不同种植年限薰衣草根际土壤真菌群落结构的演变

土壤真菌群落结构和多样性对植物生长起着重要作用,了解种植年限对薰衣草根际土壤真菌群落结构的影响对薰衣草病害防治和增产的研究具有重要意义。探究不同种植年限薰衣草根际土壤真菌群落结构和多样性特征,及其随种植年限的演变规律。采集新疆伊犁霍城县种植年限1、3、5 a,以及未种植薰衣草土壤,对ITS序列进行Illumina高通量测序。对测序结果进行分析,比较各样品组真菌多样性和群落分布规律及与种植年限的关联。结果表明,Alpha多样性分析显示随着种植年限的增加Shannon指数逐渐降低,而Chao1指数先降低后增高。在种植薰衣草土壤中共检测到12个门,28个纲,72个目,146个科,236个属。在门水平上,子囊菌门(Ascomycota)、担子菌门(Basidiomycota)、球囊菌门(Glomeromycota)为优势菌门。随着种植年限的增加,子囊菌门相对丰度逐渐降低,担子菌门逐渐增高,而球囊菌门先增加后降低。在属水平上优势菌属为Xylodon、锐孔菌属(Oxyporus)、镰刀菌属(Fusarium)、枝孢属(Cladosporium),均属于植物致病菌。随着种植年限的增加,Xylodon...     

Protein fouling during constant-flux virus filtration: Mechanisms and modeling

As biomanufacturers consider the transition from batch to continuous processing, it will be necessary to re-examine the design and operating conditions for many downstream processes. For example, the integration of virus removal filtration in continuous biomanufacturing will likely require operation at low and constant filtrate flux instead of the high (constant) transmembrane pressures (TMPs) currently employed in traditional batch processing. The objective of this study was to examine the effect of low operating filtrate flux (5–100 L/m²/h) on protein fouling during normal flow filtration of human serum Immunoglobulin G (hIgG) through the Viresolve® Pro membrane, including a direct comparison of the fouling behavior during constant-flux and constant-pressure operation. The filter capacity, defined as the volumetric throughput of hIgG solution at which the TMP increased to 30 psi, showed a distinct minimum at intermediate filtrate flux (around 20–30 L/m²/h). The fouling data were well-described using a previously-developed mechanistic model based on sequential pore blockage and cake filtration, suitably modified for operation at constant flux. Simple analytical expressions for the pressure profiles were developed in the limits of very low and high filtrate flux, enabling rapid estimation of the filter performance and capacity. The model calculations highlight the importance of both the pressure-dependent rate of pore blockage and the compressibility of the protein cake to the fouling behavior. These results provide important insights into the overall impact of constant-flux operation on the protein fouling behavior and filter capacity during virus removal filtration using the Viresolve® Pro membrane.     

A classification model for continuous responses: Identifying risk perception groups on health-related activities

In the current literature on latent variable models, much effort has been put on the development of dichotomous and polytomous cognitive diagnostic models (CDMs) for assessments. Recently, the possibility of using continuous responses in CDMs has been brought to discussion. But no Bayesian approach has been developed yet for the analysis of CDMs when responses are continuous. Our work is the first Bayesian framework for the continuous deterministic inputs, noisy, and gate (DINA) model. We also propose new interpretations for item parameters in this DINA model, which makes the analysis more interpretable than before. In addition, we have conducted several simulations to evaluate the performance of the continuous DINA model through our Bayesian approach. Then, we have applied the proposed DINA model to a real data example of risk perceptions for individuals over a range of health-related activities. The application results exemplify the high potential of the use of the proposed continuous DINA model to classify individuals in the study.     

Modeling the Residence Time Distribution of Integrated Continuous Bioprocesses

In response to the biopharmaceutical industry advancing from traditional batch operation to continuous operation, the Food and Drug Administration (FDA) has published a draft for continuous integrated biomanufacturing. This draft outlines the most important rules for establishing continuous integration. One of these rules is a thorough understanding of mass flows in the process. A computer simulation framework is developed for modeling the residence time distribution (RTD) of integrated continuous downstream processes based on a unit‐by‐unit modeling approach in which unit operations are simulated one‐by‐one across the entire processing time, and then combined into an integrated RTD model. The framework allows for easy addition or replacement of new unit operations, as well as quick adjustment of process parameters during evaluation of the RTD model. With this RTD model, the start‐up phase to reach steady state can be accelerated, the effects of process disturbances at any stage of the process can be calculated, and virtual tracking of a section of the inlet material throughout the process is possible. A hypothetical biomanufacturing process for an antibody was chosen for showcasing the RTD modeling approach.     

