Distribution of directional change as a signature of complex dynamics

Analyses of random walks traditionally use the mean square displacement (MSD) as an order parameter characterizing dynamics. We show that the distribution of relative angles of motion between successive time intervals of random walks in two or more dimensions provides information about stochastic processes beyond the MSD. We illustrate the behavior of this measure for common models and apply it to experimental particle tracking data. For a colloidal system, the distribution of relative angles reports sensitively on caging as the density varies. For transport mediated by molecular motors on filament networks in vitro and in vivo, we discover self-similar properties that cannot be described by existing models and discuss possible scenarios that can lead to the elucidated statistical features.Complex dynamics often emerge from ensembles of interacting constituents. Trajectories that are obtained by tracking individual constituents contain information beyond the evolution of ensemble properties, and these data can thus reveal new mechanistic features of the system studied. Examples cut across disciplines and include quantum dots (1), colloidal beads (2), features in cells (3, 4), fish in schools (5), birds in flocks (6), and primates in social groups (7, 8). These data (individual trajectories) demand theoretical frameworks for characterizing and interpreting them.The standard reporter for different forms of motion is the mean square displacement (MSD)where brackets and overlines denote ensemble and time averages, respectively. In simple Brownian motion (9), the MSD grows linearly with the separation in time between two observation points (the lag time, Δ) and does not depend on the amount of data included in averages (the measurement time, T)—i.e., there is ergodicity. Anomalous (i.e., non-Brownian) dynamics can arise from correlations in the walk steps. Correlations in the step sizes [e.g., as in fractional Brownian motion (FBM)] (10) give rise to nonlinear scaling of the MSD with lag time, retaining ergodicity (11). By contrast, a power-law distribution of dwell times [e.g., as in a continuous time random walk (CTRW)] (12) is associated with linear scaling with lag time but nonergodicity (13, 14). The two types of correlations can exist together (4, 15).Despite the success of the MSD as an order parameter for dynamics, it is essentially a 1D measure. We expect random walks in two and more dimensions to contain information beyond the MSD, and various alternative analyses have been suggested (16) (Conclusions). In this paper, we introduce a statistical measure of such information. Specifically, we consider the relative angle, which quantifies the direction of motion over successive time intervals. We show that different models of stochastic processes give rise to different distributions of relative angles and how the intervals can be varied to probe contributing time scales. We apply our order parameter to 2D experimental data obtained for mesoscopic systems. We examine colloidal suspensions at two densities and show that the distribution of relative angles is a sensitive means of detecting and quantifying caging. Two different cytoskeletal systems are considered: insulin-containing vesicles (granules) in a pancreatic cell line (4) and in vitro mixtures of purified myosin motors and actin filaments. These active systems exhibit a common signature of directional motion that cannot be understood in terms of existing models. We propose possible scenarios that could lead to the observed statistics. Together, these examples show that the distribution of relative angles is a straightforward probe of complex dynamics that provides information beyond the MSD.     

脂蛋白a与老年人颈动脉粥样硬化的相关性

目的 :研究脂蛋白 a[L p（a） ]与颈动脉粥样硬化的相关性。方法 :用二维超声显像检测 65例 L p（a）异常和正常的老年人颈动脉结构和血流状态。结果 :L p（a）异常的老年人颈动脉粥样硬化、斑块的发生率及严重程度均明显高于正常组 （P<0 .0 5）。结论 :L p（a）异常与颈动脉粥样硬化相关     

Band-selective gap opening by a C4-symmetric order in a proximity-coupled heterostructure Sr2VO3FeAs

