Unholey shoes: Experimental considerations when estimating ankle joint complex power during walking and running

For studies that aim to assess biological ankle function, calculating ankle joint complex (AJC) power between the calcaneus and shank is recommended over conventional inverse dynamics estimates between a rigid-body foot and shank. However, when designing a new experiment, it remains unclear whether holes should be cut in footwear to permit motion tracking via skin-mounted markers, or whether marker placement locations should be tightly controlled across conditions. Here we provide data to assist researchers in answering these questions. We performed a gait analysis study of walking (0.8, 1.2, 1.6 m·s⁻¹) and running (2.6, 2.8, 3.0 m·s⁻¹) while subjects (N = 10) wore custom-modified footwear, which allowed markers to be placed either on the shoe, or on the skin via cut-out windows in the shoes. First, we compared foot markers affixed to the skin vs. on the same locations on the shoe. Using statistical non-parametric mapping techniques, we discovered that skin vs. shoe markers had no statistically significant effect on net AJC power estimates throughout stance phase, for all walking and running speeds. Second, we compared calcaneal markers in the nominal shoe configuration vs. markers in a nearby location (∼27 mm below) on the shoe. We observed significant differences when marker placement on the shoe was varied, which may be relevant to repeated-measures study designs. The results suggest that when computing AJC power for walking and running, you may want to put down the scissors (i.e., forego cutting holes in your footwear), and instead pick up a Sharpie® (pen) or use a template, to maintain consistent marker placement across trials and conditions.     

Distributions of the use frequencies of amino acids in the hypervariable regions of immunoglobulins

Two types of distributions for the frequencies of occurrence of amino acids in each position of hypervariable regions CDR-1 and CDR-2 were obtained for 2,000 immunoglobulins. The results show that some positions fit an inverse power-law distribution, while others fit an exponential-type distribution. As a result of comparison with structural data in the literature it is proposed that sites in which the frequency distribution fits the inverse power law are critical to maintaining canonical shapes of the recognition regions or are involved in modulating these canonical conformations, while those sites where the distribution fits the exponential law are those which should be exclusively involved in the recognition mechanism. Correspondence to: F. Lara-Ochoa     

Ankle and foot power in gait analysis: Implications for science,technology and clinical assessment

In human gait analysis studies, the entire foot is typically modeled as a single rigid-body segment; however, this neglects power generated/absorbed within the foot. Here we show how treating the entire foot as a rigid body can lead to misunderstandings related to (biological and prosthetic) foot function, and distort our understanding of ankle and muscle-tendon dynamics. We overview various (unconventional) inverse dynamics methods for estimating foot power, partitioning ankle vs. foot contributions, and computing combined anklefoot power. We present two case study examples. The first exemplifies how modeling the foot as a single rigid-body segment causes us to overestimate (and overvalue) muscle-tendon power generated about the biological ankle (in this study by up to 77%), and to misestimate (and misinform on) foot contributions; corroborating findings from previous multi-segment foot modeling studies. The second case study involved an individual with transtibial amputation walking on 8 different prosthetic feet. The results exemplify how assuming a rigid foot can skew comparisons between biological and prosthetic limbs, and lead to incorrect conclusions when comparing different prostheses/interventions. Based on analytical derivations, empirical findings and prior literature we recommend against computing conventional ankle power (between shank-foot). Instead, we recommend using an alternative estimate of power generated about the ankle joint complex (between shank-calcaneus) in conjunction with an estimate of foot power (between calcaneus-ground); or using a combined anklefoot power calculation. We conclude that treating the entire foot as a rigid-body segment is often inappropriate and ill-advised. Including foot power in biomechanical gait analysis is necessary to enhance scientific conclusions, clinical evaluations and technology development.     

