Search

• Acute social defeat alters morphology of microglia in infralimbic cortex. • Dominant hamsters show less reactive microglia and cell damage than subordinates. • Blocking microglia activity with minocycline increased stress-related behavior. • Microglia activity in the infralimbic cortex may be necessary for stress coping. Chronic stress increases activity of the brain's innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner. We found that acute social defeat increased expression of ionized calcium binding adapter molecule 1 (Iba1) in the infralimbic (IL) and prelimbic (PL) and altered the morphology Iba1+ cells 1, 2, and 7 days after social defeat. We also investigated whether acute defeat induced tissue degeneration and reductions of synaptic plasticity 2 days post-defeat. We found that while social defeat increased deposition of cellular debris and reduced synaptophysin immunoreactivity in the PL and IL, treatment with minocycline protected against these cellular changes. Finally, we tested whether a reduced conditioned defeat response in dominant compared to subordinate hamsters was associated with changes in microglia reactivity in the IL and PL. We found that while subordinate hamsters and those without an established dominance relationships showed defeat-induced changes in morphology of Iba1+ cells and cellular degeneration, dominant hamsters showed resistance to these effects of social defeat. Taken together, these findings indicate that acute social defeat alters microglial morphology, increases markers of tissue degradation, and impairs structural integrity in the IL and PL, and that experience winning competitive interactions can specifically protect the IL and reduce stress vulnerability. [ABSTRACT FROM AUTHOR]

Modal analysis techniques are widely used to characterize vibrations in structures, vehicles, machinery, etc. Modal parameters obtained through modal analysis are useful for structural health monitoring and condition monitoring. The common goal is to ensure the integrity of a mechanical system through monitoring of different operational conditions. Operational conditions described by spatial measurements can for instance be used to observe the vibration characteristics of the system and its parts. Therefore, the main originality of this work is to experimentally investigate if the presence of a turbulent gas flow in seal geometries can facilitate operational modal analysis for a coupled rotor–foundation system. A consistent and automatic way of obtaining the vibration characteristics is necessary to be included in the monitoring schemes. Therefore, this work also proposes a method to automatically obtain modal parameters for a bed plate of a rotor–foundation system when the rotor is affected by active magnetic bearings and gas seals. The automatic modal parameter algorithm is built on the stabilization diagram of modal parameters obtained from the stochastic subspace identification. Intermediate results from the automatic modal parameter algorithm show that some of the distance measures i.e., d ω n , d , d ζ , dMACX, d λ , d MACX ω n , d , d MACX ζ , and d MACX λ , for modal parameters in a stabilization diagram are better suited than others when distinguishing between possible physical modes and certainly spurious poles. The frequency band of interest for the system is found to influence the number of possible physical modes identified by the automatic algorithm. Measurements from 13 roving accelerometers are combined with the automatic modal parameter algorithm to obtain the vibration characteristics of the rotor and bed plate. For different operational conditions in the seal geometry, seven modes are consistently identified as physical modes by the automatic modal parameter algorithm. The algorithm uses (i) a combination of a white noise disturbance pattern intentionally introduced into the system through the active magnetic bearings and (ii) the operational disturbance coming from the seals, non-intentionally introduced by the turbulent gas flow. The seven physical modes are also identified when (iii) the rotor–foundation system is only disturbed from the turbulent gas flow in the seals. The seven physical modes identified by the algorithm under conditions (i), (ii), and (iii) compare well to the vibration characteristics found in experiments via experimental modal analysis and impact hammer testing as well as via a mathematical model of the rotor–foundation system. [ABSTRACT FROM AUTHOR]

Recently, our laboratory had produced five families of transgenic rainbow trout harboring cecropin P1 transgene, and via repeated challenge studies these fish exhibited a significant elevation of resistance to infection by microbial pathogens. By cDNA microarray and mRNA deep sequencing (mRNA-seq) analyses on two of the five families of cecropin P1 transgenic fish, differentially expressed genes (DEGs) relevant to the innate and adaptive immune pathways in three different immune-related tissues, (i.e. spleen, kidney and liver) were profiled. These results supported our hypothesis that in addition to its direct microbicidal activity, the transgene product of cecropin P1 induces immunomodulatory activity in the transgenic host. Here, we have adapted the technique of quantitative reverse transcription real time PCR (RT-qPCR) array to analyze the expression of genes relevant to the innate and adaptive immune pathways in the rest three families. A RT-qPCR array was constructed with oligonucleotide primers of fifty-two innate/adaptive immune relevant DEGs shown to be the most perturbed by cecropin P1 transgene product in previous studies. Messenger RNA isolated from the spleen, kidney and liver of transgenic fish and non-transgenic fish control were studied on this array. Results of RT-qPCR array revealed that statistically significant perturbations of gene expression were detected in pathways of cytokine/chemokine signaling, Toll-like receptor signaling, complement cascade, antigen processing/presentation, lysosomal phagocytosis and leukocyte trans-endothelial migration in the transgenic spleen; extracellular matrix (ECM) organization and leukocyte trans-endothelial migration pathways in the transgenic kidney; lysosomal activity pathway in the transgenic liver. Furthermore, genes related to the pathways of the peroxisome proliferator-activated receptors (PPAR) signaling, lipid metabolism process and arachidonic acid metabolism were also impacted in the transgenic liver. Findings of the current study are in good agreement with those discoveries in previous two transgenic families by cDNA microarray and mRNA-seq analyses. • Cecropin P1 transgene product modulates the innate/adaptive immunity in the transgenic rainbow trout. • Transgenic spleen exhibited functional perturbations in a broad-range of immune relevant pathways. • Transgenic kidney exerted suppressions in leukocyte trans-endothelial migration and ECM organization. • Transgenic liver wielded functional disturbance in the immune pathway of lysosomal phagocytosis and alterations to energy efficiency related processes. • Custom-made RT-qPCR array provides a new, fast, and lower in cost screening method to select and breed high disease resistant strains of marine species. [ABSTRACT FROM AUTHOR]

There is no comprehensive storage for generated mutants of Fusarium graminearum or data associated with these mutants. Instead, researchers relied on several independent and non-integrated databases. FgMutantDb was designed as a simple spreadsheet that is accessible globally on the web that will function as a centralized source of information on F. graminearum mutants. FgMutantDb aids in the maintenance and sharing of mutants within a research community. It will serve also as a platform for disseminating prepublication results as well as negative results that often go unreported. Additionally, the highly curated information on mutants in FgMutantDb will be shared with other databases (FungiDB, Ensembl, PhytoPath, and PHI-base) through updating reports. Here we describe the creation and potential usefulness of FgMutantDb to the F. graminearum research community, and provide a tutorial on its use. This type of database could be easily emulated for other fungal species. [ABSTRACT FROM AUTHOR]

