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Age-related strength loss affects non-stepping balance recovery
Koushyar, Hoda; Bieryla, Kathleen A.; Nussbaum, Maury A.; Madigan, Michael L. (Public Library of Science, 2019-01-18)
Aging is associated with a higher risk of falls, and an impaired ability to recover balance after a postural perturbation is an important contributing factor. In turn, this impaired recovery ability likely stems from age-related decrements in lower limb strength. The purpose of this study was to investigate the effects of age-related strength loss on non-stepping balance recovery capability after a perturbation while standing, without constraining movements to the ankle as in prior reports. Two experiments were conducted. In the first, five young adults (ages 20–30) and six community-dwelling older adults (ages 70–80) recovered their balance, without stepping, from a backward displacement of a support surface. Balance recovery capability was quantified as the maximal backward platform displacement that a subject could withstand without stepping. The maximal platform displacement was 27% smaller among the older group (11.8±2.1 cm) vs. the young group (16.2±2.6 cm). In the second experiment, forward dynamic simulations of a two-segment, rigid-body model were used to investigate the effects of manipulating strength in the hip extensors/flexors and ankle plantar flexors/dorsiflexors. In these, typical age-related reductions in strength were included. The model predicted lower maximal platform displacements with age-related reductions only in plantar flexion and hip flexion strength. These findings support the previously reported age-related loss of balance recovery ability, and an important role for plantar flexor strength in this ability. © 2019 Koushyar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Astrocyte Mechano-Activation by High-Rate Overpressure Involves Alterations in Structural and Junctional Proteins
Hlavac, Nora; VandeVord, Pamela J. (Frontiers, 2019-02-22)
Primary blast neurotrauma represents a unique injury paradigm characterized by high-rate overpressure effects on brain tissue. One major hallmark of blast neurotrauma is glial reactivity, notably prolonged astrocyte activation. This cellular response has been mainly defined in primary blast neurotrauma by increased intermediate filament expression. Because the intermediate filament networks physically interface with transmembrane proteins for junctional support, it was hypothesized that cell junction regulation is altered in the reactive phenotype as well. This would have implications for downstream transcriptional regulation via signal transduction pathways like nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Therefore, a custom high-rate overpressure simulator was built for in vitro testing using mechanical conditions based on intracranial pressure measurements in a rat model of blast neurotrauma. Primary rat astrocytes were exposed to isolated high-ratemechanical stimulation to study cell junction dynamics in relation to their mechano-activation. First, a time course for “classical” features of reactivity was devised by evaluation of glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA) expression. This was followed by gene and protein expression for both gap junction (connexins) and anchoring junction proteins (integrins and cadherins). Signal transduction analysis was carried out by nuclear localization of two molecules, NF-kB p65 and mitogen-activated protein kinase (MAPK) p38. Results indicated significant increases in connexin-43 expression and PCNA first at 24 h post-overpressure (p < 0.05), followed by structural reactivity (via increased GFAP, p < 0.05) corresponding to increased anchoring junction dynamics at 48 h post-overpressure (p < 0.05). Moreover, increased phosphorylation of focal adhesion kinase (FAK) was observed in addition to increased nuclear localization of both p65 and p38 (p < 0.05) during the period of structural reactivity. To evaluate the transcriptional activity of p65 in the nucleus, electrophoretic mobility shift assay was conducted for a binding site on the promoter region for intracellular adhesion molecule-1 (ICAM-1), an antagonist of tight junctions. A significant increase in the interaction of nuclear proteins with the NF-kB site on the ICAM-1 corresponded to increased gene and protein expression of ICAM-1 (p < 0.05).
