Significant amounts of soluble product aggregates were observed in the low-pH viral inactivation (VI) opertion during an initial scale-up run for an IgG4 monoclonal antibody (mAb IgG4-N1). Being earlier in development, a scale-down model did not exist, nor was it practical to use costly Protein A eluate (PAE) for testing the VI process at scale, thus, a computational fluid dynamics (CFD)-based high molecular weight (HMW) prediction model was developed for troubleshooting and risk mitigation. It was previously reported that the IgG4-N1 molecules upon exposure to low pH tend to change into transient and partially unfolded monomers during VI acidification (i.e., VIA) and form aggregates after neutralization (i.e., VIN) (Jin et al. 2019). Therefore, the CFD model reported here focuses on the VIA step. The model mimics the continuous addition of acid to PAE and tracks acid distribution during VIA. Based on the simulated low-pH zone (≤ pH 3.3) profiles and PAE properties, the integrated low-pH zone (ILPZ) value was obtained to predict HMW level at the VI step. The simulations were performed to examine the operating parameters, such as agitation speed, acid addition rate, and protein concentration of PAE, of the pilot scale (50-200L) runs. The conditions with predictions of no product aggregation risk were recommended to the real scale-up runs, resulted in 100% success rate of the consecutive 12 pilot-scale runs. This work demonstrated that the CFD-based HMW prediction model could be used as a tool to facilitate the scale up of the low-pH VI process directly from bench to pilot/production scale.

Glyphosate is the world’s most widely used herbicide. The commercial success of this molecule is due to its non-selectivity and its action, which would supposedly target specific biosynthetic pathways found mainly in plants. Multiple studies have however provided evidence for high sensitivity of many non-target species to glyphosate and/or to formulations (glyphosate mixed with surfactants). This herbicide, found at significant levels in aquatic systems through surface runoffs, impacts life history traits and immune parameters of several aquatic invertebrates’ species. Some of these species are vectors of diseases, one of the most important of which is the mosquito. Mosquitoes, from hatching to emergence, are exposed to aquatic chemical contaminants. In this study, we first compared the toxicity of pure glyphosate to the toxicity of glyphosate-based formulations for the main vector of avian malaria in Europe, Culex pipiens mosquito. Then we evaluated, for the first time, how field realistic dose of glyphosate interacts with larval nutritional stress to alter mosquito life history traits and susceptibility to avian malaria parasite infection. Our results show that exposure of larvae to field-realistic doses of glyphosate, pure or in formulation, did not affect larval survival rate, adult size and female fecundity. One of our two experimental blocks showed, however, that exposure to glyphosate decreased development time and reduced mosquito infection probability by malaria parasite. Interestingly the effect on malaria infection was lost when the larvae were also subjected to a nutritional stress, probably due to a lower ingestion of glyphosate.

Hydroxyl derivatives of cinnamic acid, both natural and synthetic, are well-known antioxidants. However, not all of them feature the same radical-scavenging propensity. Establishing the relation between structure and reactivity towards radical of those species plays a crucial role in the design of novel antioxidant pharmaceuticals founded on the same parent structure. The study aims at clarifying the relationship between topology, geometry, electron and spin density distribution and the radical-scavenging activity. Different mechanisms are discussed based on the enthalpies of the possible structures generated in the process of dissociation of the OH-bonds. All structures are modelled utilizing first principles methods and accounting for the polar medium at neutral pH (B3LYP/6-311++G**/PCM). A hybrid mechanism is suggested applicable not only to hydroxylated cinnamic acids but to phenolic acids in polar environment in general.

In this paper, a novel beam steerable 2.4 GHz MIMO antenna array is proposed based on the Yagi-Uda principle. The antenna consists of two co-axially excited patch radiators with modified ground plane. A conducting strip with an integrated PIN diode is optimally placed between the patch radiators to act as a director or a reflector to steer the main beam by an angle of +/- 60◦. For all switching modes, the MIMO antenna demonstrates an average gain and efficiency of 5 dB and 92%, respectively, at the resonance frequency of 2.4 GHz. Reduced envelope correlation coefficient in one switching mode exhibited 17 dB improvement in mutual isolation. The simulated results agreed well with measured data. This simple, low-cost, efficient, and mutually isolated antenna array can be very useful in MIMO WLAN applications.