E-peptide of the pro-Insulin-like growth factor-I (pro-IGF-I) is produced from pre-pro-IGF-I by proteolytic cleavage in the post-translational processing. The human Eb-peptide (hEb-peptide), derived from the E domain of pro-IGF-IB isoform, is a bioactive molecule whose exact physiological role remains elusive. Accumulated evidence reported from our laboratory indicated that hEb-peptide possesses activity against multiple hallmark characteristics of solid tumor in different cancer cell types. In human breast carcinoma cells (MDA-MB-231), it was demonstrated that hEb-peptide can promote cell attachment to substratum, inhibit colony formation in a semisolid medium, reduce cancer cell invasion, and inhibit cancer-induced angiogenesis. Like the action of other peptide hormones, these cellular responses triggered by hEb may be initiated through binding to a receptor molecule residing on the surface of the cell. Our laboratory and the others have previously provided evidence demonstrating the existence of hEb-peptide specific binding components residing on the cell membrane. In this study, we report the isolation and identification of eight protein molecules bound reversibly with hEb-peptide from the membrane preparation of MDA-MB-231 cells. Some of the identified proteins are known to be present at cell surface and function as receptors while the others are not. The functions of these molecules reveal strong correlation with the demonstrated activities of hEb-peptide on MDA-MB-231cells, suggesting hEb-peptide activity on cancer cells might be mediated by these molecules. [ABSTRACT FROM AUTHOR]

The ability to discriminate signal from noise plays a key role in the analysis and interpretation of functional magnetic resonance imaging (fMRI) measures of brain activity. Over the past two decades, a number of major sources of noise have been identified, including system-related instabilities, subject motion, and physiological fluctuations. This article reviews the characteristics of the various noise sources as well as the mechanisms through which they affect the fMRI signal. Approaches for distinguishing signal from noise and the associated challenges are also reviewed. These challenges reflect the fact that some noise sources, such as respiratory activity, are generated by the same underlying brain networks that give rise to functional signals that are of interest. [ABSTRACT FROM AUTHOR]

The global signal is widely used as a regressor or normalization factor for removing the effects of global variations in the analysis of functional magnetic resonance imaging (fMRI) studies. However, there is considerable controversy over its use because of the potential bias that can be introduced when it is applied to the analysis of both task-related and resting-state fMRI studies. In this paper we take a closer look at the global signal, examining in detail the various sources that can contribute to the signal. For the most part, the global signal has been treated as a nuisance term, but there is growing evidence that it may also contain valuable information. We also examine the various ways that the global signal has been used in the analysis of fMRI data, including global signal regression, global signal subtraction, and global signal normalization. Furthermore, we describe new ways for understanding the effects of global signal regression and its relation to the other approaches. [ABSTRACT FROM AUTHOR]

Objective: Design and implement a HIPAA and Integrating the Healthcare Enterprise (IHE) profile compliant automated pipeline, the integrated Genomics Anesthesia System (iGAS), linking genomic data from the Mount Sinai Health System (MSHS) BioMe biobank to electronic anesthesia records, including physiological data collected during the perioperative period. The resulting repository of multi-dimensional data can be used for precision medicine analysis of physiological readouts, acute medical conditions, and adverse events that can occur during surgery.Materials and Methods: A structured pipeline was developed atop our existing anesthesia data warehouse using open-source tools. The pipeline is automated using scheduled tasks. The pipeline runs weekly, and finds and identifies all new and existing anesthetic records for BioMe participants.Results: The pipeline went live in June 2015 with 49.2% (n=15,673) of BioMe participants linked to 40,947 anesthetics. The pipeline runs weekly in minimal time. After eighteen months, an additional 3671 participants were enrolled in BioMe and the number of matched anesthetic records grew 21% to 49,545. Overall percentage of BioMe patients with anesthetics remained similar at 51.1% (n=18,128). Seven patients opted out during this time. The median number of anesthetics per participant was 2 (range 1-144). Collectively, there were over 35 million physiologic data points and 480,000 medication administrations linked to genomic data. To date, two projects are using the pipeline at MSHS.Conclusion: Automated integration of biobank and anesthetic data sources is feasible and practical. This integration enables large-scale genomic analyses that might inform variable physiological response to anesthetic and surgical stress, and examine genetic factors underlying adverse outcomes during and after surgery. [ABSTRACT FROM AUTHOR]

Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) enables a wide array of studies, from measuring the strength of a ligand–receptor bond to elucidating the complex folding pathway of individual membrane proteins. Such SMFS studies and, more generally, the diverse applications of AFM across biophysics and nanotechnology are improved by enhancing data quality via improved force stability, force precision, and temporal resolution. For an advanced, small-format commercial AFM, we illustrate how these three metrics are limited by the cantilever itself rather than the larger microscope structure, and then describe three increasingly sophisticated cantilever modifications that yield enhanced data quality. First, sub-pN force precision and stability over a broad bandwidth (Δ f = 0.01–20 Hz) is routinely achieved by removing a long ( L = 100 μm) cantilever’s gold coating. Next, this sub-pN bandwidth is extended by a factor of ∼50 to span five decades of bandwidth (Δ f = 0.01–1000 Hz) by using a focused ion beam (FIB) to modify a shorter ( L = 40 μm) cantilever. Finally, FIB-modifying an ultrashort ( L = 9 μm) cantilever improves its force stability and precision while maintaining 1-μs temporal resolution. These modified ultrashort cantilevers have a reduced quality factor ( Q ≈ 0.5) and therefore do not apply a substantial (30–90 pN), high-frequency force modulation to the molecule, a phenomenon that is unaccounted for in traditional SMFS analysis. Currently, there is no perfect cantilever for all applications. Optimizing AFM-based SMFS requires understanding the tradeoffs inherent to using a specific cantilever and choosing the one best suited to a particular application. [ABSTRACT FROM AUTHOR]

Rotor dynamic force coefficients of gas seals strongly depend on the machine operational conditions. These force coefficients influence the overall dynamical response and modal properties of machines, consequently defining the machine vibration levels. Accurate estimations of the rotor dynamic coefficients are required for designing machines with low vibration amplifications and well-defined stability margins throughout the operational range. Experimental methods applied to test benches are used to validate such force coefficients and they normally rely on (i) the quality of the measurements and (ii) the assumption that the mathematical model is able to capture the whole system dynamics. If relevant dynamical contributions in a system are neglected by the mathematical model, the contribution will erroneously be concluded to originate from the seal being tested. The theoretical and experimental investigation in this paper focuses on quantifying and qualifying the effect of neglected system dynamics modelling on the estimation of seals force coefficients and stability margins. The in-situ identification of seal forces shows that the direct stiffness, cross-coupling stiffness, and direct damping coefficient estimations for a gas seal with high preswirl are statistically significantly affected by the baseline model. Nevertheless, the baseline model leads to small deviations of the seal force coefficient estimations. The prediction accuracy of stability margins is found to be more influenced by the baseline model describing the system dynamics than by the deviations between the seal force coefficient estimations. [ABSTRACT FROM AUTHOR]

