Automated methods for accurate determination of the critical velocity of packed bed chromatography

Knowing the critical velocity (ucrit) of a chromatography column is an important part of process development as it allows the optimization of chromatographic flow conditions. The conventional flow step method for determining ucrit is prone to error as it depends heavily on human judgment. In this study, two automated methods for determining ucrit have been developed: the automatic flow step (AFS) method and the automatic pressure step (APS) method. In the AFS method, the column pressure drop is monitored upon application of automated incremental increases in flow velocity, whereas in the APS method the flow velocity is monitored upon application of automated incremental increases in pressure drop. The APS method emerged as the one with the higher levels of accuracy, efficiency and ease of application having the greater potential to assist defining the best operational parameters of a chromatography column.     

Radionuclide plethysmography for noninvasive evaluation of peripheral arterial blood flow

We validated a noninvasive radionuclide plethysmography technique to evaluate peripheral arterial blood flow during reactive hyperemia. This method, based on the measurement of blood volume variations during repetitive venous occlusions, was compared with strain-gauge venous impedance plethysmography. The technique uses 99mTc-labeled autologous red blood cells scintigraphy to determine the rate of change of forearm scintigraphic counts during venous occlusion. Thirteen subjects were simultaneously evaluated with radionuclide and impedance plethysmography. Six baseline flow measurements were performed to evaluate the reproducibility of each method. Twenty-seven serial measurements were then made to evaluate flow variation during forearm reactive hyperemia. After 30 min of recovery, resting forearm blood flows were again evaluated. Impedance and radionuclide methods showed excellent reproducibility with intraclass correlation coefficients of 0.96 and 0.93, respectively. There was also good correlation of flows between both methods during reactive hyperemia (r = 0.87). Resting flows at 30 min after reactive hyperemia were slightly lower than at baseline with both methods. We conclude that radionuclide plethysmography could be used for the noninvasive evaluation of forearm blood flow and its dynamic variations during reactive hyperemia.     

Identifying Indices of Learning for Alpha Neurofeedback Training

Neurofeedback has been around for decades and has applications for both clinical and healthy populations yet there is no standard method for measuring learning or a way of defining successful learning. Thus the aim of this study was to focus on alpha neurofeedback and examine changes in three different measures: amplitude, percent time, and integrated alpha, across four methods: within sessions, across sessions, within sessions compared to baseline, and across sessions compared to baseline. Participants completed 10 weekly sessions of eyes open alpha (8–12 Hz) neurofeedback training (NFT) at Pz. Whilst all three measures showed changes within sessions, the inclusion of baselines revealed that such changes represented a return to baseline levels rather than an increase in alpha. Changes across sessions were only evident in amplitude and inclusion of baseline showed that NFT did not elicit any changes beyond baseline levels. Given this a case is made for incorporating baseline measures when attempting to identify evidence of learning. It is also suggested that both amplitude and percent time measures are used independently rather than incorporate them into a more conservative and less sensitive integrated measure. Finally, focusing on within sessions changes may be a more useful approach in identifying changes resulting from NFT.     

Simulation of pressure drop and energy dissipation for blood flow in a human fetal bifurcation.

The pressure drop from the umbilical vein to the heart plays a vital part in human fetal circulation. The bulk of the pressure drop is believed to take place at the inlet of the ductus venosus, a short narrow branch of the umbilical vein. In this study a generalized Bernoulli formulation was deduced to estimate this pressure drop. The model contains an energy dissipation term and flow-scaled velocities and pressures. The flow-scaled variables are related to their corresponding spatial mean velocities and pressures by certain shape factors. Further, based on physiological measurements, we established a simplified, rigid-walled, three-dimensional computational model of the umbilical vein and ductus venosus bifurcation for stationary flow conditions. Simulations were carried out for Reynolds numbers and umbilical vein curvature ratios in their respective physiological ranges. The shape factors in the Bernoulli formulation were then estimated for our computational models. They showed no significant Reynolds number or curvature ratio dependency. Further, the energy dissipation in our models was estimated to constitute 24 to 31 percent of the pressure drop, depending on the Reynolds number and the curvature ratio. The energy dissipation should therefore be taken into account in pressure drop estimates.     