Convective forces increase CXCR4-dependent glioblastoma cell invasion in GL261 murine model
Cornelison, R. Chase; Brennan, Caroline E.; Kingsmore, Kathryn M.; Munson, Jennifer M. (Nature Publishing Group, 2019-11-18)
Glioblastoma is the most common and malignant form of brain cancer. Its invasive nature limits treatment efficacy and promotes inevitable recurrence. Previous in vitro studies showed that interstitial fluid flow, a factor characteristically increased in cancer, increases glioma cell invasion through CXCR4- CXCL12 signaling. It is currently unknown if these effects translate in vivo. We used the therapeutic technique of convection enhanced delivery (CED) to test if convective flow alters glioma invasion in a syngeneic GL261 mouse model of glioblastoma. The GL261 cell line was flow responsive in vitro, dependent upon CXCR4 and CXCL12. Additionally, transplanting GL261 intracranially increased the populations of CXCR4+ and double positive cells versus 3D culture. We showed that inducing convective flow within implanted tumors indeed increased invasion over untreated controls, and administering the CXCR4 antagonist AMD3100 (5 mg/kg) effectively eliminated this response. These data confirm that glioma invasion is stimulated by convective flow in vivo and depends on CXCR4 signaling. We also showed that expression of CXCR4 and CXCL12 is increased in patients having received standard therapy, when CED might be elected. Hence, targeting flow-stimulated invasion may prove beneficial as a second line of therapy, particularly in patients chosen to receive treatment by convection enhanced delivery.
Effects of coral colony morphology on turbulent flow dynamics
Hossain, Md Monir; Staples, Anne E. (2020-10-07)
Local flow dynamics play a central role in physiological processes like respiration and nutrient uptake in coral reefs. Despite the importance of corals as hosts to a quarter of all marine life, and the pervasive threats facing corals, characterizing the hydrodynamics between the branches of scleractinian corals has remained a significant challenge. Here, we investigate the effects of colony branch density and surface structure on the local flow field using three-dimensional immersed boundary, large-eddy simulations for four different colony geometries under unidirectional oncoming flow conditions. The first two colonies were from thePocilloporagenus, one with a densely branched geometry, and one with a comparatively loosely branched geometry. The second pair of geometries were derived from a scan of a singleMontipora capitatacolony, one with the roughness elements called verrucae covering the surface intact, and one with the verrucae removed. For thePocilloporacorals, we found that the mean velocity profiles changed substantially in the center of the dense colony, becoming significantly reduced at middle heights where flow penetration was poor, while the mean velocity profiles in the loosely branched colony remained similar in character from the front to the back of the colony. For theMontiporacorals, somewhat counterintuitively, the colony without verrucae produced almost double the maximum Reynolds stress magnitude above the colony compared to the colony without verrucae. This implies that the smooth colony will have enhanced mass transport and higher bed shear stress and friction velocity values relative to the colony with verrucae.
Effects of fish caudal fin sweep angle and kinematics on thrust production during low-speed thunniform swimming
Matta, Alexander; Bayandor, Javid; Battaglia, Francine; Pendar, Hodjat (The Company of Biologists, 2019-06-12)
Scombrid fish lunate caudal fins are characterized by a wide range of sweep angles. Scombrid that have small sweep-angle caudal fins move at higher swimming speeds, suggesting that smaller angles produce more thrust. Furthermore, scombrids occasionally use high angles of attack (AoA) suggesting this also has some thrust benefit. This work examined the hypothesis that a smaller sweep angle and higher AoA improved thrust in swimmers by experimentally analyzing a robophysical model. The robophysical model was tested in a water tunnel at speeds between 0.35 and 0.7 body lengths per second. Three swept caudal fins were analyzed at three different AoA, three different freestream velocities, and four different Strouhal numbers, for a total of 108 cases. Results demonstrated that the fin with the largest sweep angle of 50° resulted in lower thrust production than the 40° and 30° fins, especially at higher Strouhal numbers. Larger AoA up to 25° increased thrust production at the higher Strouhal numbers, but at lower Strouhal numbers, produced less thrust. Differences in thrust production due to fin sweep angle and AoAwere attributed to the variation in spanwise flowand leading edge vortex dynamics.