Complex electronic phases in strongly correlated electron systems are manifested by broken symmetries in the low-energy electronic states. Some mysterious phases, however, exhibit intriguing energy gap opening without an apparent signature of symmetry breaking (e.g., high-T_C cuprates and heavy fermion superconductors). Here, we report an unconventional gap opening in a heterostructured, iron-based superconductor Sr₂VO₃FeAs across a phase transition at T₀ ∼150 K. Using angle-resolved photoemission spectroscopy, we identify that a fully isotropic gap opens selectively on one of the Fermi surfaces with finite warping along the interlayer direction. This band selectivity is incompatible with conventional gap opening mechanisms associated with symmetry breaking. These findings, together with the unusual field-dependent magnetoresistance, suggest that the Kondo-type proximity coupling of itinerant Fe electrons to localized V spin plays a role in stabilizing the exotic phase, which may serve as a distinct precursor state for unconventional superconductivity.

Strongly correlated electron systems often exhibit a variety of self-organized forms with broken symmetry. Particularly, in correlated itinerant electron systems, exemplified by doped copper- and iron-based superconductors (FeSCs) (1, 2), multiple many-body instabilities promote rich and complex landscape of electronic orders, including different types of spin, charge, or orbital orders. The resulting broken symmetry renders the footprint in the electronic structure such as band folding, band splitting, and the gap opening. Investigating those footprints thus in turn provides characteristics of phase—what type of phase transition occurs, what kind of interaction is involved, and how the system lowers the energy across the phase transition. For instance, an anisotropic gap opening only at a segment of the Fermi surface (FS) indicates the breaking of translational symmetry and thus suggests a density wave and spin ordering as the corresponding phase (3–5). An isotropic gap opening, on the other hand, can be attributed to a phase without translational symmetry breaking, such as Mott phase. In addition, the loss of coherent spectral weight near the Fermi level could allow us to determine the underlying interaction, such as strong electron correlation (6–9) and coupling with local magnetic moment (10, 11).Recently, in a correlated heterostructure system Sr₂VO₃FeAs, a mysterious phase transition is found to occur at T₀ ∼150 K. The order parameter and thus symmetry of the phase are still elusive, despite the clear thermodynamic evidences for its existence. The system is composed of iron arsenide (SrFeAs) and Mott-insulating transition metal oxide (SrVO₃) layers (Fig. 1 A and B) (12–14). The two constituent layers are known to favor distinct C₂ and C₄ symmetric magnetic phases, respectively. Through a proximity coupling, however, localized spins in the SrVO₃ layers are expected to couple with Fe 3d electrons in the FeAs layers and obtain strong magnetic frustration, which may lead to a transition to a distinct phase. Indeed, recent experimental investigations revealed that the known magnetic phases such as collinear antiferromagnetic (AF) or nematic order of SrFeAs layer and Néel-type AF order in SrVO₃ layer are not stabilized in this system (15). Furthermore, no evidence of time-reversal or lattice symmetry breaking has been observed across this mysterious phase transition (15–17), suggesting an intriguing intraunit cell order with C₄ symmetry.Open in a separate windowFig. 1.Crystal structure of Sr₂VO₃FeAs and the anomalous phase transition. (A and B) The crystal structure of Sr₂VO₃FeAs, a natural heterostructure with [SrFeAs]⁺¹ and [SrVO3]⁻¹ layers. In the [SrVO3]⁻¹ layers, V ions form a network of corner-sharing tetrahedrons, while the FeAs layers consist of edge-sharing FeAs₄ tetrahedrons. The As atoms below the center of the Fe₄ units of the FeAs layer are placed on top of the V atoms in the neighboring SrVO₃ layers, thus bridging the Fe and the V planes as indicated by the dashed lines in B. For clarity, the Sr atoms between these layers are removed in B. (C) The resistivity in the ab plane (ρ_ab) shows a clear anomaly at T₀ ∼150 K, which becomes more clear in its temperature derivative dρ_ab(T)/dT shown in the Inset. With a magnetic field along H ǁ ab or H ǁ c, no shift or broadening is observed in either ρ_ab(T) or dρ_ab(T)/dT curve. The drop in resistivity below 30 K represents the superconducting transition. (D) The specific heat C_p of Sr₂VO₃FeAs as a function of temperature at H = 0, 7, and 14 T. A sharp peak without magnetic field dependence is observed at T₀. The Inset shows C_p(T)/T near the phase transition at T₀.To understand this mysterious phase transition, it is desired to investigate the electronic structure evolution across the transition. Here, via systematic temperature-dependent angle-resolved photoemission spectroscopy (ARPES) studies, we show that the transition accompanies an isotropic gap opening on only one of the FSs with strong interlayer hopping. Our measurements reveal that the lattice C₄ and time-reversal symmetries are retained across the phase transition, which is incompatible with known gap opening mechanisms such as band-selective Mott (6–9) or spin/charge density-wave transitions (3–5). The band selectiveness, which should be from the interlayer hopping strength, together with an unusual magnetoresistance (MR) below T₀ emphasizes the importance of proximity coupling with localized V spins to induce the exotic C₄ symmetric ordered phase. This phase may serve as a distinct parent state for superconductivity in Sr₂VO₃FeAs, in which the usual pairing channel is suppressed by the gap opening.     