Evaluation of an enzyme immunoassay technique for the detection of salmonellas in minced meat

A comparison was made between a commercially available enzyme immunoassay (ELISA) and various cultural procedures for detecting salmonellas in minced meat contaminated with a standard inoculum. To detect salmonellas by the ELISA technique, it was necessary to modify the recommended baseline for spectrophotometric measurements to avoid false-positive results. The incidence of false-negatives was no greater than that obtained with a standard isolation procedure. Both methods were affected by the competing microflora.     

Investigating assumptions of vulnerability: A case study of the exclusion of psychiatric inpatients as participants in genetic research in low‐ and middle‐income contexts

Psychiatric genetic research investigates the genetic basis of psychiatric disorders with the aim of more effectively understanding, treating, or, ultimately, preventing such disorders. Given the challenges of recruiting research participants into such studies, the potential for long‐term benefits of such research, and seemingly minimal risk, a strong claim could be made that all non‐acute psychiatric inpatients, including forensic and involuntary patients, should be included in such research, provided they have capacity to consent. There are tensions, however, regarding the ethics of recruiting psychiatric inpatients into such studies. In this paper our intention is to elucidate the source of these tensions from the perspective of research ethics committee interests and decision‐making. We begin by defining inpatient status and outline some of the assumptions surrounding the structures of inpatient care. We then introduce contemporary conceptions of vulnerability, including Florencia Luna’s account of vulnerability which we use as a framework for our analysis. While psychiatric inpatients could be subject to consent‐related vulnerabilities, we suggest that a particular kind of exploitation‐related vulnerability comes to the fore in the context of our case study. Moreover, a subset of these ethical concerns takes on particular weight in the context of genetic research in low‐ and middle‐income countries. At the same time, the automatic exclusion of inpatients from research elicits justice‐related vulnerabilities.     

Fatigue of the plantar intrinsic foot muscles increases navicular drop

Our purpose was to assess the effect of foot intrinsic muscle fatigue on pronation, as assessed with navicular drop, during static stance. Twenty-one healthy young adults participated. Navicular drop was measured before and after fatiguing exercise of the plantar foot intrinsic muscles. Surface electromyography of the abductor hallucis muscle was recorded during maximum voluntary isometric contractions (MVIC) in order to find the baseline median frequency (MedF). Subjects then performed sets of 75 repetitions of isotonic flexion contractions of the intrinsic foot muscles against a 4.55 kg weight on a custom pulley system. After each set an MVIC was performed to track shifts in MedF. After a MedF shift of at least 10%, navicular drop measurements were repeated. Subjects exhibited 10.0 ± 3.8 mm of navicular drop at baseline and 11.8 ± 3.8 mm after fatigue (p < 0.0005). The change in navicular drop was significantly correlated with change in MedF (r = .47, p = .03). The intrinsic foot muscles play a role in support of the medial longitudinal arch in static stance. Disrupting the function of these muscles through fatigue resulted in an increase in pronation as assessed by navicular drop.     

三种判定落叶阔叶混交林土壤损害基线的方法研究——以吉林省抚松县为例

生态环境损害鉴定评估是生态系统修复与保护管理工作的基础,而生态环境损害基线作为一个地区生态水平原始状态的表征,是鉴定评估生态环境损害的基准。森林土壤是森林生态系统的重要组成部分,是维系森林生态系统生物及化学循环的关键部分,同时也是森林生态系统是否受到损害及损害程度大小的重要表征指标。在已有的生态环境损害基线判定方法的基础上,针对森林土壤的特点,改进森林土壤损害基线的判定方法并用这些方法对吉林省长白山抚松县地区落叶阔叶混交林进行研究。运用的3种方法包括群体分布法、三分位法和回归模型法。计算结果显示,运用三分位法确定的基线值最高,运用群体分布法确定的基线值最低。从方法的适用范围考虑,群体分布法和三分位法计算简便,结果可比性强,适用于无明显人为干扰的地区;回归模型法灵活度高,应用性广,适用于有较强人为干扰的地区;在数据充足的情况下应首选回归模型法,在回归模型法无法确认基线时,另外两种方法作为补充。     