Estimation of Instantaneous Gas Exchange in Flow-Through Respirometry Systems: A Modern Revision of Bartholomew's Ztransform Method
Pendar, Hodjat; Socha, John J. (PLOS, 2015-10-14)
Flow-through respirometry systems provide accurate measurement of gas exchange over long periods of time. However, these systems have limitations in tracking rapid changes. When an animal infuses a metabolic gas into the respirometry chamber in a short burst, diffusion and airflow in the chamber gradually alter the original signal before it arrives at the gas analyzer. For single or multiple bursts, the recorded signal is smeared or mixed, which may result in dramatically altered recordings compared to the emitted signal. Recovering the original metabolic signal is a difficult task because of the inherent ill conditioning problem. Here, we present two new methods to recover the fast dynamics of metabolic patterns from recorded data. We first re-derive the equations of the well-known Z-transform method (ZT method) to show the source of imprecision in this method. Then, we develop a new model of analysis for respirometry systems based on the experimentally determined impulse response, which is the response of the system to a very short unit input. As a result, we present a major modification of the ZT method (dubbed the ‘EZT method’) by using a new model for the impulse response, enhancing its precision to recover the true metabolic signals. The second method, the generalized Z-transform (GZT) method, was then developed by generalizing the EZT method; it can be applied to any flow-through respirometry system with any arbitrary impulse response. Experiments verified that the accuracy of recovering the true metabolic signals is significantly improved by the new methods. These new methods can be used more broadly for input estimation in variety of physiological systems.
Exploring optimization strategies for improving explicit water models: Rigid n-point model and polarizable model based on Drude oscillator
Xiong, Yeyue; Onufriev, Alexey V. (PLOS, 2019-11-14)
Rigid n-point water models are widely used in atomistic simulations, but have known accuracy drawbacks. Increasing the number of point charges, as well as adding electronic polarizability, are two common strategies for accuracy improvements. Both strategies come at considerable computational cost, which weighs heavily against modest possible accuracy improvements in practical simulations. In an effort to provide guidance for model development, here we have explored the limiting accuracy of “electrostatically globally optimal” npoint water models in terms of their ability to reproduce properties of water dimer—a mimic of the condensed state of water. For a given n, each model is built upon a set of reference multipole moments (e.g. ab initio) and then optimized to reproduce water dimer total dipole moment. The models are then evaluated with respect to the accuracy of reproducing the geometry of the water dimer. We find that global optimization of the charge distribution alone can deliver high accuracy of the water model: for n = 4 or n = 5, the geometry of the resulting water dimer can be almost within 50 of the ab initio reference, which is half that of the experimental error margin. Thus, global optimization of the charge distribution of classical n-point water models can lead to high accuracy models. We also find that while the accuracy improvement in going from n = 3 to n = 4 is substantial, the additional accuracy increase in going from n = 4 to n = 5 is marginal. Next, we have explored accuracy limitations of the standard practice of adding electronic polarizability (via a Drude particle) to a “rigid base”—pre-optimization rigid n-point water model. The resulting model (n = 3) shows a relatively small improvement in accuracy, suggesting that the strategy of merely adding the polarizability to an inferior accuracy water model used as the base cannot fix the defects of the latter. An alternative strategy in which the parameters of the rigid base model are globally optimized along with the polarizability parameter is much more promising: the resulting 3-point polarizable model out-performs even the 5-point optimal rigid model by a large margin. We suggest that future development efforts consider 3- and 4-point polarizable models where global optimization of the “rigid base” is coupled to optimization of the polarizability to deliver globally optimal solutions.
Extracting Interactions between Flying Bat Pairs Using Model-Free Methods
Roy, Subhradeep; Howes, Kayla; Müller, Rolf; Butail, Sachit; Abaid, Nicole (MDPI, 2019-01-09)
Social animals exhibit collective behavior whereby they negotiate to reach an agreement, such as the coordination of group motion. Bats are unique among most social animals, since they use active sensory echolocation by emitting ultrasonic waves and sensing echoes to navigate. Bats’ use of active sensing may result in acoustic interference from peers, driving different behavior when they fly together rather than alone. The present study explores quantitative methods that can be used to understand whether bats flying in pairs move independently of each other or interact. The study used field data from bats in flight and is based on the assumption that interactions between two bats are evidenced in their flight patterns. To quantify pairwise interaction, we defined the strength of coupling using model-free methods from dynamical systems and information theory. We used a control condition to eliminate similarities in flight path due to environmental geometry. Our research question is whether these data-driven methods identify directed coupling between bats from their flight paths and, if so, whether the results are consistent between methods. Results demonstrate evidence of information exchange between flying bat pairs, and, in particular, we find significant evidence of rear-to-front coupling in bats’ turning behavior when they fly in the absence of obstacles.