The newly generalized energy storage component namely memristor is a fundamental circuit element so called universal charge-controlled mem-element is proposed for controlling the analysis and coexisting attractors. The governing differential equations of memristor are highly non-linear for mathematical relationships. The mathematical model of memristor is established in terms of newly defined fractal-fractional differential operators so called Atangana-Baleanu, Caputo-Fabrizio and Caputo fractal-fractional differential operator. A novel numerical approach is developed for the governing differential equations of memristor on the basis of Atangana-Baleanu, Caputo-Fabrizio and Caputo fractal-fractional differential operator. We discussed chaotic behavior of memristor under three criteria as (i) varying fractal order, we fixed fractional order, (ii) varying fractional order, we fixed fractal order and (ii) varying fractal and fractional orders simultaneously. Our investigated graphical illustrations and simulated results via MATLAB for the chaotic behaviors of memristor suggest that newly presented Atangana-Baleanu, Caputo-Fabrizio and Caputo fractal-fractional differential operator has generates significant results as compared with classical approach.

An SIS epidemic reaction-diffusion model with saturated incidence rate and spontaneous infection is considered. We establish the existence of endemic equilibrium by using a fixed point theorem. We mainly investigate the effects of diffusion and saturation on asymptotic profiles of the endemic equilibrium. Our analysis shows that the spontaneous infection can enhance persistence of infectious disease.

In this study, we investigate the sum-type singular nonlinear fractional q-integro-differential $m$-point boundary value problem. The existence of positive solutions is obtained by the properties of the Green function, standard Caputo $q$-derivative, Riemann-Liouville fractional $q$-integral and the means of a fixed point theorem on a real Banach space $(\mathcal{X}, \|.\|)$ which has a partially order by using a cone $P \subset \mathcal{X}$. The proofs are based on solving the operator equation $\mathcal{O}_1 x + \mathcal{O}_2 x = x $ such that the operator $\mathcal{O}_1$, $\mathcal{O}_2$ are $r$-convex, sub-homogeneous, respectively and define on cone $P$. As applications, we provide an example illustrating the primary effects.

We study properties of a piecewise deterministic Markov process modeling the changes in concentration of specific antibodies.The evolution of densities of the process is described by a stochastic semigroup. The long-time behaviour of this semigroup is studied. In particular we prove theorems on its asymptotic stability.

In this paper, we focus on designing a well-conditioned Glarkin spectral methods for solving a two-sided fractional diffusion equations with drift, in which the fractional operators are defined neither in Riemann-Liouville nor Caputo sense, and its physical meaning is clear. Based on the image spaces of Riemann-Liouville fractional integral operators on Lp([a, b]) space discussed in our previous work, after a step by step deduction, three kinds of Galerkin spectral formulations are proposed, the final obtained corresponding scheme of which shows to be well-conditioned—the condition number of the stiff matrix can be reduced from O(N2α) to O(Nα), where N is the degree of the polynomials used in the approximation. Another point is that the obtained schemes can also be applied successfully to approximate fractional Laplacian with generalized homogeneous boundary conditions, whose fractional order α ∈ (0, 2), not only having to be limited to α ∈ (1, 2). Several numerical experiments demonstrate the effectiveness of the derived schemes. Besides, based on the numerical results, we can observe the behavior of mean first exit time, an interesting quantity that can provide us with a further understanding about the mechanism of abnormal diffusion.

Environmental DNA (eDNA) is used for monitoring the occurrence of freshwater organisms. Various studies show a relation between the amount of eDNA detected and target organism abundance, thus providing a potential proxy for reconstructing population densities. However, environmental factors such as water temperature and microbial activity are known to affect the amount of eDNA present as well In this study, we use controlled aquarium experiments using Gammarus pulex L. (Amphipoda) to investigate the relationship between the amount of detectable eDNA through time, pH, and levels of organic material. We found eDNA to degrade faster when organic material was added to the aquarium water, but that pH had no significant effect. We infer that eDNA contained inside cells and mitochondria is extra resilient against degradation, though this may not reflect actual presence of target species. These results indicate that, although estimation of population density might be possible using eDNA, measured eDNA concentration could, in the future, be corrected for local environmental conditions in order to ensure accurate comparisons.