Mixture-of-Experts Variational Autoencoder for clustering and generating from similarity-based representations on single cell data

Clustering high-dimensional data, such as images or biological measurements, is a long-standing problem and has been studied extensively. Recently, Deep Clustering has gained popularity due to its flexibility in fitting the specific peculiarities of complex data. Here we introduce the Mixture-of-Experts Similarity Variational Autoencoder (MoE-Sim-VAE), a novel generative clustering model. The model can learn multi-modal distributions of high-dimensional data and use these to generate realistic data with high efficacy and efficiency. MoE-Sim-VAE is based on a Variational Autoencoder (VAE), where the decoder consists of a Mixture-of-Experts (MoE) architecture. This specific architecture allows for various modes of the data to be automatically learned by means of the experts. Additionally, we encourage the lower dimensional latent representation of our model to follow a Gaussian mixture distribution and to accurately represent the similarities between the data points. We assess the performance of our model on the MNIST benchmark data set and challenging real-world tasks of clustering mouse organs from single-cell RNA-sequencing measurements and defining cell subpopulations from mass cytometry (CyTOF) measurements on hundreds of different datasets. MoE-Sim-VAE exhibits superior clustering performance on all these tasks in comparison to the baselines as well as competitor methods.     

Investigations on the surveys of office environments and the total evaluation method—IAQ-Index

1. 1. A comprehensive study was made to establish evaluation methods for better office environments.

2. 2. In our study, measurements of thermal, acoustic, lighting, airflow and air quality conditions in indoor environments were made as well as questionnaire to the occupants on the evaluations of indoor environments and the feeling of fatigue.

3. 3. We also made an attempt to rate the evaluation value based on concepts and standards to evaluate totally office environments in a view point of “the office environments where people can work healthy and vigorously”. The evaluation values were called IAQ-index.

Comparison of dental measurement systems for taxonomic assignment of first molars

Morphometrics of the molar crown is based traditionally on diameter measurements but is nowadays more often based on 2D image analysis of crown outlines. An alternative approach involves measurements at the level of the cervical line. We compare the information content of the two options in a three-dimensional (3D) digital sample of lower and upper first molars (M(1) and M(1) ) of modern human and Neanderthal teeth. The cervical outline for each tooth was created by digitizing the cervical line and then sectioning the tooth with a best fit plane. The crown outline was projected onto this same plane. The curves were analyzed by direct extraction of diameters, diagonals, and area and also by principal component analysis either of the residuals obtained by regressing out these measurements from the radii (shape information) or directly by the radii (size and shape information). For M(1) , the crown and cervical outline radii allow us to discriminate between Neanderthals and modern humans with 90% and 95% accuracy, respectively. Fairly good discrimination between the groups (80-82.5%) was also obtained using cervical measurements. With respect to M(1) , general overlap of the two groups was obtained by both crown and cervical measurements; however, the two taxa were differentiable by crown outline residuals (90-97%). Accordingly, while crown diameters or crown radii should be used for taxonomic analysis of unworn or slightly worn M(1) s, the crown outline, after regressing out size information, could be promising for taxonomic assignment of lower M1s.     

Cell density dependence of the aggregation characteristics of the cellular slime mould Dictyostelium discoideum.