The ability to discriminate signal from noise plays a key role in the analysis and interpretation of functional magnetic resonance imaging (fMRI) measures of brain activity. Over the past two decades, a number of major sources of noise have been identified, including system-related instabilities, subject motion, and physiological fluctuations. This article reviews the characteristics of the various noise sources as well as the mechanisms through which they affect the fMRI signal. Approaches for distinguishing signal from noise and the associated challenges are also reviewed. These challenges reflect the fact that some noise sources, such as respiratory activity, are generated by the same underlying brain networks that give rise to functional signals that are of interest. [ABSTRACT FROM AUTHOR]

• Rigorous analysis of temporal SNR (tSNR) and differential CNR (dCNR) for multi-echo fMRI. • A geometric view provides insight into the variation of tSNR and dCNR across multi-echo weight combinations. • There are three major regimes of performance: tSNR robust, dCNR robust, and within-type robust. In multi-echo fMRI (ME-fMRI), two metrics have been widely used to measure the performance of various acquisition and analysis approaches. These are temporal SNR (tSNR) and differential contrast-to-noise ratio (dCNR). A key step in ME-fMRI is the weighted combination of the data from multiple echoes, and prior work has examined the dependence of tSNR and dCNR on the choice of weights. However, most studies have focused on only one of these two metrics, and the relationship between the two metrics has not been examined. In this work, we present a geometric view that offers greater insight into the relation between the two metrics and their weight dependence. We identify three major regimes: (1) a tSNR robust regime in which tSNR is robust to the weight selection with most weight variants achieving close to optimal performance, whereas dCNR shows a pronounced dependence on the weights with most variants achieving suboptimal performance; (2) a dCNR robust regime in which dCNR is robust to the weight selection with most weight variants achieving close to optimal performance, while tSNR exhibits a strong dependence on the weights with most variants achieving significantly lower than optimal performance; and (3) a within-type robust regime in which both tSNR and dCNR achieve nearly optimal performance when the form of the weights are variants of their respective optimal weights and exhibit a moderate decrease in performance for other weight variants. Insight into the behavior observed in the different regimes is gained by considering spherical representations of the weight dependence of the components used to form each metric. For multi-echo acquisitions, dCNR is shown to be more directly related than tSNR to measures of CNR and signal-to-noise ratio (SNR) for task-based and resting-state fMRI scans, respectively. [ABSTRACT FROM AUTHOR]

Abstract: There has been growing interest in the use of resting-state functional magnetic resonance imaging (rsfMRI) for the assessment of disease and treatment, and a number of studies have reported significant disease-related changes in resting-state blood oxygenation level dependent (BOLD) signal amplitude and functional connectivity. rsfMRI is particularly suitable for clinical applications because the approach does not require the patient to perform a task and scans can be obtained in a relatively short amount of time. However, the mechanisms underlying resting-state BOLD activity are not well understood and thus the interpretation of changes in resting state activity is not always straightforward. The BOLD signal represents the hemodynamic response to neural activity, and changes in resting-state activity can reflect a complex combination of neural, vascular, and metabolic factors. This paper examines the role of neurovascular factors in rsfMRI and reviews approaches for the interpretation and analysis of resting state measures in the presence of confounding factors. [Copyright &y& Elsevier]

Abstract: Recent epidemiological evidence in children indicates that time spent outdoors is protective against myopia. Studies in animal models (chick, macaque, tree shrew) have found that light levels (similar to being in the shade outdoors) that are mildly elevated compared to indoor levels, slow form-deprivation myopia and (in chick and tree shrew) lens-induced myopia. Normal chicks raised in low light levels (50 lux) with a circadian light on/off cycle often develop spontaneous myopia. We propose a model in which the ambient illuminance levels produce a continuum of effects on normal refractive development and the response to myopiagenic stimuli such that low light levels favor myopia development and elevated levels are protective. Among possible mechanisms, elevation of retinal dopamine activity seems the most likely. Inputs from intrinsically-photosensitive retinal ganglion cells (ipRGCs) at elevated light levels may be involved, providing additional activation of retinal dopaminergic pathways. [Copyright &y& Elsevier]

Abstract: The diversity of experimental designs that can be used with functional magnetic resonance imaging (fMRI) has played a key role in its widespread application to studies of human cognition. This flexibility is possible because the fMRI response to external stimuli is remarkably well approximated as the response of a linear time variant system. The experimental demonstration of this property provided the foundation for the development of event-related designs, in which the fMRI response is modeled as the linear summation of the hemodynamic response to discrete events. Building upon prior work from the fields of engineering, neuroscience, and statistics, researchers in the field have created a rich collection of event-related designs and developed a rigorous theoretical framework for characterizing and optimizing the performance of designs. Ongoing challenges include the optimization of designs in the presence of experimental constraints and the development of more time-efficient optimization algorithms. [Copyright &y& Elsevier]

Abstract: Correlations between spontaneous fluctuations in the blood oxygenation level dependent (BOLD) signal measured with functional MRI are finding increasing use as measures of functional connectivity in the brain, where differences can potentially predict cognitive performance and diagnose disease. Caffeine, which is a widely consumed neural stimulant and vasoactive agent, has been found to decrease the amplitude and correlation of resting-state BOLD fluctuations, and hence is an important factor to consider in functional connectivity studies. However, because the BOLD signal is sensitive to neural and vascular factors, the physiological mechanisms by which caffeine alters spontaneous BOLD fluctuations remain unclear. Resting-state functional connectivity has traditionally been assessed using stationary measures, such as the correlation coefficient between BOLD signals measured across the length of a scan. However, recent work has shown that the correlation of resting-state networks can vary considerably over time, with periods as short as 10s. In this study, we used a sliding window correlation analysis to assess temporal variations in resting-state functional connectivity of the motor cortex before and after caffeine ingestion. We found that the temporal variability of BOLD correlation was significantly higher following a caffeine dose, with transient periods of strong correlation alternating with periods of low or negative correlation. This phenomenon was primarily due to increased variability in the phase difference between BOLD time courses in the left and right motor cortices. These results indicate that caffeine may cause underlying spontaneous neural fluctuations to go in and out of coherence more frequently, and emphasizes the need to consider non-stationary measures when studying changes in functional connectivity. [Copyright &y& Elsevier]

Abstract: Resting-state functional magnetic resonance imaging (fMRI) is proving to be an effective tool for mapping the long-range functional connections of the brain in both health and disease. One of the primary measures of connectivity is the correlation between the blood oxygenation level dependent (BOLD) time series observed in different brain regions. The computation of the correlation is often dominated by the presence of a strong global component that can introduce significant variability across functional connectivity maps acquired from different experimental scans or subjects. To address this issue, a variety of global signal correction methods have been proposed, but there is currently a lack of a clear consensus on the best approach to use. Furthermore, there has been concern that some global signal correction methods, such as global signal regression, may produce significant negative bias in the correlation values. In this paper we introduce a framework for visualizing the signal structure of resting-state fMRI data and characterizing the properties of the global signal. Using this framework, we demonstrate that a portion of the global signal can be viewed as an additive confound that increases with the mean BOLD amplitude. An approach for minimizing the contribution of this additive confound is presented, and an initial comparison with existing global signal correction methods is provided. [Copyright &y& Elsevier]