Predator–prey interactions in the canopy

Small mammal abundances are frequently limited by resource availability, but predators can exert strong lethal (mortality) and nonlethal (e.g., nest abandonment) limitations. Artificially increasing resource availability for uncommon small mammals provides a unique opportunity to examine predator–prey interactions. We used remote cameras to monitor 168 nest platforms placed in the live tree canopy (n = 23 young forest stands), primarily for arboreal red tree voles (tree voles; Arborimus longicaudus), over 3 years (n = 15,510 monitoring‐weeks). Tree voles frequently built nests and were detected 37% of monitoring‐weeks, whereas flying squirrels (Glaucomys oregonensis) built nests infrequently but were detected 45% of monitoring‐weeks. Most nest predators were detected infrequently (<1% of monitoring‐weeks) and were positively correlated with tree vole presence. Weasels (Mustela spp.) were highly effective predators of tree voles (n = 8 mortalities; 10% of detections) compared to owls (n = 1), flying squirrels (n = 2), and Steller's jays (n = 1). Tree vole activity decreased from 84.1 (95% confidence interval [CI]: 56.2, 111.9) detections/week 1‐week prior to a weasel detection to 4.7 detections/week (95% CI: 1.7, 7.8) 1‐week postdetection and remained low for at least 12 weeks. Interpretations of predator–prey interactions were highly sensitive to how we binned continuously collected data and model results from our finest bin width were biologically counter‐intuitive. Average annual survival of female tree voles was consistent with a previous study (0.14; 95% CI: ?0.04 [0.01], 0.32) and high compared to many terrestrial voles. The relative infrequency of weasel detections and inefficiency of other predators did not provide strong support for the hypothesis that predation per se limited populations. Rather, predation pressure, by reducing occupancy of already scarce nest sites through mortality and nest abandonment, may contribute to long‐term local instability of tree vole populations in young forests. Additional monitoring would be needed to assess this hypothesis.     

Bayesian shrinkage estimation of high dimensional causal mediation effects in omics studies

Causal mediation analysis aims to examine the role of a mediator or a group of mediators that lie in the pathway between an exposure and an outcome. Recent biomedical studies often involve a large number of potential mediators based on high-throughput technologies. Most of the current analytic methods focus on settings with one or a moderate number of potential mediators. With the expanding growth of -omics data, joint analysis of molecular-level genomics data with epidemiological data through mediation analysis is becoming more common. However, such joint analysis requires methods that can simultaneously accommodate high-dimensional mediators and that are currently lacking. To address this problem, we develop a Bayesian inference method using continuous shrinkage priors to extend previous causal mediation analysis techniques to a high-dimensional setting. Simulations demonstrate that our method improves the power of global mediation analysis compared to simpler alternatives and has decent performance to identify true nonnull contributions to the mediation effects of the pathway. The Bayesian method also helps us to understand the structure of the composite null cases for inactive mediators in the pathway. We applied our method to Multi-Ethnic Study of Atherosclerosis and identified DNA methylation regions that may actively mediate the effect of socioeconomic status on cardiometabolic outcomes.     

Continuous ultrafiltration/diafiltration using a 3D-printed two membrane single pass module

A 3D printed ultrafiltration/diafiltration (UF/DF) module is presented allowing the continuous, simultaneous concentration of retained (bio-)molecules and reduction or exchange of the salt buffer. Differing from the single-pass UF concepts known from the literature, DF operation does not require the application of several steps or units with intermediating dilution. In contrast, the developed module uses two membranes confining the section in which the molecules are concentrated while the sample is passing. Simultaneously to this concentration process, the two membranes allow a perpendicular in and outflow of DF buffer reducing the salt content in this section. The module showed the continuous concentration of a dissolved protein up to a factor of 4.6 while reducing the salt concentration down to 47% of the initial concentration along a flow path length of only 5 cm. Due to single-pass operation the module shows concentration polarization effects reducing the effective permeability of the applied membrane in case of higher concentration factors. However, because of its simple design and the capability to simultaneously run UF and DF processes in a single module, the development could be economically beneficial for small scale UF/DF applications.     