Functional compartmentalization in the hemocoel of insects
Pendar, Hodjat; Aviles, Jessica; Adjerid, Khaled; Schoenewald, Caroline; Socha, John J. (Springer Nature, 2019-04-15)
The insect circulatory system contains an open hemocoel, in which the mechanism of hemolymph flow control is ambiguous. As a continuous fluidic structure, this cavity should exhibit pressure changes that propagate quickly. Narrow-waisted insects create sustained pressure differences across segments, but their constricted waist provides an evident mechanism for compartmentalization. Insects with no obvious constrictions between segments may be capable of functionally compartmentalizing the body, which could explain complex hemolymph flows. Here, we test the hypothesis of functional compartmentalization by measuring pressures in a beetle and recording abdominal movements. We found that the pressure is indeed uniform within the abdomen and thorax, congruent with the predicted behavior of an open system. However, during some abdominal movements, pressures were on average 62% higher in the abdomen than in the thorax, suggesting that functional compartmentalization creates a gradient within the hemocoel. Synchrotron tomography and dissection show that the arthrodial membrane and thoracic muscles may contribute to this dynamic pressurization. Analysis of volume change suggests that the gut may play an important role in regulating pressure by translating between body segments. Overall, this study suggests that functional compartmentalization may provide an explanation for how fluid flows are managed in an open circulatory system.
How soap bubbles freeze
Ahmadi, S. Farzad; Nath, Saurabh; Kingett, Christian M.; Yue, Pengtao; Boreyko, Jonathan B. (Springer Nature, 2019-06-18)
Droplets or puddles tend to freeze from the propagation of a single freeze front. In contrast, videographers have shown that as soap bubbles freeze, a plethora of growing ice crystals can swirl around in a beautiful effect visually reminiscent of a snow globe. However, the underlying physics of how bubbles freeze has not been studied. Here, we characterize the physics of soap bubbles freezing on an icy substrate and reveal two distinct modes of freezing. The first mode, occurring for isothermally supercooled bubbles, generates a strong Marangoni flow that entrains ice crystals to produce the aforementioned snow globe effect. The second mode occurs when using a cold stage in a warm ambient, resulting in a bottom-up freeze front that eventually halts due to poor conduction along the bubble. Blending experiments, scaling analysis, and numerical methods, the dynamics of the freeze fronts and Marangoni flows are characterized.
Improving Molecular Sensitivity in X-Ray Fluorescence Molecular Imaging (XFMI) of Iodine Distribution in Mouse-Sized Phantoms via Excitation Spectrum Optimization
Dong, Xu; Chen, Cheng; Cao, Guohua (IEEE, 2018-10-25)
X-ray fluorescence molecular imaging (XFMI) has shown great promise as a low-cost molecular imaging modality for clinical and pre-clinical applications with high sensitivity. Recently, progress has been made in enabling the XFMI technique with laboratory X-ray sources for various biomedical applications. However, the sensitivity of XFMI still needs to be improved for in vivo biomedical applications at a reasonably low radiation dose. In laboratory X-ray source-based XFMI, the main factor that limits the molecular sensitivity of XFMI is the scatter X-rays that coincide with the fluorescence X-rays from the targeted material. In this paper, we experimentally investigated the effects of excitation beam spectrum on the molecular sensitivity of XFMI, by quantitatively deriving minimum detectable concentration (MDC) under a xed surface entrance dose of 200 mR at three different excitation beam spectra. XFMI experiments were carried out on two customized mouse-sized phantoms. The result shows that the MDC can be readily increased by a factor of 5.26 via excitation spectrum optimization. Furthermore, a numerical model was developed and validated by the experimental data. The numerical model can be used to optimize XFMI system configurations to further improve the molecular sensitivity. Findings from this investigation could nd applications for in vivo pre-clinical small-animal XFMI in the future.