Abstract: We examined normal emmetropization and the refractive responses to binocular plus or minus lenses in young (late infantile) and juvenile tree shrews. In addition, recovery from lens-induced myopia was compared with the response to a similar amount of myopia produced with plus lenses in age-matched juvenile animals. Normal emmetropization was examined with daily noncycloplegic autorefractor measures from 11 days after natural eye-opening (days of visual experience [VE]) when the eyes were in the infantile, rapid growth phase and their refractions were substantially hyperopic, to 35 days of VE when the eyes had entered the juvenile, slower growth phase and the refractions were near emmetropia. Starting at 11 days of VE, two groups of young tree shrews wore binocular +4 D lenses (n =6) or −5 D lenses (n =5). Starting at 24 days of VE, four groups of juvenile tree shrews (n =5 each) wore binocular +3 D, +5 D, −3 D, or −5 D lenses. Non-cycloplegic measures of refractive state were made frequently while the animals wore the assigned lenses. The refractive response of the juvenile plus-lens wearing animals was compared with the refractive recovery of an age-matched group of animals (n =5) that were myopic after wearing a −5 D lens from 11 to 24 days of VE. In normal tree shrews, refractions (corrected for the small eye artifact) declined rapidly from (mean±SEM) 6.6±0.6 D of hyperopia at 11 VE to 1.4±0.2 D at 24 VE and 0.8±0.4 D at 35 VE. Plus 4 D lens treatment applied at 11 days of VE initially corrected or over-corrected the young animals’ hyperopia and produced a compensatory response in most animals; the eyes became nearly emmetropic while wearing the +4 D lenses. In contrast, plus-lens treatment starting at 24 days of VE initially made the juvenile eyes myopic (over-correction) and, on average, was less effective. The response ranged from no change in refractive state (eye continued to experience myopia) to full compensation (emmetropic with the lens in place). Minus-lens wear in both the young and juvenile groups, which initially made eyes more hyperopic, consistently produced compensation to the minus lens so that eyes reached age-appropriate refractions while wearing the lenses. When the minus lenses were removed, the eyes recovered quickly to age-matched normal values. The consistent recovery response from myopia in juvenile eyes after minus-lens compensation, compared with the highly variable response to plus lens wear in age-matched juvenile animals suggests that eyes retain the ability to detect the myopic refractive state, but there is an age-related decrease in the ability of normal eyes to use myopia to slow their elongation rate below normal. If juvenile human eyes, compared with infants, have a similar difficulty in using myopia to slow axial elongation, this may contribute to myopia development, especially in eyes with a genetic pre-disposition to elongate. [Copyright &y& Elsevier]

Abstract: Although the blood oxygenation level dependent (BOLD) signal used in most functional magnetic resonance imaging (fMRI) studies has been shown to exhibit nonlinear characteristics, most analyses assume that the BOLD signal responds in a linear fashion to stimulus. This assumption of linearity can lead to errors in the estimation of the BOLD response, especially for rapid event-related fMRI studies. In this study, we used a rapid event-related design and Volterra kernel analysis to assess the effect of a 200 mg oral dose of caffeine on the linearity of the visual BOLD response. The caffeine dose significantly (p <0.02) increased the linearity of the BOLD response in a sample of 11 healthy volunteers studied on a 3 T MRI system. In addition, the agreement between nonlinear and linear estimates of the hemodynamic response function was significantly increased (p =0.013) with the caffeine dose. These findings indicate that differences in caffeine usage should be considered as a potential source of bias in the analysis of rapid event-related fMRI studies. [Copyright &y& Elsevier]

Abstract: For quadrupolar nuclei with spin quantum numbers equal to 3/2, 5/2 and 7/2, the intensities of the NMR transitions in a single crystal are examined as a function of the rf excitation flip angle. Single-quantum NMR intensities are calculated using density matrix theory beginning under various non-equilibrium conditions and are compared with those determined experimentally. As a representative spin-3/2 system, the flip-angle dependence of the 23Na NMR intensities of a single crystal of NaNO3 was investigated beginning with the inversion of the populations associated with one of the satellite transitions. Subsequently, the populations of both satellite transitions were inverted using highly frequency-selective hyperbolic secant pulses. Calculated and experimental intensities are in good agreement. As an example of a spin-5/2 system, the flip-angle dependence of the 27Al NMR transition intensities was determined using a single crystal of sapphire, Al2O3, starting under different nuclear spin population conditions. The experimental trends mimicked those predicted by the density matrix calculations but the agreement was not as good as for the spin-3/2 case. Some SIMPSON simulations were also carried out to confirm the results generated by our density matrix calculations. The theoretical flip-angle behavior of the NMR transition intensities obtained from a spin-7/2 spin system is also discussed. [Copyright &y& Elsevier]

Abstract: The proliferative capacity of cancer cells is regulated by factors intrinsic to cancer cells and by secreted factors in the microenvironment. Here, we investigated the proto-oncogenic potential of the chemokine receptor, CCR5, in MCF-7 breast cancer cell lines. At physiological levels, CCL5, a ligand for CCR5, enhanced MCF-7.CCR5 proliferation. Treatment with the mTOR inhibitor, rapamycin, inhibited this CCL5-inducible proliferation. Because mTOR directly modulates mRNA translation, we investigated whether CCL5 activation of CCR5 leads to increased translation. CCL5 induced the formation of the eIF4F translation initiation complex through an mTOR-dependent process. Indeed, CCL5 initiated mRNA translation, shown by an increase in high-molecular-weight polysomes. Specifically, we show that CCL5 mediated a rapid up-regulation of protein expression for cyclin D1, c-Myc and Dad-1, without affecting their mRNA levels. Taken together, we describe a mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs, thereby providing CCR5-positive breast cancer cells with a proliferative advantage. [Copyright &y& Elsevier]

Abstract: In the application of hypercapnic normalization to functional magnetic resonance imaging (fMRI) studies, the blood oxygenation level dependent (BOLD) response to a functional stimulus is typically divided by the BOLD response to a hypercapnic challenge. While some prior studies have shown that hypercapnic normalization can reduce inter-subject BOLD variability, other studies have found an increase in inter-subject variability. In this study we used measures of baseline cerebral blood flow (CBF) and the functional BOLD and CBF responses to both visual stimuli and hypercapnia to assess the effect of hypercapnic normalization on inter-subject variability. We found that the functional and hypercapnic BOLD and CBF responses all exhibited a significant inverse dependence on baseline CBF. In contrast, the maximum BOLD response was independent of baseline CBF and was not a major source of inter-subject BOLD variability. Division of the functional BOLD response by the hypercapnic BOLD response increased inter-subject variability in the normalized responses as compared to the original responses, reflecting the presence of a systematic bias term that was inversely dependent on the hypercapnic BOLD response. This systematic bias resulted from a positive intercept term in the linear relationship between the functional and hypercapnic BOLD responses. This positive intercept term reflected a steeper inverse dependence of the hypercapnic CBF response on baseline CBF, as compared to the functional CBF response. In contrast to the results obtained with normalization based on division, normalized responses obtained by using the hypercapnic BOLD response as a covariate were unaffected by the systematic bias and exhibited reduced inter-subject variability. The findings of this study indicate that the positive intercept in the linear relationship between functional and hypercapnic BOLD responses should be carefully considered in the hypercapnic normalization of BOLD fMRI data. [Copyright &y& Elsevier]