1. Terrestrial plant populations located at the margins of species’ distributions often display reduced sexual reproduction and an increased reliance on asexual reproduction. One hypothesis to explain this phenomenon is that the decline is associated with environmental effects on the energetic costs to produce reproductive organs. 2. In order to clarify the changing processes of sexual reproduction along an altitudinal gradient, we investigated the sexual reproductive parameters, such as the number of sporophytes and gametangia, in Racomitrium lanuginosum, a dioicous moss found on Mt. Fuji. Matured sporophytes were present only below 3000 m, and the number of sporophytes per shoot tended to be lower at higher altitudes. 3. The numbers of male inflorescences per shoot and antheridia per inflorescence and shoot significantly decreased with increasing altitude. In contrast, the numbers of female inflorescences per shoot and archegonia per inflorescence and shoot varied little across altitudes. 4. Synthesis. Our results suggest that the success of sexual reproduction in R. lanuginosum is restricted at higher altitudes on Mt. Fuji by decreases in male gametangia and the subsequent chance of fertilization. These differences between males and females may be caused by differences in the cost of production and development of gametangia, sensitivity to environmental stresses (low air temperature, shortened growth period, and environmental conditions in winter), and phenological patterns at higher altitudes.

Bubble formation from a downward-pointing capillary nozzle was investigated in this study. The experiments were conducted at gas flow rate of 40-5400 mL/h and inner nozzle radius of 0.030-0.255 mm. Experimental results show that microbubbles were formed continuously at moderate Weber number, which was not reported in pervious investigations with injecting gas through an upward-pointing capillary nozzle. High-speed visualization indicates that the formation of microbubbles arises from the convergence of the capillary waves induced by the partial coalescence of larger bubbles. A bubbling regime map is given to identify the critical conditions for the formation of microbubbles. In the present air-water experiments, the generated microbubbles are 20-170 μm in diameter. From experimental data, a scaling law for microbubble size is proposed as a function of Weber and Bond numbers.

Aim: Threats faced by narrowly distributed endemic plant species in the face of the Earth’s sixth mass extinction and climate change exposure are especially severe for taxa on islands. We investigated the current and projected distribution and range changes of Cochemiea halei, an island endemic cactus. This taxon is of conservation concern, currently listed as vulnerable on the International Union for the Conservation of Nature Red List and as a species of special concern under Mexican federal law. The goals of this study are to 1). identify the correlations between climate variables and current suitable habitat for C. halei; 2). determine if the species is a serpentine endemic or has a facultative relationship with ultramafic soils; 3). predict range changes of the species based on climate change scenarios. Location: The island archipelago in Bahía Magdalena on the Pacific coast, Baja California Sur, Mexico. Methods: We used temperature and precipitation variables at 30 arcsecond resolution and soil type, employing multiple species distribution modeling methods, to identify important climate and soil conditions driving current habitat suitability. The best model of current suitability is used to predict possible effects of four climate change scenarios based on best case to worst case representative concentration pathways, with projected climate data from two general circulation models, over two time periods. Main conclusions: The occurrence of the species is found to be strongly correlated with ultramafic soils. The most important climate predictor for habitat suitability is annual temperature range. The species is predicted to undergo range contractions from 21% to 53%, depending on the severity and duration of exposure to climate change. The broader implications for a wide range of narrowly adapted, threatened and endemic plant species indicate an urgent need for threat assessment based on habitat suitability and climate change modeling.

Bubble size distribution and bubble ellipticity were measured as a function of axial position in a vertically oriented semi-batch gas-liquid Taylor vortex reactor with varying gas flow rate and inner cylinder rotation speed producing axial Reynolds numbers in the range 23.8-119 and azimuthal Reynolds numbers up to 4.2×104. The mean bubble size increases monotonically with axial distance from the bottom of the reactor at the location of gas injection. The functional form of the growth of the mean bubble size with axial position depends upon the azimuthal Reynolds number. Specifically, when the azimuthal Reynolds number is less than 1.3×104, the mean bubble size increases linearly with axial distance from the bubble injection point. In contrast, for azimuthal Reynolds numbers greater than this critical value, the mean bubble size increases with axial distance in a sigmoidal manner.