Getting in shape: Reconstructing three-dimensional long-track speed skating kinematics by comparing several body pose reconstruction techniques

In gait studies body pose reconstruction (BPR) techniques have been widely explored, but no previous protocols have been developed for speed skating, while the peculiarities of the skating posture and technique do not automatically allow for the transfer of the results of those explorations to kinematic skating data. The aim of this paper is to determine the best procedure for body pose reconstruction and inverse dynamics of speed skating, and to what extend this choice influences the estimation of joint power. The results show that an eight body segment model together with a global optimization method with revolute joint in the knee and in the lumbosacral joint, while keeping the other joints spherical, would be the most realistic model to use for the inverse kinematics in speed skating. To determine joint power, this method should be combined with a least-square error method for the inverse dynamics. Reporting on the BPR technique and the inverse dynamic method is crucial to enable comparison between studies. Our data showed an underestimation of up to 74% in mean joint power when no optimization procedure was applied for BPR and an underestimation of up to 31% in mean joint power when a bottom-up inverse dynamics method was chosen instead of a least square error approach. Although these results are aimed at speed skating, reporting on the BPR procedure and the inverse dynamics method, together with setting a golden standard should be common practice in all human movement research to allow comparison between studies.     

The Sholl analysis of neuronal cell images: semi-log or log-log method?

Although the Sholl analysis is a quantitative method for morphometric neuronal studies and its application provides many benefits to neurobiology since it is obvious, common and meaningful, there are many unresolved theoretical issues that need to be addressed. Nevertheless, it can be practiced without much background or sophistication. The two different methods of the Sholl analysis--log-log and semi-log--have been applied previously without a clear basis as to what to use. To make an adequate choice of the method, one should try and accept that one which gives a better result. We consider that some of the underlying principles, assumptions and limitations for the Sholl analysis can be found in basic mathematics. In order to compare the results of applications of the semi-log and log-log methods to the same neuron, we introduce the concept of determination ratio as the ratio of the coefficient of determination for the semi-log method and that for the log-log method. If the semi-log method is better as related to the log-log method, the value of this parameter is larger than 1. Having in mind that dendrites exhibit enormously diverse forms, we point out that the semi-log Sholl method is more frequently utilizable in practice. Only the neurons, whose dendritic trees have one or a few sparsely ramified dendrites being much longer than the rest ones, could be successfully and exactly analysed using the log-log method. We also compare the Sholl analysis with fractal analysis for the characterization of neuronal arborization patterns and found that between the Sholl and fractal analysis exist various and important analogies.     

Scaling properties of childhood infectious diseases epidemics before and after mass vaccination in Canada

The goal of this paper is to analyse the scaling properties of childhood infectious disease time-series data. We present a scaling analysis of the distribution of epidemic sizes of measles, rubella, pertussis, and mumps outbreaks in Canada. This application provides a new approach in assessing infectious disease dynamics in a large vaccinated population. An inverse power-law (IPL) distribution function has been fit to the time series of epidemic sizes, and the results assessed against an exponential benchmark model. We have found that the rubella epidemic size distribution and that of measles in highly vaccinated periods follow an IPL. The IPL suggests the presence of a scale-invariant network for these diseases as a result of the heterogeneity of the individual contact rates. By contrast, it was found that pertussis and mumps were characterized by a uniform network of transmission of the exponential type, which suggests homogeneity in the contact rate or, more likely, boiled down heterogeneity by large intermixing in the population. We conclude that the topology of the network of infectious contacts depends on the disease type and its infection rate. It also appears that the socio-demographic structure of the population may play a part (e.g. pattern of contacts according to age) in the structuring of the topology of the network. The findings suggest that there is relevant information hidden in the variation of the common contagious disease time-series data, and that this information can have a bearing on the strategy of vaccination programs.     

A constrained extended Kalman filter for the optimal estimate of kinematics and kinetics of a sagittal symmetric exercise

This paper presents a method for real-time estimation of the kinematics and kinetics of a human body performing a sagittal symmetric motor task, which would minimize the impact of the stereophotogrammetric soft tissue artefacts (STA). The method is based on a bi-dimensional mechanical model of the locomotor apparatus the state variables of which (joint angles, velocities and accelerations, and the segments lengths and inertial parameters) are estimated by a constrained extended Kalman filter (CEKF) that fuses input information made of both stereophotogrammetric and dynamometric measurement data. Filter gains are made to saturate in order to obtain plausible state variables and the measurement covariance matrix of the filter accounts for the expected STA maximal amplitudes. We hypothesised that the ensemble of constraints and input redundant information would allow the method to attenuate the STA propagation to the end results. The method was evaluated in ten human subjects performing a squat exercise. The CEKF estimated and measured skin marker trajectories exhibited a RMS difference lower than 4 mm, thus in the range of STAs. The RMS differences between the measured ground reaction force and moment and those estimated using the proposed method (9 N and 10 N m) were much lower than obtained using a classical inverse dynamics approach (22 N and 30 N m). From the latter results it may be inferred that the presented method allows for a significant improvement of the accuracy with which kinematic variables and relevant time derivatives, model parameters and, therefore, intersegmental moments are estimated.     