Microwave Imaging Sensor Using Compact Metamaterial UWB Antenna with a High Correlation Factor

The design of a compact metamaterial ultra-wideband (UWB) antenna with a goal towards application in microwave imaging systems for detecting unwanted cells in human tissue, such as in cases of breast cancer, heart failure and brain stroke detection is proposed. This proposed UWB antenna is made of four metamaterial unit cells, where each cell is an integration of a modified split ring resonator (SRR), capacitive loaded strip (CLS) and wire, to attain a design layout that simultaneously exhibits both a negative magnetic permeability and a negative electrical permittivity. This design results in an astonishing negative refractive index that enables amplification of the radiated power of this reported antenna, and therefore, high antenna performance. A low-cost FR4 substrate material is used to design and print this reported antenna, and has the following characteristics: thickness of 1.6 mm, relative permeability of one, relative permittivity of 4.60 and loss tangent of 0.02. The overall antenna size is 19.36 mm × 27.72 mm × 1.6 mm where the electrical dimension is 0.20 λ × 0.28 λ × 0.016 λ at the 3.05 GHz lower frequency band. Voltage Standing Wave Ratio (VSWR) measurements have illustrated that this antenna exhibits an impedance bandwidth from 3.05 GHz to more than 15 GHz for VSWR < 2 with an average gain of 4.38 dBi throughout the operating frequency band. The simulations (both HFSS and computer simulation technology (CST)) and the measurements are in high agreement. A high correlation factor and the capability of detecting tumour simulants confirm that this reported UWB antenna can be used as an imaging sensor.     

Conformational changes of calmodulin upon Ca2+ binding studied with a microfluidic mixer

A microfluidic mixer is applied to study the kinetics of calmodulin conformational changes upon Ca2+ binding. The device facilitates rapid, uniform mixing by decoupling hydrodynamic focusing from diffusive mixing and accesses time scales of tens of microseconds. The mixer is used in conjunction with multiphoton microscopy to examine the fast Ca2+-induced transitions of acrylodan-labeled calmodulin. We find that the kinetic rates of the conformational changes in two homologous globular domains differ by more than an order of magnitude. The characteristic time constants are approximately 490 micros for the transitions in the C-terminal domain and approximately 20 ms for those in the N-terminal domain of the protein. We discuss possible mechanisms for the two distinct events and the biological role of the stable intermediate, half-saturated calmodulin.     