Latent heat of traffic moving from rest
Ahmadi, S. Farzad; Berrier, Austin S.; Doty, William M.; Greer, Pat G.; Habibi, Mohammad; Morgan, Hunter A.; Waterman, Josam H.C.; Abaid, Nicole; Boreyko, Jonathan B. (IOP Publishing, 2017-11-22)
Contrary to traditional thinking and driver intuition, here we show that there is no benefit to ground vehicles increasing their packing density at stoppages. By systematically controlling the packing density of vehicles queued at a traffic light on a Smart Road, drone footage revealed that the benefit of an initial increase in displacement for close-packed vehicles is completely offset by the lag time inherent to changing back into a ‘liquid phase’ when flowresumes. This lag is analogous to the thermodynamic concept of the latent heat of fusion, as the ‘temperature’ (kinetic energy) of the vehicles cannot increase until the traffic ‘melts’ into the liquid phase.These findings suggest that in situations where gridlock is not an issue, drivers should not decrease their spacing during stoppages in order to lessen the likelihood of collisions with no loss in flowefficiency. In contrast, motion capture experiments of a line of people walking from rest showed higher flow efficiency with increased packing densities, indicating that the importance of latent heat becomes trivial for slower moving systems.
N-(3-oxododecanoyl)-L-homoserine lactone interactions in the breast tumor microenvironment: Implications for breast cancer viability and proliferation in vitro
Balhouse, Brittany N.; Patterson, Logan; Schmelz, Eva M.; Slade, Daniel J.; Verbridge, Scott S. (PLOS, 2017-07-10)
It is well documented that the tumor microenvironment profoundly impacts the etiology and progression of breast cancer, yet the contribution of the resident microbiome within breast tissue remains poorly understood. Tumor microenvironmental conditions, such as hypoxia and dense tumor stroma, predispose progressive phenotypes and therapy resistance, however the role of bacteria in this interplay remains uncharacterized. We hypothesized that the effect of individual bacterial secreted molecules on breast cancer viability and proliferation would be modulated by these tumor-relevant stressors differentially for cells at varying stages of progression. To test this, we incubated human breast adenocarcinoma cells (MDA-MB-231, MCF-DCIS.com) and non-malignant breast epithelial cells (MCF-10A) with N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), a quorum-sensing molecule from Pseudomonas aeruginosa that regulates bacterial stress responses. This molecule was selected because Pseudomonas was recently characterized as a significant fraction of the breast tissue microbiome and OdDHL is documented to impact mammalian cell viability. After OdDHL treatment, we demonstrated the greatest decrease in viability with the more malignant MDA-MB-231 cells and an intermediate MCF-DCIS.com (ductal carcinoma in situ) response. The responses were also culture condition (i.e. microenvironment) dependent. These results contrast the MCF-10A response, which demonstrated no change in viability in any culture condition. We further determined that the observed trends in breast cancer viability were due to modulation of proliferation for both cell types, as well as the induction of necrosis for MDA-MB-231 cells in all conditions. Our results provide evidence that bacterial quorum-sensing molecules interact with the host tissue environment to modulate breast cancer viability and proliferation, and that the effect of OdDHL is dependent on both cell type as well as microenvironment. Understanding the interactions between bacterial signaling molecules and the host tissue environment will allow for future studies that determine the contribution of bacteria to the onset, progression, and therapy response of breast cancer.
Numerical techniques to find optimal input parameters for achieving mean particles’ temperature and axial velocity in atmospheric plasma spray process
Batra, Romesh C.; Taetragool, Unchalisa (Nature Research, 2020)
We numerically find values of four process input parameters, namely, the argon flow rate, the hydrogen flow rate, the powder feed rate, and the current, that yield the desired mean particles’ temperature and the mean particle velocity (collectively called mean particles’ characteristics, or MPCs) in an atmospheric plasma spray process just before the particles arrive at the substrate to be coated. Previous studies have shown that the coating quality depends upon the MPCs. The process is simulated by using the software, LAVA-P-3D, that provides MPCs close to their experimental values. Thus, numerical rather than physical experiments are conducted. We first use the design of experiments to characterize the sensitivity of the MPCs to process parameters. We then identify relationships between the significant input parameters and the MPCs by using two methods, namely, the least squares regression and the response surface methodology (RSM). Finally, we employ an optimization algorithm in conjunction with the weighted sum method to find optimum values of the process input variables to achieve desired values of the MPCs. The effects of weights assigned to the objective functions for the temperature and the velocity, and the difference in using the regression and the RSM model have been studied. It is found that these values of the process parameters provide MPCs within 5% of their desired values. This methodology is applicable to other coating processes and fabrication technologies such as hot forging, machining and casting.