Inverse Sampling in Case Control Studies Involving a Rare Exposure

In case-control studies where the outcome is not uncommon but the exposure is rare, inverse sampling may be used to reduce the total number of subjects required to find a fixed number of exposed cases and controls. The sampling distribution is negative binomial rather than binomial. Logistic regression for adjustment of covariates may be implemented on the computer program GLIM by the appropriate use of macros. An example is given.     

Pivotal surfaces in inverse hexagonal and cubic phases of phospholipids and glycolipids

Data on the location and dimensions of the pivotal surfaces in inverse hexagonal (H_II) and inverse cubic (Q_II) phases of phospholipids and glycolipids are reviewed. This includes the H_II phases of dioleoyl phosphatidylethanolamine, 2:1 mol/mol mixtures of saturated fatty acids with the corresponding diacyl phosphatidylcholine, and glucosyl didodecylglycerol, and also the Q_II^230/G gyroid inverse cubic phases of monooleoylglycerol and glucosyl didodecylglycerol. Data from the inverse cubic phases are largely compatible with those from inverse hexagonal H_II-phases. The pivotal plane is located in the hydrophobic region, relatively close to the polar–apolar interface. The area per lipid at the pivotal plane is similar in size to lipid cross-sectional areas found in the fluid lamellar phase (L_α) of lipid bilayers.     

基于模拟退火法由脑磁图推测电流偶极子参数

利用模拟退火（Ｓｉｍｕｌａｔｅｄ Ａｎｎｅａｌｉｎｇ） 算法,由脑磁图（ ＭＥＧ） 数据反演脑内作为磁源的单电流偶极子参数,可以得到理想的结果。在上述工作的基础上,对脑内多电流偶极子参数的反演,则呈现如下状况：即以少于实际源数目的偶极子为源假设反演,目标函数得不到极小优化。反之,目标函数可以得到极小优化, 但出现多余的伪偶极子, 且这些伪偶极子在多次不同条件的反演结果中,处于不稳定状态。若将多次反演结果中处于不稳定状态的偶极子作为伪偶极子的判据而将其排除,则可以得到一种判断磁源偶极子数目的方法     

A data-driven model of the generation of human EEG based on a spatially distributed stochastic wave equation

We discuss a model for the dynamics of the primary current density vector field within the grey matter of human brain. The model is based on a linear damped wave equation, driven by a stochastic term. By employing a realistically shaped average brain model and an estimate of the matrix which maps the primary currents distributed over grey matter to the electric potentials at the surface of the head, the model can be put into relation with recordings of the electroencephalogram (EEG). Through this step it becomes possible to employ EEG recordings for the purpose of estimating the primary current density vector field, i.e. finding a solution of the inverse problem of EEG generation. As a technique for inferring the unobserved high-dimensional primary current density field from EEG data of much lower dimension, a linear state space modelling approach is suggested, based on a generalisation of Kalman filtering, in combination with maximum-likelihood parameter estimation. The resulting algorithm for estimating dynamical solutions of the EEG inverse problem is applied to the task of localising the source of an epileptic spike from a clinical EEG data set; for comparison, we apply to the same task also a non-dynamical standard algorithm.     