Genotype/phenotype correlations of childhood-onset congenital sideroblastic anaemia in a European cohort

Congenital sideroblastic anaemia (CSA) is a rare disease caused by germline mutations of genes involved in haem and iron-sulphur cluster formation, and mitochondrial protein biosynthesis. We performed a retrospective multicentre European study of a cohort of childhood-onset CSA patients to explore genotype/phenotype correlations. We studied 23 females and 20 males with symptoms of CSA. Among the patients, the most frequently mutated genes were ALAS2 (n = 10; 23·3%) and SLC25A38 (n = 8; 18·6%), causing isolated forms of microcytic anaemia of varying severity. Five patients with SLC19A2 mutations suffered from thiamine-responsive megaloblastic anaemia and three exhibited the ‘anaemia, deafness and diabetes’ triad. Three patients with TRNT1 mutations exhibited severe early onset microcytic anaemia associated with thrombocytosis, and two exhibited B-cell immunodeficiency, inflammatory syndrome and psychomotor delay. The prognoses of patients with TRNT1 and SLC2A38 mutations were generally dismal because of comorbidities or severe iron overload. No molecular diagnosis could be established in 14/43 cases. This study emphasizes the frequency of ALAS2 and SLC25A38 mutations and provides the largest comprehensive analysis to date of genotype/phenotype correlations in CSA. Further studies of CSA patients with data recorded in an international registry would be helpful to improve patient management and establish standardized guidelines.     

Complexity of the dynamic QT variability and RR variability in patients with acute anterior wall myocardial infarction: a novel technique using a non-linear method

QT and RR intervals' fluctuations are implicated in the development of malignant arrhythmias. Recent research has quantified repolarization lability using stochastic and linear methods. However, QT-RR intervals are nonlinearly coupled. To this end, QT and RR intervals were extracted from twenty four patients with acute myocardial infarction (AMI) and 13 controls, and a measure of local dimensional complexity (pointwise correlation dimension, PD2) was calculated. PD2 of QT intervals was significantly higher for the patients than for controls (4.83 +/- 0.81 versus 3.40 +/- 0.76, P =.0001), and vice versa for RR intervals (2.51 +/- 0.62 versus 2.91 +/- 0.42, P =.028). The RR and QT measures of complexity were highly correlated only among controls (r = 0.769, P =.0021). Our results support the presence of autonomic abnormalities during infarction and might complement existing tools for assessment of increased risk for sudden death after AMI.     

微小按蚊密度评价灰色模型研究

目的　借助气象、环境与遥感监测指标建立微小按蚊密度评价模型。　方法　以云南省10县27乡为研究现场,收集1984～1993年各乡气象、环境、遥感与蚊媒监测资料。对18项指标与微小按蚊密度的关系进行灰色关联度分析,按照灰色阈值筛选评价指标,合成变量E,研究变量E与微小按蚊密度的关系,从而建立微小按蚊密度评价灰色模型。　结果　以0.70灰色阈值筛选微小按蚊密度评价指标并排列灰色关联序:干季月平均温度>干季最低温度>湿季最低温度>湿季归一化植被指数(NDVI)>湿季月平均温度>水田面积占耕地面积的比例>干季月最高温度>湿季月最高温度。微小按蚊密度灰色评价模型为:y=0.0578e0·0780(8X10'+7X12'+6X11'+5X15'+4X9'+3X4'+2X8'+1X7')模型判定的正确率为92.0%, e0.5=18%,最大相对误差为-15%,最小相对误差为4%,平均相对误差为21%。结论 借助微小按蚊密度评价模型可以对疟疾疫点微小按蚊密度进行拟合评价。     