Oil-Impregnated Hydrocarbon-Based Polymer Films
Mukherjee, Ranit; Habibi, Mohammad; Rashed, Ziad T.; Berbert, Otacilio; Shi, Xiangke; Boreyko, Jonathan B. (Springer Nature, 2018-08-03)
Porous surfaces impregnated with a liquid lubricant exhibit minimal contact angle hysteresis with immiscible test liquids, rendering them ideal as self-cleaning materials. Rather than roughening a solid substrate, an increasingly popular choice is to use an absorbent polymer as the "porous" material. However, to date the polymer choices have been limited to expensive silicone-based polymers or complex assemblies of polymer multilayers on functionalized surfaces. In this paper, we show that hydrocarbon-based polymer films such as polyethylene can be stably impregnated with chemically compatible vegetable oils, without requiring any surface treatment. These oil-impregnated hydrocarbon-based films exhibit minimal contact angle hysteresis for a wide variety of test products including water, ketchup, and yogurt. Our oil-impregnated films remain slippery even after several weeks of being submerged in ketchup, illustrating their extreme durability. We expect that the simple and cost-effective nature of our slippery hydrocarbon-based films will make them useful for industrial packaging applications.
Paramagnetic Structures within a Microfluidic Channel for Enhanced Immunomagnetic Isolation and Surface Patterning of Cells
Sun, Chen; Hassanisaber, Hamid; Yu, Richard; Ma, Sai; Verbridge, Scott S.; Lu, Chang (Nature, 2016-07-08)
In this report, we demonstrate a unique method for embedding magnetic structures inside a microfluidic channel for cell isolation. We used a molding process to fabricate these structures out of a ferrofluid of cobalt ferrite nanoparticles. We show that the embedded magnetic structures significantly increased the magnetic field in the channel, resulting in up to 4-fold enhancement in immunomagnetic capture as compared with a channel without these embedded magnetic structures. We also studied the spatial distribution of trapped cells both experimentally and computationally. We determined that the surface pattern of these trapped cells was determined by both location of the magnet and layout of the in-channel magnetic structures. Our magnetic structure embedded microfluidic device achieved over 90% capture efficiency at a flow velocity of 4 mm/s, a speed that was roughly two orders of magnitude faster than previous microfluidic systems used for a similar purpose. We envision that our technology will provide a powerful tool for detection and enrichment of rare cells from biological samples.
A passive diffusion model of fluorescein derivatives in an in vitro human brain microvascular endothelial cell (HBMEC) monolayer
Simmons, Jamelle M.; Lee, Yong Woo; Achenie, Luke E. K. (JVE, 2018-09-29)
Eukaryotic cells have a protective plasma membrane, which restricts the free movement of molecules from the external environment to the internal environment. This study aims to computationally model the transport of fluorescein derivatives across the monolayer of human brain microvascular endothelial cells (HBMEC). The determination of plausible effective diffusion constants (𝐷eff) will allow models to be built that could be useful beyond in vitro experimentation. Fluorescein-5-isothiocyanate (FITC) modeling produced a 𝐷effrange of 1E-20 to 5E-20 cm²/s at a 1 μm cell monolayer thickness and a 𝐷eff constant near 5E-29 cm²/s at a 5 μm cell monolayer thickness. Both fluorescein and sodium fluorescein (NaFl) modeling at the 1 and 5 μm thicknesses did not produce simulations that closely resembled the HBMEC in vitro model. Overall, it is possible that the fluorescent intensity noted with fluorescein and NaFl may be better explained by a mechanism other than passive diffusion. Simulations of FITC diffusion produced a narrow range of 𝐷eff constants that closely matched the in vitro HBMEC fluorescent intensity.