Abstract: We test the efficacy of using a single Lagrangian point to represent a sphere, and a one-dimensional array of such points to represent a slender body, in a new immersed boundary method for Stokes flow. A numerical parameter, the spacing of the Eulerian grid, is used to determine the effective radius of the immersed sphere or slender body. Such representations are much less expensive computationally than those with two or three-dimensional meshes of Lagrangian points. To perform this test, we develop a numerical method to solve the discretized Stokes equations on an unbounded Eulerian grid which contains an arbitrary configuration of Lagrangian points that apply force to the fluid and that move with the fluid. We compare results computed with this new immersed boundary method to known results for spheres and rigid cylinders in Stokes flow in . We find that, for certain choices of parameters, the interactions with the fluid of a single Lagrangian point accurately replicate those of a sphere of some particular radius, independent of the location of the point with respect to the Eulerian grid. The interactions of a linear array of Lagrangian points, for certain choices of parameters, accurately replicate those of a cylinder of some particular radius, independent of the position and orientation of the array with respect to the Eulerian grid. The effective radius of the sphere and the effective radius of the cylinder turn out to be related in a simple and natural way. Our results suggest recipes for choosing parameters that should be useful to practitioners. One surprising result is that one must not use too many Lagrangian points in an array. Another is that the approximate delta functions traditionally used in the immersed boundary method perform much better than higher order delta functions with the same support. [Copyright &y& Elsevier]

Abstract: The experimental factors influencing the enhancements achievable for the central NMR transition, m I =1/2→ m I =−1/2, of spin-3/2 and spin-5/2 nuclei in the solid state using hyperbolic secant, HS, pulses for population transfer are investigated. In the case of powder samples spinning at the magic angle, it is found that the spinning frequency, the bandwidth and the frequency offset of the HS pulse play a crucial role in determining the maximum enhancements. Specifically, the bandwidth must be set to the spinning frequency for maximum signal enhancements. The 87Rb NMR enhancement obtained for RbClO4 using HS pulses was relatively insensitive to the magic angle spinning frequency; however, in the case of Al(acac)3, the 27Al enhancement increased with MAS frequency. In order to obtain an adiabatic HS sweep, one should optimize the rf field for a given pulse duration or optimize the pulse duration for a given rf field. [Copyright &y& Elsevier]

Abstract: Localized changes in oxygen consumption related to increased neural activity can result in a small and transient “initial dip” of the blood oxygenation level-dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI). The initial dip has been of great interest to the fMRI community because it may provide a more accurate and localized measure of neural activity than the conventional BOLD signal increase. Although potentially useful as a technique for human brain mapping, the initial dip is not always detected and has been a source of some controversy. In this study, the BOLD response to a 4-s long visual stimulus was measured with a 3-T MRI system in 5 healthy volunteers both before and immediately after a 200-mg oral caffeine dose. The caffeine dose significantly (P < 0.001) reduced or eliminated the initial dip in all subjects. These findings suggest that caffeine usage may be a key factor in the detection of the initial dip in human fMRI studies. [Copyright &y& Elsevier]

Abstract: This paper addresses the problem of creating a human-centered computer-based support environment to facilitate innovation and creative work. It focuses on key factors to be considered in the design and development of any such user support environment regardless of the specific domain for which it may be implemented. The paper reviews psychological literature on how creativity, insight and innovation occur and how they can be fostered in working environments. Based on this discussion the paper then describes a generic set of user or functional requirements intended to apply to any domain-specific computer-based working environment for support of creative activities. The paper proposes the conceptual model of a Virtual Workbench as a way of capturing some of these requirements and as a way of organizing thinking about the design of creative problem solving environments (CPSEs) in general. Finally, the paper proposes one possible translation of the Virtual Workbench and some of the functional requirements into a view of a generic model for CPSEs by describing three component sets of functions that would be a subset of those needed in almost any domain-specific CPSE. [Copyright &y& Elsevier]

Abstract: Although functional magnetic resonance imaging (fMRI) is a widely used and powerful tool for studying brain function, the quantitative interpretation of fMRI measurements for basic neuroscience and clinical studies can be complicated by inter-subject and inter-session variability arising from modulation of the baseline vascular state by disease, aging, diet, and pharmacological agents. In particular, recent studies have shown that the temporal dynamics of the cerebral blood flow (CBF) and the blood oxygenation level dependent (BOLD) responses to stimulus are modulated by changes in baseline CBF induced by various vasoactive agents and by decreases in vascular compliance associated with aging. These effects are not readily explained using current models of the CBF and BOLD responses. We present here a second-order nonlinear feedback model of the evoked CBF response in which neural activity modulates the compliance of arteriolar smooth muscle. Within this model framework, the baseline vascular state affects the dynamic response by changing the relative contributions of an active smooth muscle component and a passive connective tissue component to the overall vessel compliance. Baseline dependencies of the BOLD signal are studied by coupling the arteriolar compliance model with a previously described balloon model of the venous compartment. Numerical simulations show that the proposed model describes to first order the observed dependence of CBF and BOLD responses on the baseline vascular state. [Copyright &y& Elsevier]

Abstract: A model of the signal path in arterial spin labeling (ASL)-based functional magnetic resonance imaging (fMRI) is presented. Three subtraction-based methods for forming a perfusion estimate are considered and shown to be specific cases of a generalized estimate consisting of a modulator followed by a low pass filter. The performance of the methods is evaluated using the signal model. Contamination of the perfusion estimate by blood oxygenation level dependent contrast (BOLD) is minimized by using either sinc subtraction or surround subtraction for block design experiments and by using pair-wise subtraction for randomized event-related experiments. The subtraction methods all tend to decorrelate the 1/f type low frequency noise often observed in fMRI experiments. Sinc subtraction provides the flattest noise power spectrum at low frequencies, while pair-wise subtraction yields the narrowest autocorrelation function. The formation of BOLD estimates from the ASL data is also considered and perfusion weighting of the estimates is examined using the signal model. [Copyright &y& Elsevier]