半乳糖凝集素1与动脉粥样硬化风险之间的因果关联:一项两样本孟德尔随机化研究

目的]探讨遗传预测的半乳糖凝集素1(Gal-1)水平与动脉粥样硬化(As)之间的因果关联。 [方法]采用两样本孟德尔随机化(MR)研究方法,选择与Gal-1相关联的单核苷酸多态性(SNP)位点作为工具变量(IV),评估遗传预测的循环Gal-1水平与不同部位As风险的因果关联。 [结果]逆方差加权法(IVW)分析结果显示,经过Bonferroni校正后遗传预测的循环Gal-1水平与外周动脉粥样硬化及其他部位动脉粥样硬化(除外脑动脉、冠状动脉及外周动脉)的风险呈正相关(OR=1.6,5%CI:1.05～1.27,P＝0.002;OR=1.16,95%CI:1.12～1.20,P＝4.11E－17),而与冠状动脉粥样硬化和脑动脉粥样硬化发生风险均未发现存在因果关联的证据(OR=1.02,95%CI:0.91～1.14,P＝0.765;OR=1.10,95%CI:0.94～1.29,P＝0.220);在应用荟萃分析合并上述不同部位As的效应值后,遗传预测的循环Gal-1水平与As风险呈正相关(OR=1.12,95%CI:1.06～1.19)。 [结论]遗传预测的循环Gal-1水平与As的发病风险存在因果关联,Gal-1是预防As发生的潜在靶点。     

Surface-coupled proton exchange of a membrane-bound proton acceptor

Proton-transfer reactions across and at the surface of biological membranes are central for maintaining the transmembrane proton electrochemical gradients involved in cellular energy conversion. In this study, fluorescence correlation spectroscopy was used to measure the local protonation and deprotonation rates of single pH-sensitive fluorophores conjugated to liposome membranes, and the dependence of these rates on lipid composition and ion concentration. Measurements of proton exchange rates over a wide proton concentration range, using two different pH-sensitive fluorophores with different pK_as, revealed two distinct proton exchange regimes. At high pH (> 8), proton association increases rapidly with increasing proton concentrations, presumably because the whole membrane acts as a proton-collecting antenna for the fluorophore. In contrast, at low pH (< 7), the increase in the proton association rate is slower and comparable to that of direct protonation of the fluorophore from the bulk solution. In the latter case, the proton exchange rates of the two fluorophores are indistinguishable, indicating that their protonation rates are determined by the local membrane environment. Measurements on membranes of different surface charge and at different ion concentrations made it possible to determine surface potentials, as well as the distance between the surface and the fluorophore. The results from this study define the conditions under which biological membranes can act as proton-collecting antennae and provide fundamental information on the relation between the membrane surface charge density and the local proton exchange kinetics.     

Anisotropic Mechanical Response and Strain Localization of a Metallic Glassy-Fiber-Reinforced Polyethylene Terephthalate Fabric

Optimizing the mechanical properties of composites through microstructural design has been a long-standing issue in materials science. In this study, we reinforced a typical polymer, i.e., polyethylene-terephthalate-woven fabric, with a type of Fe-based metallic glassy fiber (MGF) with an extremely large Young’s moduli. The MGF-reinforced fabrics, with three different fiber bundle orientations (0°, 45°, and 90°), were investigated by in situ electron-microscopy mechanical testing techniques in conjunction with a digital image correlation (DIC) technique. The fabrics exhibited a pronounced anisotropic mechanical response, and the associated characteristics were verified to depend on the fiber bundle orientation relative to the external load. Furthermore, localized strains near the intersections of the fiber bundles were found to be much higher than the global strain. It is confirmed that the restriction from warp to weft is the dominant factor influencing strain localization during deformation. Our results are enlightening for understanding the fracture mechanisms of composites.     

Diabetic Foot Disease: Emerging Technologies: Validation of Plantar Pressure Measurements for a Novel In-Shoe Plantar Sensory Replacement Unit

Background

Research concerning prevention of diabetic foot complications is critical. A novel in-shoe plantar sensory replacement unit (PSRU) has been developed that provides alert-based feedback derived from analyzing plantar pressure threshold measurements in real time. The purpose of this study was to compare the PSRU device to a gold standard pressure-sensing device (GS-PSD) to determine the correlation between concurrent measures of plantar pressure during walking.