Informative/Abstract:Estimating streamflow is time and labour intensive due to the necessity of developing a rating curve. The development of a rating curve involves acquiring at least thirty in-field measurements of streamflow across a wide range of flow levels, which can be costly and impractical in remote regions with limited seasonal access. Here we showcase an automated system which accurately estimates streamflow multiple times each day, greatly facilitating the development of rating curves for remote or seasonally inaccessible sites. The system uses an emerging technique referred to as particle image velocimetry (PIV) to track the movement of objects and flow structure features on the mobile water surface to generate velocity vector grids. Velocity grids were used to calculate streamflow and facilitate the development of a rating curve. This represents the first use of an automated PIV system to estimate streamflow in small streams (< 5 m wide) and the first system to automatically distribute particles for facilitated PIV analysis.Keywords: Particle Image Velocimetry, Streamflow Monitoring, Automated Systems, Particle TracerFunding: This research was funded through the Ministry of Natural Resources and Forestry, the Canada-Ontario Agreement Fund, and the Queen Elizabeth II Graduate Scholarship in Science and Technology.

A self-wiping co-rotating twin-screw extruder (TSE) is operated in a starved state where the screws are partially filled with resin. Understanding resin distribution on the screw surface is essential for the design, operation, and maintenance of the twin-screw extrusion process. In this study, the circumferential and axial distribution of pressure, temperature, and resin in a TSE are calculated using a novel method combining the mathematical formulation of Hele–Shaw flow, the finite element method, and a newly developed down-wind pressure update scheme. The experimental results were in good agreement with the measured results. This calculation method enables us to visualize, in detail, the resin distribution, pressure, and temperature for the entire axial and circumferential direction over the TSE.

In the biopharmaceutical industry, Raman spectroscopy is now a proven PAT tool that enables in-line simultaneous monitoring of several CPPs and CQAs in real-time. However, as Raman monitoring requires multivariate modeling, variabilities unknown by models can impact the monitoring prediction accuracy. With the widespread use of Raman PAT tools, it is necessary to fix instrumental variability impacts, encountered for instance during a device replacement. In this work, we investigated the impact of instrumental variability between probes inside a multi-channel analyzer and between two analyzers, and explored solutions to correct them on model prediction errors in cell cultures. We found that the Kennard Stone Piecewise Direct Standardization (KS PDS) method enables to lower model prediction errors and that only one batch with the unknown device in the calibration dataset was sufficient to correct the prediction gap induced by instrumental variability. As a matter of fact, during device replacement a first cell culture monitoring can be performed with the KS PDS method. Then, the new data obtained can be inserted in the calibration dataset to integrate instrumental variability in the chemometric model. This methodology provides good multivariate calibration model prediction errors throughout the instrumental changes.

Seasonal suspended sediment transfer in glaciated catchments is responsive to meteorological, geomorphological, and glacio-fluvial conditions, and thus is a useful indicator of environmental system dynamics. Knowledge of multifaceted fluvial sediment-transfer processes is limited in the Arctic–a region sensitive to contemporary environmental change. For two glaciated sub-catchments at Lake Peters, northeast Brooks Range, Alaska, we conducted a two-year endeavor to monitor the hydrology and meteorology, and used the data to derive multiple-regression models of suspended sediment load. Statistical selection of the best models shows that incorporating meteorological or temporal explanatory variables improves performances of turbidity- and discharge-based sediment models. The resulting modeled specific suspended sediment yields to Lake Peters are: 33 (20-60) Mg km-2 yr-1 in 2015, and 79 (50-140) Mg km-2 yr-1 in 2016 (95% confidence band estimates). In contrast to previous studies in Arctic Alaska, fluvial suspended sediment transfer to Lake Peters was primarily influenced by rainfall, and secondarily influenced by temperature-driven melt processes associated with clockwise diurnal hysteresis. Despite different sub-catchment glacier coverage, specific yields were the same order of magnitude from the two primary inflows to Lake Peters, which are Carnivore Creek (128 km2; 10% glacier coverage) and Chamberlin Creek (8 km2; 23% glacier coverage). Seasonal to longer term sediment exhaustion and/or contrasting glacier dynamics may explain the lower than expected relative specific sediment yield from the more heavily glacierized Chamberlin Creek catchment. Absolute suspended sediment yield (Mg yr-1) from Carnivore Creek to Lake Peters was 28 times greater than from Chamberlin Creek, which we attribute to catchment size and sediment supply differences. Our results are useful for predicting changes in fluvial sediment transport in glaciated Arctic catchments.