The blood oxygenation level-dependent (BOLD) responses to visual stimuli, using both a 1-s long single trial stimulus and a 20-s long block stimulus, were measured in a 4-T magnetic field both before and immediately after a 200-mg caffeine dose. In addition, resting levels of cerebral blood flow (CBF) were measured using arterial spin labeling. For the single trial stimulus, the caffeine dose significantly (p &#60; 0.05) reduced the time to peak (TTP), the time after the peak at which the response returned to 50% of the peak amplitude (TA50), and the amplitude of the poststimulus undershoot in all subjects (N = 5). Other parameters, such as the full-width half-maximum (FWHM) and the peak amplitude, also showed significant changes in the majority of subjects. For the block stimulus, the TTP, TA50, and the time for the response to reach 50% of the peak amplitude (T50) were significantly reduced. In some subjects, oscillations were observed in the poststimulus portion of the response with median peak periods of 9.1 and 9.5 s for the single trial and block responses, respectively. Resting CBF was reduced by an average of 24%. The reproducibility of the results was verified in one subject who was scanned on 3 different days. The dynamic changes are similar to those previously reported for baseline CBF reductions induced by hypocapnia and hyperoxia. [Copyright &y& Elsevier]

The performance of an experimental design for functional magnetic resonance imaging (fMRI) can be characterized by its estimation efficiency, which is the ability to make an estimate of the hemodynamic response, its detection power, which is the ability to detect an activation, and its conditional entropy, which is a measure of the randomness of the design. In Liu and Frank [Neuroimage 21 (2004) 387–400], it is shown that there is a fundamental theoretical trade-off between estimation efficiency and detection power for experiments with multiple trial types and that there is an empirical relation between estimation efficiency and conditional entropy. This paper provides an intuitive interpretation of the theoretical results and examines the practical implications of these results for the optimal design of fMRI experiments with multiple trial types. The properties of block designs, permuted block designs, m-sequence designs, clustered m-sequence designs, and mixed designs are explored. It is shown that these designs nearly achieve the theoretically predicted performance and can be used in practice to obtain advantageous trade-offs among efficiency, power, and entropy. [Copyright &y& Elsevier]

Experimental designs for functional magnetic resonance imaging (fMRI) experiments can be characterized by their estimation efficiency, which is a measure of the variance in the estimate of the hemodynamic response function (HRF), and their detection power, which is a measure of the variance in the estimate of the amplitude of functional activity. Previous studies have shown that there exists a fundamental trade-off between efficiency and power for experiments with a single trial type of interest. This paper extends the prior work by presenting a theoretical model for the relation between detection power and estimation efficiency in experiments with multiple trial types. It is shown that the trade-off between efficiency and power present in multiple-trial-type experiments is identical in form to that observed for single-trial-type experiments. Departures from the predicted trade-off due to the inclusion of basis function expansions and the assumption of correlated noise are examined. Finally, conditional entropy is introduced as measure for the randomness of a design, and an empirical relation between entropy and estimation efficiency is presented. [Copyright &y& Elsevier]

The blood-oxygen-level-dependent (BOLD) signal measured in the brain with functional magnetic resonance imaging (fMRI) during an activation experiment often exhibits pronounced transients at the beginning and end of the stimulus. Such transients could be a reflection of transients in the underlying neural activity, or they could result from transients in cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), or cerebral blood volume (CBV). These transients were investigated using an arterial spin labeling (ASL) method that allows simultaneous measurements of BOLD and CBF responses. Responses to a finger-tapping task (40-s stimulus, 80-s rest) were measured in primary motor area (M1) and supplementary motor area (SMA) in five healthy volunteers. In SMA, the average BOLD response was pronounced near the beginning and end of the stimulus, while in M1, the BOLD response was nearly flat. However, CBF responses in the two regions were rather similar, and did not exhibit the same transient features as the BOLD response in SMA. Because this suggests a hemodynamic rather than a neural origin for the transients of the BOLD response in SMA, we used a generalization of the balloon model to test the degree of hemodynamic transients required to produce the measured curves. Both data sets could be approximated with modest differences in the shapes of the CMRO2 and CBV responses. This study illustrates the utility and the limitations of using theoretical models combined with ASL techniques to understand the dynamics of the BOLD response. [Copyright &y& Elsevier]

Human pro-IGF-I Eb-peptide (hEb) and rainbow trout pro-IGF-I Ea-4-peptide (rtEa-4) have recently been shown to share unique biological activities [Gen. Comp. Endocrinol. 126 (2002) 342; Cell. Exp. Cell. Res. 280 (2002) 75]. To further understand the action mechanism of these proteins, we studied the binding properties of hEb-peptide and rtEa-4-peptide to intact human neuroblastoma cells (SK-N-F1) and membrane preparations. Human Eb-peptide and rtEa-4-peptide bind to a high-affinity binding site with an apparent dissociation constant of 3.2±1.9×10−11 and 2.9±1.8×10−11 M, respectively. Homologous displacement assay demonstrated the presence of a second binding site with an IC50 of 4.8±2.6×10−6 M for hEb-peptide and 2.1±0.6×10−6 M for rtEa-4-peptide, respectively. Competition assays showed that hEb-peptide and rtEa-4-peptide shared common binding sites, distinct from those for IGF-I and insulin. In addition, chemical cross-linking studies revealed two specific binding complexes. Our findings support the notion that the initial step of pro-IGF-I E-peptide action is mediated through the interaction with conserved and specific putative membrane receptors on neuroblastoma cells. [Copyright &y& Elsevier]

Insulin-like growth factor-I (IGF-I) is translated as a pre-pro-peptide that is posttranslationally processed to its mature form by proteolytic removal of the signal peptide and the E-domain peptide. Contrary to the mature human (h) IGF-I, the recombinant rtEa4 -peptide significantly reduced the anchorage-independent cell growth in human neuroblastoma cells (SK-N-F1), shown by colony formation assay in vitro. Significant inhibition of colony formation is also observed in SK-N-F1 cells stably transfected with a bicistronic expression construct encoding a secretory form of the rtEa4 peptide. Furthermore, treatment with the recombinant rtEa4 peptide, but not the mature hIGF-I, resulted in morphological differentiation of SK-N-F1 cells characterized by long neurite outgrowth. Similar morphological differentiation is also observed in SK-N-F1 cell clones stably transfected with the rtEa4 peptide expression construct. A spectrum of biological activities similar to those of rtEa4 peptide is also observed in the synthetic hEb peptide, but not-the hEa peptide. Results of further characterization reveal that neurites induced by rtEa4 or hEb peptide contain neuronal-specific MAP-2, Tau, and neurofilament (NF-160), accompanied by an increased expression of the neuronal marker gene neuropeptide tyrosine (NPY). Furthermore, effects of signal transduction inhibitors are indicative of the involvement of MAP-kinase PI-3-kinase cascades. The activation of ERK-1/-2 is markedly increased in response to rtEa-4 or hEb peptide stimulation, further indicating the involvement of MAPK signaling cascade. These unique biological activities exhibited by the rtEa4 or hEb peptide suggest that E peptide of the pro-IGF-I may play distinct roles in regulating cell growth and differentiation in neuroblastoma cells. [Copyright &y& Elsevier]