Methods

The PSRU had an array of eight sensors with a range of 10–75 mm Hg and collected data at 4 Hz, whereas the GS-PSD had 99 sensors with a range of 1–112 mm Hg and collected data at 100 Hz. Based on an a priori power analysis, data were collected from 10 participants (3 female, 7 male) while walking over ground in both devices. The primary variable of interest was the number of data points recorded that were greater than 32 mm Hg (capillary arterial pressure—the minimum pressure reported to cause pressure ulcers) for each of the eight PSRU sensors and corresponding average recordings from the GS-PSD sensor clusters. Intraclass correlation coefficient (2,1) was used to compare data between the two devices.

Results

Compared with the GS-PSD, we found good-to-very-good correlations (r-value range 0.67–0.86; p-value range 0.01–0.05) for six of the PSRU’s eight sensors and poor correlation for only two sensors (r = 0.41, p = .15; r = 0.38, p = .18) when measuring the number of data points recorded that were greater than 32 mm Hg.

Conclusions

Based on the results of the present study, we conclude the PSRU provides analogous data when compared with a GS-PSD.     

藐小棘隙吸虫感染与其它寄生虫感染关系及化疗效果

五年研究发现,人群藐小棘隙吸虫感染率与蛔虫感染率明显相关,推测年龄趋向性行为系共同的易感因素;同时化疗后,与钩虫感染率明显负相关性及与鞭虫感染率明显相关性基本消失,与血吸虫感染率几无相关,可能因不同的感染方式、途径,及较低的感染率所致。吡喹酮治疗对人群藐小棘隙吸虫感染率下降效果显著。     

From the Cover: High-throughput sequencing reveals inbreeding depression in a natural population