We have measured fruiting body density and spore formation efficiency in Dictyostelium discoideum as functions of initial cell density. Experiments were performed on agar made up with distilled water and on buffered agar. Minor differences are seen; these are discussed. The functions show 4 regions of density dependence which can be accounted for by changes in aggregation characteristics with density and changes in the efficiency of spore differentiation. The results are discussed in terms of the relaying mechanism for signal propagation controlling cell aggregation. They extend earlier measurements by Bonner & Dodd and by Hohl & Raper, supply data for a quantitative model of the aggregation process, allow estimates of signal range, and show the importance of entrainment between neighbouring centres in defining aggregation territories.     

DNA sequence-dependent deformability--insights from computer simulations

The article reviews some recent developments in studying DNA sequence-dependent deformability, with emphasis on computer modeling. After a brief outline of available experimental techniques, we proceed to computational methods and focus on atomic-resolution molecular dynamics (MD) simulations. A sequence-dependent local (base-pair step) force field inferred from MD is compared with force fields obtained by other techniques. Various methods for establishing global (flexible-rod) DNA elastic constants are reviewed, including an approach based on atomic resolution MD. The problem of defining the global deformation variables, as well as the question of anisotropy and nonlocal effects, are discussed. As an example, both local and global deformability calculations from atomic-resolution MD of EcoRI dodecamer are presented.     

The mechanism distinguishability problem in biochemical kinetics: the single-enzyme, single-substrate reaction as a case study

A theoretical analysis of the distinguishability problem of two rival models of the single enzyme-single substrate reaction, the Michaelis-Menten and Henri mechanisms, is presented. We also outline a general approach for analysing the structural indistinguishability between two mechanisms. The approach involves constructing, if possible, a smooth mapping between the two candidate models. Evans et al. [N.D. Evans, M.J. Chappell, M.J. Chapman, K.R. Godfrey, Structural indistinguishability between uncontrolled (autonomous) nonlinear analytic systems, Automatica 40 (2004) 1947-1953] have shown that if, in addition, either of the mechanisms satisfies a particular criterion then such a transformation always exists when the models are indistinguishable from their experimentally observable outputs. The approach is applied to the single enzyme-single substrate reaction mechanism. In principle, mechanisms can be distinguished using this analysis, but we show that our ability to distinguish mechanistic models depends both on the precise measurements made, and on our knowledge of the system prior to performing the kinetics experiments.     

A review of age determination methods for the Stoat Mustela erminea

A sample of 166 Stoats collected from Craigieburn Forest Park, Canterbury, New Zealand, was used to assess the usefulness of seven different methods of age determination. All the methods made use of characters which do change with age, but not all are equally good at defining useful age classes. The recommended approach is to use a combination of skull and baculum measurements to identify young animals, followed by counting of the canine cementum annuli of adults. If the skull or baculum is broken or not available, visual assessment of the status of the nasal sutures, the lateral suprasesamoid tubercle of the femur and the wear of the carnassial teeth are the next best options for distinguishing the young. Kopein's index based on the closure of the pulp cavity of the canines, and the zonation visible in the periosteal bone of the mandible, are unreliable.     

Cooperative Aspects of Small Ion, Small Molecule Interactions with Nucleic Acids: Potassium-Polyriboadenylic Acid, Polyribouridylic Acid

Ionic conductivity measurements vs. temperature were made on KCl solutions of K-polyriboadenylic acid + K-polyribouridylic acid (K-poly-A + K-poly-U) in regions of temperature and composition where the helix-coil transition occurred. It was possible to relate the measurements to a differential helix-to-coil binding of K⁺ to nucleotide. The results were, within experimental error, the same as those obtained from a limited number of differential KCl activity coefficient measurements and from a theoretical interpretation of polymer free-boundary electrophoretic mobilities. It was concluded that the alkali ion-phosphate interaction in polynucleotides must be regarded as cooperative in nature and several criteria for recognition of such phenomena were given. A brief outline for a proposed statistical mechanical model for binding was presented.