Time perception is critical to animal behaviours requiring anticipation of future events based on present information about the environment. Most models of animal foraging assume that animals are capable of measuring absolute time despite evidence that animals measure time with predictable biases in mean and variance. We incorporate the evidence for a rate-biased subjective time perception into a classic model of optimal foraging, the marginal value theorem. If acceleration of the clock rate is proportional to food intake rate and time is perceived similarly when in transit between patches as it is while waiting in a patch following eating, organisms are predicted to follow the predictions of the marginal value theorem exactly. However, a nonlinear relationship between clock rate and food intake rate, unequal wait and transit time perception, or any lag in the clock predicts characteristic suboptimal behaviour. We discuss how this mechanism for suboptimal behaviour compares with others in the literature and how it can be recognized in experiments. Copyright 2002 The Association for the Study of Animal Behaviour. Published by Elsevier Science Ltd. All rights reserved. [Copyright &y& Elsevier]

Necessary and sufficient conditions and also simple sufficient conditions are given for the self-adjoint operators associated with the second-order linear differential expressionτ(y)=1/w(−(py′)′+qy) on [a,b) to have discrete spectrum. Here the coefficients of τ are non-negative and satisfy minimal smoothness conditions. These results follow from compact embedding theorems from a weighted one-dimensional Sobolev space with norm∫ab(p∣f′∣r+q∣f∣r))1/r into a weighted Banach space with norm(∫abw∣f∣s)1/s . [Copyright &y& Elsevier]

Perfusion-based functional magnetic resonance imaging (fMRI) using arterial spin labeling (ASL) methods has the potential to provide better localization of the functional signal to the sites of neural activity compared to blood oxygenation level-dependent (BOLD) contrast fMRI. At present, experiments using ASL have been limited to simple block and periodic single-trial designs. We present here an adaptation of the general linear model to perfusion-based fMRI that enables the design and analysis of more complicated designs, such as random and semirandom event-related designs. Formulas for the least-squares estimate of the perfusion response and the F statistic for the detection of a response are derived. Exact expressions and useful approximations for detection power and estimation efficiency are presented, and it is shown that the trade-off between power and efficiency for perfusion experiments is similar to that previously observed for BOLD experiments. The least-squares estimate is compared with an estimate formed from the running subtraction of tag and control images. The running subtraction estimate is shown to be approximately equal to a temporally low-pass-filtered version of the least-squares estimate. Numerical simulations and results from ASL experiments are used to support the theoretical findings. [Copyright &y& Elsevier]

We asked if emmetropia, achieved in broadband colony lighting, is maintained in narrow-band cyan light that is well focused in the emmetropic eye, but does not allow for guidance from longitudinal chromatic aberrations (LCA) and offers minimal perceptual color cues. In addition, we examined the response to a −5 D lens in this lighting. Seven tree shrews from different litters were initially housed in broad-spectrum colony lighting. At 24 ± 1 days after eye opening (Days of Visual Experience, DVE) they were housed for 11 days in ambient narrow-band cyan light (peak wavelength 505 ± 17 nm) selected because it is in focus in an emmetropic eye. Perceptually, monochromatic light at 505 nm cannot be distinguished from white by tree shrews. While in cyan light, each animal wore a monocular −5 D lens (Cyan −5 D eyes). The fellow eye was the Cyan no-lens eye. Daily awake non-cycloplegic measures were taken with an autorefractor (refractive state) and with optical low-coherence optical interferometry (axial component dimensions). These measures were compared with the values of animals raised in standard colony fluorescent lighting: an untreated group (n = 7), groups with monocular form deprivation (n = 7) or monocular −5 D lens treatment (n = 5), or that experienced 10 days in total darkness (n = 5). Refractive state at the onset of cyan light treatment was low hyperopia, (mean ± SEM) 1.4 ± 0.4 diopters. During treatment, the Cyan no-lens eyes became myopic (−2.9 ± 0.3 D) whereas colony lighting animals remained slightly hyperopic (1.0 ± 0.2 D). Initially, refractions of the Cyan −5 D eyes paralleled the Cyan no-lens eyes. After six days, they gradually became more myopic than the Cyan no-lens eyes; at the end of treatment, the refractions were −5.4 ± 0.3 D, a difference of −2.5 D from the Cyan no-lens eyes. When returned to colony lighting at 35 ± 1 DVE, the no-lens eye refractions rapidly recovered towards emmetropia but, as expected, the refraction of the −5 D eyes remained near −5 D. Vitreous chamber depth in both eyes was consistent with the refractive changes. In narrow-band cyan lighting the emmetropization mechanism did not maintain emmetropia even though the light initially was well focused. We suggest that, as the eyes diverged from emmetropia, there were insufficient LCA cues for the emmetropization mechanism to utilize the developing myopic refractive error in order to guide the eyes back to emmetropia. However, the increased myopia in the Cyan −5 D eyes in the narrow-band light indicates that the emmetropization mechanism nonetheless detected the presence of the lens-induced refractive error and responded with increased axial elongation that partly compensated for the negative-power lens. These data support the conclusion that the emmetropization mechanism cannot maintain emmetropia in narrow-band lighting. The additional myopia produced in eyes with the −5 D lens shows that the emmetropization mechanism responds to multiple defocus-related cues, even under conditions where it is unable to use them to maintain emmetropia. [Display omitted] • In narrow-band cyan light, eyes do not remain emmetropic; myopia develops. • Wearing a −5 diopter (D) lens in cyan light produces additional myopia. • The no-lens vs. −5 D lens eye difference was less than observed in broadband light. • The emmetropization mechanism responds to both wavelength and defocus cues. [ABSTRACT FROM AUTHOR]

Compatible and incompatible groups with person or task-oriented leaders were assembled and were required to use one of four work organizations while performing a manipulative task. Interchange compatibility was determined by Schutz's (1958) FIRO-B scales and leadership style by Fiedler's (1964, 1967) least. preferred co-worker (LPC) scale. In terms of structural role theory, organizations differed in kind and amount of two forms of cooperation-coordination and collaboration-identified by O'Brien (1968). Group leaders were required to use participatory rather than supervisory leadership. Results indicated that compatible groups had higher productivity than incompatible; that collaborative groups had lower productivity than noncollaborative; that collaboration and coordination interacted in influencing group productivity. Implications and suggestions for future research were discussed. [ABSTRACT FROM AUTHOR]