Proxy measures of genome-wide heterozygosity based on approximately 10 microsatellites have been used to uncover heterozygosity fitness correlations (HFCs) for a wealth of important fitness traits in natural populations. However, effect sizes are typically very small and the underlying mechanisms remain contentious, as a handful of markers usually provides little power to detect inbreeding. We therefore used restriction site associated DNA (RAD) sequencing to accurately estimate genome-wide heterozygosity, an approach transferrable to any organism. As a proof of concept, we first RAD sequenced oldfield mice (Peromyscus polionotus) from a known pedigree, finding strong concordance between the inbreeding coefficient and heterozygosity measured at 13,198 single-nucleotide polymorphisms (SNPs). When applied to a natural population of harbor seals (Phoca vitulina), a weak HFC for parasite infection based on 27 microsatellites strengthened considerably with 14,585 SNPs, the deviance explained by heterozygosity increasing almost fivefold to a remarkable 49%. These findings arguably provide the strongest evidence to date of an HFC being due to inbreeding depression in a natural population lacking a pedigree. They also suggest that under some circumstances heterozygosity may explain far more variation in fitness than previously envisaged.It has long been known that inbreeding can reduce fitness, mainly through the unmasking of recessive or partially recessive deleterious alleles (1). Such effects are well documented in the laboratory (2, 3) but until recently have remained largely unstudied in natural populations (4, 5). This is because an individual’s inbreeding coefficient (f) can be calculated directly only by using a deep pedigree, and these pedigrees are seldom available outside the laboratory (6). However, because inbreeding increases an individual’s homozygosity, the heterozygosity of a panel of neutral genetic markers can in theory be used as a surrogate for f.Initial searches for heterozygosity fitness correlations (HFCs) (7, 8) used allozymes, but the results obtained are difficult to interpret because the proteins themselves may be under selection. With the discovery of microsatellites, an abundant class of putatively neutral genetic marker, it became possible to look for HFCs without concerns about selection on the markers themselves. A burgeoning literature now shows that HFCs based on small numbers of microsatellite loci are found in many bird and mammal species for a remarkable range of fitness traits, including neonatal survival (9), parasite susceptibility (10) and lifetime reproductive success (11), and even behavioral qualities such as territory-holding ability (12), song complexity (13) and attractiveness (14). This weight of evidence suggests that HFCs are an important and widespread phenomenon in the natural world. It is therefore important to understand their basis.Theory predicts that HFCs arise as a result of inbreeding depression, which will reduce the fitness of individuals in proportion to their inbreeding coefficient f (7). Therefore, variance in inbreeding coefficients within a population is necessary to generate HFCs. However, simulation and empirical studies indicate that the variance in f in natural populations is usually low, and estimates of f based on the small numbers of markers typically deployed are often very poor (15). As a result, HFCs will usually be weak or nonsignificant even when inbreeding actually explains a large proportion of fitness. Szulkin et al. (16) summarized this by saying that HFCs allow one to see only the “tip of the iceberg” and provided two examples in which heterozygosity explains 3% and 6% of trait variation even though inbreeding is expected to account for 24% and 30% of the variance, respectively. The most favorable situations to observe HFCs are in populations where inbred individuals are not rare due to factors such as small population size, extreme reproductive skew, and natal philopatry (15), but even in these cases using only a few markers severely curtails the power to observe the actual impact of inbreeding.To explain HFCs, authors also frequently invoke “local effects” where one or a small number of the microsatellites used as markers are by chance linked to a gene experiencing heterozygote advantage (8). Local effects are widely discussed in the literature, but their importance is unclear given that balanced polymorphisms are thought to be rare (17) and strong linkage between random pairs of loci is infrequent (16). It has also been argued that the contribution of local effects to HFCs may be overstated due to many studies having used an inappropriate statistical framework (16).One means of unambiguously testing whether inbreeding alone can explain HFCs is to deploy a larger number of genetic markers (18). If an HFC is due to inbreeding depression, the use of more markers will reduce the error variance in the estimation of genome-wide heterozygosity and thereby strengthen the correlation. In contrast, if the HFC is highly dependent on one or a few marker loci being by chance linked to a fitness locus with strong effects, as in the local effect model, adding more markers located throughout the genome will reduce the strength of the HFC as the contribution of any one marker becomes progressively diluted. Until recently, however, this approach was not available to most studies because of the prohibitive costs of developing and screening large numbers of additional microsatellites.Restriction site associated DNA (RAD) sequencing (19) has recently emerged as a rapid and economic means of genotyping thousands of single nucleotide polymorphisms (SNPs) in virtually any organism. This approach concentrates high-throughput sequencing effort around restriction enzyme cut sites that are distributed across the genome, thereby generating sufficiently deep local sequence coverage to reliably call SNPs as being either heterozygous or homozygous. Although SNPs are individually less informative than microsatellites due to their lower allelic diversity, this should be more than compensated for by the large numbers of markers screened, in principle allowing genome-wide heterozygosity to be estimated with far greater precision than previously possible.Here, we evaluated the ability of RAD sequencing to accurately estimate genome-wide heterozygosity using an experimental population of oldfield mice (Peromyscus polionotus subgriseus) with known pedigree-based inbreeding coefficients (20). We then applied RAD sequencing to a natural population of harbor seals (Phoca vitulina) to determine whether inbreeding explains previously reported HFCs for survivorship and parasite infection (21). We hypothesized that these HFCs should strengthen with the deployment of many thousands of SNPs if they are due to inbreeding.     

Full-Field Measurements in the Edge Crush Test of a Corrugated Board—Analytical and Numerical Predictive Models

This article focuses on the derivation of simplified predictive models for the identification of the overall compressive stiffness and strength of corrugated cardboards. As a representative example an unsymmetrical 5-ply sample (with E and B flute) was used in this study. In order to exclude unreliable displacement measurement in the standard edge crush test, virtual strain gauges were used. Video extensometry was employed to collect measurements from the outer surfaces of the sample on both sides. Additional data allowed real force-displacement curves to be obtained, which were used in the validation procedure. To emulate the experimental results, besides a simple analytical model, a 3D numerical model fully reflecting the geometry of the corrugated board, based on the finite elements method was also built. In both cases good agreement between the experimental results and the analytical and numerical calculations was observed. This proved that the proposed analytical model can be successfully used to determine the overall stiffness and compressive strength of corrugated board, provided that the geometry and properties of all the layers of the board are known. The simple model presented in this work enables quick and reliable design and prototyping of new assemblies without the need to manufacture them.     

