment at the scales modeled, but the level of potential cost savings suggests further analysis and development of these alternatives.     

Simplex‐based optimization of numerical and categorical inputs in early bioprocess development: Case studies in HT chromatography

Bioprocess development studies often involve the investigation of numerical and categorical inputs via the adoption of Design of Experiments (DoE) techniques. An attractive alternative is the deployment of a grid compatible Simplex variant which has been shown to yield optima rapidly and consistently. In this work, the method is combined with dummy variables and it is deployed in three case studies wherein spaces are comprised of both categorical and numerical inputs, a situation intractable by traditional Simplex methods. The first study employs in silico data and lays out the dummy variable methodology. The latter two employ experimental data from chromatography based studies performed with the filter‐plate and miniature column High Throughput (HT) techniques. The solute of interest in the former case study was a monoclonal antibody whereas the latter dealt with the separation of a binary system of model proteins. The implemented approach prevented the stranding of the Simplex method at local optima, due to the arbitrary handling of the categorical inputs, and allowed for the concurrent optimization of numerical and categorical, multilevel and/or dichotomous, inputs. The deployment of the Simplex method, combined with dummy variables, was therefore entirely successful in identifying and characterizing global optima in all three case studies. The Simplex‐based method was further shown to be of equivalent efficiency to a DoE‐based approach, represented here by D‐Optimal designs. Such an approach failed, however, to both capture trends and identify optima, and led to poor operating conditions. It is suggested that the Simplex‐variant is suited to development activities involving numerical and categorical inputs in early bioprocess development.     

Animal component‐free Agrobacterium tumefaciens cultivation media for better GMP‐compliance increases biomass yield and pharmaceutical protein expression in Nicotiana benthamiana

Transient expression systems allow the rapid production of recombinant proteins in plants. Such systems can be scaled up to several hundred kilograms of biomass, making them suitable for the production of pharmaceutical proteins required at short notice, such as emergency vaccines. However, large‐scale transient expression requires the production of recombinant Agrobacterium tumefaciens strains with the capacity for efficient gene transfer to plant cells. The complex media often used for the cultivation of this species typically include animal‐derived ingredients that can contain human pathogens, thus conflicting with the requirements of good manufacturing practice (GMP). We replaced all the animal‐derived components in yeast extract broth (YEB) cultivation medium with soybean peptone, and then used a design‐of‐experiments approach to optimize the medium composition, increasing the biomass yield while maintaining high levels of transient expression in subsequent infiltration experiments. The resulting plant peptone Agrobacterium medium (PAM) achieved a two‐fold increase in OD₆₀₀ compared to YEB medium during a 4‐L batch fermentation lasting 18 h. Furthermore, the yields of the monoclonal antibody 2G12 and the fluorescent protein DsRed were maintained when the cells were cultivated in PAM rather than YEB. We have thus demonstrated a simple, efficient and scalable method for medium optimization that reduces process time and costs. The final optimized medium for the cultivation of A. tumefaciens completely lacks animal‐derived components, thus facilitating the GMP‐compliant large‐scale transient expression of recombinant proteins in plants.     

液态发酵豆粕制备纳豆激酶方法的优化

纳豆激酶是一种丝氨酸蛋白酶,具有很强的纤溶活性,由于具有安全性好、作用迅速持久、成本低等优点,适合用于开发新一代的溶栓剂或保健食品,具有广阔的市场前景。本研究探讨了以豆粕为原料液态发酵豆粕生产纳豆激酶的发酵方法。首先通过单因素实验发现影响产酶的主要因素有接菌量、发酵时间、培养基pH及豆粕含量,再由正交实验得到最优组合为接菌量1%,豆粕含量2%,pH为7.0,发酵时间48h,该条件下发酵酶活力最高达到4 429.6U/mL。本研究确定了以豆粕为原料制备纳豆激酶的最佳条件,为豆粕的合理使用和纳豆激酶的工业化生产提供了实验依据。     

Multi-body optimization with subject-specific knee models: performance at high knee flexion angles

When estimating knee kinematics from skin markers and stereophotogrammetry, multi-body optimization (MBO) has provided promising results for reducing soft tissue artefacts (STA), but can still be improved. The goal of this study was to assess the performance of MBO with subject-specific knee models at high knee flexion angles (up to 110°) against knee joint kinematics measured by magnetic resonance imaging. Eight subjects were recruited. MBO with subject-specific knee models was more effective in compensating STA compared to no kinematic and spherical constraints, in particular for joint displacements. Moreover, it seems to be more reliable over large ranges of knee flexion angle. The ranges of root mean square errors for knee rotations/displacements were 3.0°–9.2°/1.3–3.5 mm for subject-specific knee models, 6.8°–8.7°/6.0–12.4 mm without kinematic constraint and 7.1°–9.8°/4.9–12.5 mm for spherical constraints.     

Optimization of L-asparaginase production from novel Enterobacter sp., by submerged fermentation using response surface methodology

The culture conditions and nutritional rations influencing the production of extra cellular antileukemic enzyme by novel Enterobacter aerogenes KCTC2190/MTCC111 were optimized in shake-flask culture. Process variables like pH, temperature, incubation time, carbon and nitrogen sources, inducer concentration, and inoculum size were taken into account. In the present study, finest enzyme activity achieved by traditional one variable at a time method was 7.6 IU/mL which was a 2.6-fold increase compared to the initial value. Further, the L-asparaginase production was optimized using response surface methodology, and validated experimental result at optimized process variables gave 18.35 IU/mL of L-asparaginase activity, which is 2.4-times higher than the traditional optimization approach. The study explored the E. aerogenes MTCC111 as a potent and potential bacterial source for high yield of antileukemic drug.     

Location Optimization of Urban Mining Facilities with Maximal Covering Model in GIS: A Case of China

Urban mining offers an efficient supply of resources because of rich mines and low environmental impacts. Location selection and optimization for urban mining facilities is more complicated than for natural mines, given that it may vary according to the urban population, consumption habits, and economic development. China initiated the National Urban Mining Pilot Bases program in 2010 that targeted 50 national urban mining pilot bases, but unfortunately neglected the location planning issue. Twenty‐eight bases have already been selected, which are concentrated in the central and eastern areas of China. This article combines the use of analytic hierarchy process, maximal covering location model, and geographical information systems (GIS) software to optimize locations for China's urban mining pilot bases. Primary findings show that, theoretically, 40 urban mining pilot bases can sufficiently provide maximum gross domestic product (GDP) and population coverage service for China. Taking the current 28 bases as a precondition and 50 bases as the remaining policy target, our second optimization results in a list of 22 cities for the location selection of future urban mining pilot bases. In total, the optimized 22 cities, together with the selected 28 bases, can provide a maximum 97.5% of GDP and 95.1% of population coverage in China. This study illustrates the optimization process for urban mining recycling facilities in general and provides policy advice for China in a specific case.