反向PCR方法克隆腾冲嗜酸两面菌的分子伴侣基因

根据已知的Sulfolobus属的分子伴侣基因,设计简并引物,用PCR的方法从腾冲嗜酸两面菌（Acidianus tengchongensis）基因组DNA中分别克隆到了分子伴侣α亚基和β亚基的约500bp的基因片段。以它们为探针进行Southern杂交,确定了合适的限制性内切酶。以确定的限制性内切酶消化的基因组DNA环化物为模板,进行反向PCR反应,引物的延伸方向由已知序列出发沿环化分子向未知区域进行,扩增产物经测序表明为α亚基和β亚基基因。根据所得序列分别设计两对引物进行PCR,测序结果表明得到了α亚基和β亚基的完整基因。     

反向激动剂：受体研究中的一个新发现

静息时就有一部分受体处于激活性状它们与非激活状态的受体处于动态平衡状态之中。某些原来认为的受体拮抗对Ｒ的亲和性远远高于对Ｒ的亲和性,导致动态平衡中的Ｒ数量减少,因而产生生物效应,对某些受体突变或爱 体过度表达引起的疾病,反向激动剂具有应用前景。     

Molecular cloning and sequence analysis of the glyceraldehyde-3-phosphate dehydrogenase gene from the violet root rot fungus, <Emphasis Type="Italic">Helicobasidium mompa</Emphasis>

The glyceraldehyde-3-phosphate dehydrogenase (gpd) gene was cloned from the violet root rot fungus, Helicobasidium mompa, and characterized. Only one copy of the gene was present in the genome of H. mompa. The H. mompa gpd gene was found to encode a protein of 335 amino acids and its putative protein showed high homology with GPD protein from other heterobasidiomycetes. Although the promoter region contains a TATA box and several common motifs, these sequence positions were very different from that of other basidiomycetes. Moreover, mRNA expression showed that the gpd gene was transcribed constitutively in H. mompa.     

Lower limb joint work and joint work contribution during downhill and uphill walking at different inclinations

Work performance and individual joint contribution to total work are important information for creating training protocols, but were not assessed so far for sloped walking. Therefore, the purpose of this study was to analyze lower limb joint work and joint contribution of the hip, knee and ankle to total lower limb work during sloped walking in a healthy population. Eighteen male participants (27.0 ± 4.7 yrs, 1.80 ± 0.05 m, 74.5 ± 8.2 kg) walked on an instrumented ramp at inclination angles of 0°, ±6°, ±12° and ±18° at 1.1 m/s. Kinematic and kinetic data were captured using a motion-capture system (Vicon) and two force plates (AMTI). Joint power curves, joint work (positive, negative, absolute) and each joint’s contribution to total lower limb work were analyzed throughout the stance phase using an ANOVA with repeated measures. With increasing inclination positive joint work increased for the ankle and hip joint and in total during uphill walking. Negative joint work increased for each joint and in total work during downhill walking. Absolute work was increased during both uphill (all joints) and downhill (ankle & knee) walking. Knee joint contribution to total negative and absolute work increased during downhill walking while hip and ankle contributions decreased. This study identified, that, when switching from level to a 6° and from 6° to a 12° inclination the gain of individual joint work is more pronounced compared to switching from 12° to an 18° inclination. The results might be used for training recommendations and specific training intervention with respect to sloped walking.     

Discovery of 2,6–difluorobenzyl ether series of phenyl ((R)–3–phenylpyrrolidin–3–yl)sulfones as surprisingly potent,selective and orally bioavailable RORγt inverse agonists

In an effort to discover oral inverse agonists of RORγt to treat inflammatory diseases, a new 2,6–difluorobenzyl ether series of cyclopentyl sulfones were found to be surprisingly more potent than the corresponding alcohol derivatives. When combined with a more optimized phenyl ((R)–3–phenylpyrrolidin–3–yl)sulfone template, the 2,6–difluorobenzyl ethers yielded a set of very potent RORγt inverse agonists (e.g., compound 26, RORγt Gal4 EC₅₀ 11 nM) that are highly selective against PXR, LXRα and LXRβ. After optimizing for stability in human and mouse liver microsomes, compounds 29 and 38 were evaluated in vivo and found to have good oral bioavailability (56% and 101%, respectively) in mice. X–ray co–crystal structure of compound 27 in RORγt revealed that the bulky benzyl ether group causes helix 11 of the protein to partially uncoil to create a new, enlarged binding site, which nicely accommodates the benzyl ether moiety, leading to net potency gain.