Multi‐institutional randomized control study of haemolysis in stored red cell units prepared manually or by an automated system

Background The haemolysis level at the end of storage is a performance parameter for RBC preparations. In the evaluation of new devices or new processes for processing blood, it is relevant to evaluate whether the haemolysis is linked to (1) specific characteristics of the blood donor, or (2) the nature of the blood‐processing methodologies. Materials and Methods As part of the validation of a new automated whole blood processing system compared to the current manual methods, randomized, paired crossover studies were conducted evaluating measures of blood component quality, including RBC haemolysis over 42 days of storage. Results The association between haemolysis and the individual subject was evaluated by modelling haemolysis with independent predictors of treatment (control and test processing) and leucocyte reduction as fixed factors with donor and laboratory as random effects in a mixed‐effects anova model. It was found that the day 42 haemolysis values were strongly dependent on the donor subject, with an intraclass correlation coefficient of 0·81. Conclusions The data reported in this study suggest a link between the specific whole blood donor and the haemolysis levels observed in red‐blood‐cell units stored refrigerated for 42 days. Additional research to identify possible donor characteristics associated with haemolysis during storage is warranted.     

Brain palpation from physiological vibrations using MRI

We present a magnetic resonance elastography approach for tissue characterization that is inspired by seismic noise correlation and time reversal. The idea consists of extracting the elasticity from the natural shear waves in living tissues that are caused by cardiac motion, blood pulsatility, and any muscle activity. In contrast to other magnetic resonance elastography techniques, this noise-based approach is, thus, passive and broadband and does not need any synchronization with sources. The experimental demonstration is conducted in a calibrated phantom and in vivo in the brain of two healthy volunteers. Potential applications of this “brain palpation” approach for characterizing brain anomalies and diseases are foreseen.The complexity of wave fields can sometimes be an advantage for imaging. Such is the case in multiple scattering or reverberating media, where wave fields contain information about their sources and the medium itself. Turning this wave noise into useful measurements through correlation techniques has provided a breakthrough in a wide variety of domains, which range from seismology (1) to acoustics (2, 3) and electromagnetism (4). Living tissue is also full of unexploited vibrations. Their detection with ultrafast ultrasound scanners that can reach thousands of frames per second (5–7) has recently opened up the medical field to correlation techniques and therefore, passive elastography (8). However, ultrasound is not suitable for brain imaging. MRI can image the brain, but its relatively low acquisition rate of a few frames per second is an issue. Synchronization with the shear-wave source is, thus, necessary (9, 10), which penalizes its potential implementation based on natural shear waves.We describe a magnetic resonance elastography (MRE) -based method that is free from the need for synchronization and any controlled source. This approach extracts information related to the mechanical properties of the soft tissue from hundreds of snapshots of randomly fluctuating shear-wave fields. The key to decrypting the complex field is correlation or similarly but from a physical point of view, time reversal (11, 12). Not only does this wide-band approach maximize the signal-to-noise ratio, as any matched filter would, but it also avoids the Nyquist–Shannon problem that is inherent to slow imaging devices. Indeed, although time information is definitely lost, the spatial information is still present and allows shear-wavelength tomography to be conducted. This wavelength is closely related to the shear elasticity and thus, the intuitive estimation of the stiffness felt by physicians during palpation examination. To start, this concept is shown using MRI in a calibrated elastography phantom under randomly sampled vibrations. Arterial pulsation can produce motion in the brain as high as 1 mm (13); the resulting natural shear-wave field is analyzed through correlation algorithms, and passive brain palpation reconstructions are presented.