Physics of chewing in terrestrial mammals
Virot, Emmanuel; Ma, Grace; Clanet, Christophe; Jung, Sungwhan (Nature, 2017-03-07)
Previous studies on chewing frequency across animal species have focused on finding a single universal scaling law. Controversy between the different models has been aroused without elucidating the variations in chewing frequency. In the present study we show that vigorous chewing is limited by the maximum force of muscle, so that the upper chewing frequency scales as the −1/3 power of body mass for large animals and as a constant frequency for small animals. On the other hand, gentle chewing to mix food uniformly without excess of saliva describes the lower limit of chewing frequency, scaling approximately as the −1/6 power of body mass. These physical constraints frame the −1/4 power law classically inferred from allometry of animal metabolic rates. All of our experimental data stay within these physical boundaries over six orders of magnitude of body mass regardless of food types.
Raman chemometric urinalysis (Rametrix) as a screen for bladder cancer
Huttanus, Herbert M.; Vu, Tommy; Guruli, Georgi; Tracey, Andrew; Carswell, William; Said, Neveen; Du, Pang; Parkinson, Bing G.; Orlando, Giuseppe; Robertson, John L.; Senger, Ryan S. (2020-08-21)
Bladder cancer (BCA) is relatively common and potentially recurrent/progressive disease. It is also costly to detect, treat, and control. Definitive diagnosis is made by examination of urine sediment, imaging, direct visualization (cystoscopy), and invasive biopsy of suspect bladder lesions. There are currently no widely-used BCA-specific biomarker urine screening tests for early BCA or for following patients during/after therapy. Urine metabolomic screening for biomarkers is costly and generally unavailable for clinical use. In response, we developed Raman spectroscopy-based chemometric urinalysis (Rametrix (TM)) as a direct liquid urine screening method for detecting complex molecular signatures in urine associated with BCA and other genitourinary tract pathologies. In particular, the Rametrix(TM)screen used principal components (PCs) of urine Raman spectra to build discriminant analysis models that indicate the presence/absence of disease. The number of PCs included was varied, and all models were cross-validated by leave-one-out analysis. In Study 1 reported here, we tested the Rametrix (TM) screen using urine specimens from 56 consented patients from a urology clinic. This proof-of-concept study contained 17 urine specimens with active BCA (BCA-positive), 32 urine specimens from patients with other genitourinary tract pathologies, seven specimens from healthy patients, and the urinalysis control Surine(TM). Using a model built with 22 PCs, BCA was detected with 80.4% accuracy, 82.4% sensitivity, 79.5% specificity, 63.6% positive predictive value (PPV), and 91.2% negative predictive value (NPV). Based on the number of PCs included, we found the Rametrix(TM)screen could be fine-tuned for either high sensitivity or specificity. In other studies reported here, Rametrix(TM)was also able to differentiate between urine specimens from patients with BCA and other genitourinary pathologies and those obtained from patients with end-stage kidney disease (ESKD). While larger studies are needed to improve Rametrix(TM)models and demonstrate clinical relevance, this study demonstrates the ability of the Rametrix(TM)screen to differentiate urine of BCA-positive patients. Molecular signature variances in the urine metabolome of BCA patients included changes in: phosphatidylinositol, nucleic acids, protein (particularly collagen), aromatic amino acids, and carotenoids.
Recovering signals in physiological systems with large datasets
Pendar, Hodjat; Socha, John J.; Chung, Julianne (Company of Biologists, 2016-08-15)
In many physiological studies, variables of interest are not directly accessible, requiring that they be estimated indirectly from noisy measured signals. Here, we introduce two empirical methods to estimate the true physiological signals from indirectly measured, noisy data. The first method is an extension of Tikhonov regularization to large-scale problems, using a sequential update approach. In the second method, we improve the conditioning of the problem by assuming that the input is uniform over a known time interval, and then use a least-squares method to estimate the input. These methods were validated computationally and experimentally by applying them to flow-through respirometry data. Specifically, we infused CO2 in a flow-through respirometry chamber in a known pattern, and used the methods to recover the known input from the recorded data. The results from these experiments indicate that these methods are capable of subsecond accuracy. We also applied the methods on respiratory data from a grasshopper to investigate the exact timing of abdominal pumping, spiracular opening, and CO2 emission. The methods can be used more generally for input estimation of any linear system.

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