Abstract We describe an analysis strategy to obtain ultrasonography-matched axial dimensions of small animal eyes using the LenStar biometer. The LenStar optical low-coherence reflectometer is an attractive device for animal research due to its high precision, non-invasiveness, and the ability to measure the axial dimensions of cornea, anterior chamber, lens, vitreous chamber, and axial length. However, this optical biometer was designed for clinical applications in human eyes and its internal analysis provides inaccurate values when used on small eyes due to species-dependent differences in refractive indices and relative axial dimensions. The LenStar uses a near infrared light source to measure optical path lengths (OPLs) that are converted by the LenStar's EyeSuite software into geometrical lengths (GLs) based on the refractive indices and axial dimensions of the human eye. We present a strategy that extracts the OPLs, determines refractive indices specific for the small animal eye of interest and then calculates corrected GLs. The refractive indices are obtained by matching the LenStar values to ultrasonography values in the same eyes. As compared to ultrasounography, we found that the internal calculations of the LenStar underestimate the axial dimensions of all ocular compartments of the tree shrew eye: anterior segment depth by 6.17 ± 4.50 % , lens thickness by 1.37 ± 3.06 % , vitreous chamber depth by 29.23 ± 2.35 % , and axial length by 10.62 ± 1.75 %. Using tree shrew-specific refractive indices, the axial dimensions closely matched those measured by ultrasonography for each compartment. Our analysis strategy can be easily translated to other species by obtaining a similar paired data set using ultrasonography and LenStar, and applying our step by step procedures. [ABSTRACT FROM AUTHOR]

Abstract In resting-state fMRI, dynamic functional connectivity (DFC) measures are used to characterize temporal changes in the brain's intrinsic functional connectivity. A widely used approach for DFC estimation is the computation of the sliding window correlation between blood oxygenation level dependent (BOLD) signals from different brain regions. Although the source of temporal fluctuations in DFC estimates remains largely unknown, there is growing evidence that they may reflect dynamic shifts between functional brain networks. At the same time, recent findings suggest that DFC estimates might be prone to the influence of nuisance factors such as the physiological modulation of the BOLD signal. Therefore, nuisance regression is used in many DFC studies to regress out the effects of nuisance terms prior to the computation of DFC estimates. In this work we examined the relationship between seed-specific sliding window correlation-based DFC estimates and nuisance factors. We found that DFC estimates were significantly correlated with temporal fluctuations in the magnitude (norm) of various nuisance regressors. Strong correlations between the DFC estimates and nuisance regressor norms were found even when the underlying correlations between the nuisance and fMRI time courses were relatively small. We then show that nuisance regression does not necessarily eliminate the relationship between DFC estimates and nuisance norms, with significant correlations observed between the DFC estimates and nuisance norms even after nuisance regression. We present theoretical bounds on the difference between DFC estimates obtained before and after nuisance regression and relate these bounds to limitations in the efficacy of nuisance regression with regards to DFC estimates. Highlights • Abbreviations: Dynamic Functional Connectivity (DFC), Nuisance Regression (NR). • DFC estimates are significantly correlated with nuisance norms (magnitude). • This happens even when raw nuisance and fMRI signals are weakly correlated. • The relation between DFC and nuisance norms can remain even after NR. • Theoretical constraints on the effects of NR are presented and verified empirically. [ABSTRACT FROM AUTHOR]

Reports of pediatric injury patterns during the COVID-19 pandemic are conflicting and lack the granularity to explore differences across regions. We hypothesized there would be considerable variation in injury patterns across pediatric trauma centers in the United States. A multicenter, retrospective study evaluating patients <18 y old with traumatic injuries meeting National Trauma Data Bank criteria was performed. Patients injured after stay-at-home orders through September 2020 ("COVID" cohort) were compared to "Historical" controls from an averaged period of equivalent dates in 2016–2019. Differences in injury type, intent, and mechanism were explored at the site level. 47,385 pediatric trauma patients were included. Overall trauma volume increased during the COVID cohort compared to the Historical (COVID 7068 patients versus Historical 5891 patients); however, some sites demonstrated a decrease in overall trauma of 25% while others had an increase of over 33%. Bicycle injuries increased at every site, with a range in percent change from 24% to 135% increase. Although the greatest net increase was due to blunt injuries, there was a greater relative increase in penetrating injuries at 7/9 sites, with a range in percent change from a 110% increase to a 69% decrease. There was considerable discrepancy in pediatric injury patterns at the individual site level, perhaps suggesting a variable impact of the specific sociopolitical climate and pandemic policies of each catchment area. Investigation of the unique response of the community during times of stress at pediatric trauma centers is warranted to be better prepared for future environmental stressors. [ABSTRACT FROM AUTHOR]

Although Insulin-like growth factor (IGF-I) has been intensively studied, the functions of E-domain peptides of pro-IGF-I, however, have been overlooked. In our laboratory, several anti-cancer activities of the E-peptide of pro-IGF-I have been identified for the longest isoforms of human and rainbow trout E-peptides. These activities include dose-dependent inhibition of colony formation, inhibition of cancer cell metastasis and invasion through matrigel, suppression of cancer-induced angiogenesis, and attenuation of expression of apoptotic genes in favor of cell death. In this study, we were able to produce two-tagged recombinant human Eb-peptide (hEb) of pro-IGF-I with a purity over 99%. With its antimicrobial peptide (AMP)-like characteristics such as binding to the cytoplasmic membrane, and the affinity to the substratum of culture plate, hEb forms a layer of interface rapidly which facilitates the attachment of breast carcinoma cells, MDA-MB-231. Furthermore, the likely conformational change of homo-dimerized hEb through a single disulfide bond, as well as the ability to trigger clathrin-mediated endocytosis may play important roles for inducing lamellipodia outspread in MDA-MB-231 cells. With the highly purified hEb-peptide, not only could we study its function(s) in detail but also the minimum requirement for cancerous cells to metastasize to a suitable environment and grow. [ABSTRACT FROM AUTHOR]

In resting-state functional MRI (rsfMRI), the correlation between blood oxygenation level dependent (BOLD) signals across different brain regions is used to estimate the functional connectivity of the brain. This approach has led to the identification of a number of resting-state networks, including the default mode network (DMN) and the task positive network (TPN). Global signal regression (GSR) is a widely used pre-processing step in rsfMRI that has been shown to improve the spatial specificity of the estimated resting-state networks. In GSR, a whole brain average time series, known as the global signal (GS), is regressed out of each voxel time series prior to the computation of the correlations. However, the use of GSR is controversial because it can introduce artifactual negative correlations. For example, it has been argued that anticorrelations observed between the DMN and TPN are primarily an artifact of GSR. Despite the concerns about GSR, there is currently no consensus regarding its use. In this paper, we introduce a new framework for understanding the effects of GSR. In particular, we show that the main effects of GSR can be well approximated as a temporal downweighting process in which the data from time points with relatively large GS magnitudes are greatly attenuated while data from time points with relatively small GS magnitudes are largely unaffected. Furthermore, we show that a limiting case of this downweighting process in which data from time points with large GS magnitudes are censored can also approximate the effects of GSR. In other words, the correlation maps obtained after GSR show a high degree of spatial similarity (including the presence of anticorrelations between the DMN and TPN) with maps obtained using only the uncensored (i.e. retained) time points. Since the data from these retained time points are unaffected by the censoring process, this finding suggests that the observed anticorrelations inherently exist in the data from time points with small GS magnitudes and are not simply an artifact of GSR. [ABSTRACT FROM AUTHOR]