Simulation of pH level distribution inside a coiled flow inverter for continuous low pH viral inactivation

The continuous production of monoclonal antibodies (mAbs) with the help of disposable equipment poses one of the future major changes in the pharmaceutical industry. Consequently, continuous viral clearance needs to be developed as well. The coiled flow inverter (CFI) was successfully implemented in the continuous downstream as a residence time module for low pH viral inactivation. As the elution profile of the upstream continuously operated protein A chromatography results in fluctuating pH values, the pH level distribution inside the CFI is highly relevant. This study presents a detailed investigation of pH level distribution inside the CFI at varying inlet conditions with the help of computational fluid dynamics simulation. The simulation model was validated first with the help of experimental data. Afterwards, the model was used for further investigations. It was determined that with a pH sine curve as input, the duration until steady state at the outlet requires two times the minimum residence time of the apparatus. Moreover, it could be observed that the CFI itself offers a progressive dampening effect on the pH level distribution. Afterwards, different forms of the sine curve representing different operation modes of the continuous protein A chromatograph were tested to evaluate this dampening capability. It became clear that the switch time has the highest influence on the resulting pH of the outlet stream and should be considered for process development. Finally, the radial pH profiles at different positions inside the CFI were determined. This once again revealed the high radial mixing capability of the CFI and its influence on the resulting product stream.     

Novel spiking methods developed for anion exchange chromatography operating in a continuous process

Many manufacturers of biopharmaceuticals are moving from batch to continuous processing. While this approach offers advantages over batch processing, demonstration of viral clearance for continuous processes is challenging. Fluctuating output from a continuous process chromatography column results in a nonhomogeneous load for the subsequent column and must be considered when designing viral clearance studies. One approach to clearance studies is to downscale the connected unit operations and introduce virus by in-line spiking. This is challenging to be implemented at the contract research organization performing the clearance study given the complexity of systems and level of expertise required. Alternately, each unit operation could be evaluated in traditional batch mode but the spiking and loading conditions be modified to mimic the variance introduced by the transition between two connected columns. Using a standard chromatography system, we evaluated a flow-through anion exchange chromatography step in a monoclonal antibody (mAb) manufacturing process using five different methods to introduce the virus to the column. Our data show that whether the virus or the mAbs were introduced in concentrated peaks, or as a homogeneous batch, the clearance of mouse minute virus was similar. This study introduces an alternative way to evaluate viral clearance in a continuous process and demonstrates the robustness of anion exchange chromatography unit operating in continuous processing.     

Prevalence and Clinical Determinants of Obesity in Adults With Type 1 Diabetes Mellitus: A Single-Center Retrospective Observational Study

ObjectiveTo determine the prevalence of obesity and assess the cardiometabolic risk profile and treatments associated with obesity management in the type 1 diabetes mellitus adult population.MethodsWe reviewed the records of all patients with type 1 diabetes mellitus seen in our institution’s outpatient endocrinology clinic between 2015 and 2018. We stratified the patients into 4 weight categories on the basis of body mass index (BMI) (normal, overweight, obesity class I, and combined obesity class II and III) and evaluated their associated clinical characteristics and relevant medications.ResultsOf 451 patients, 64% had a BMI of >25 kg/m², and 25% had a BMI of ≥30 kg/m². Over 40% of patients with a BMI of >30 kg/m² had a history of cardiovascular disease. The off-label use of the glucagon-like peptide 1 receptor agonist was 12% and the sodium glucose cotransporter 2 inhibitor use was 5% in those with obesity. Only 2 patients were prescribed phentermine and 3 had undergone bariatric surgery. Hemoglobin A1C and low-density lipoprotein did not significantly differ between the normal weight and obesity groups. The obesity groups had significantly higher levels of median triglycerides and lower high-density lipoprotein than the normal weight group.ConclusionObesity was prevalent in a population of patients with type 1 diabetes mellitus seen in a specialty clinic. Those with obesity had a higher prevalence of cardiovascular disease than their normal weight counterparts. The use of weight loss medications was scarce. Studies exploring the safety and efficacy of obesity-targeted therapy in the type 1 diabetes mellitus population are needed.