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A mathematical formulation is presented for the dynamic stress intensity factor (mode I) of a permeable penny-shaped crack subjected to a time-harmonic propagating longitudinal wave in an infinite poroelastic solid. In particular, the effect of the wave-induced fluid flow on the dynamic stress intensity factor is analyzed. The Hankel integral transform technique in conjunction with Helmholtz potential theory is used to formulate the mixed boundary-value problem as dual integral equations in the frequency domain. Using appropriate transforms, the dual integral equations can be reduced to a Fredholm integral equation of the second kind. The phenomenon of fluid flow along the crack surface has significant influences upon the frequency-dependent behavior of the dynamic stress intensity factor. The stress intensity factor monotonically decreases with increasing frequency, declining the fastest when the crack radius and the slow wave wavelength are of the same order. Such near-field information is of particular importance in predicting the crack strength subjected to oscillating loads. The characteristic frequency at which the stress intensity factor decays the fastest shifts to higher frequency values when the crack radius decreases. [ABSTRACT FROM AUTHOR]

An exact analytical solution is presented for the effective dynamic shear modulus in a heterogeneous fluid-filled poroelastic medium containing spherical inclusions. The complex and frequency-dependent properties of the derived shear modulus are solely caused by the physical mechanism of mesoscopic-scale wave-induced fluid flow whose scale is assumed to be smaller than wavelength but larger than the size of pores. Our model consists of three phases: a spherical inclusion, a shell of matrix material with different mechanical and/or hydraulic properties and an outer region of effective homogeneous medium of infinite extent. This three-phase model represents a self-consistent model or an approximate model of composite having periodically distributed inclusions. The behaviors of both the inclusion and the matrix are described by Biot's equations (1941) with standard conditions of Deresiewicz and Skalak (1963) at the inclusion-matrix interface. The effective medium is regarded as an equivalent elastic or viscoelastic material with complex and frequency-dependent moduli to be determined. The derived effective shear modulus is used to quantify the shear-wave attenuation and velocity dispersion. For the problem of fluid patchy saturation (inclusions with the same solid frame as the matrix but with a different pore fluid from that in the matrix), the gas pocket does not affect the shear attenuation and dispersion characteristic of the water-filled matrix medium at all. For the problem of double porosity structure (inclusions having a different solid frame than the matrix but the same pore fluid as the matrix), with the increase of frequency the heterogeneous medium transitions from a low-frequency state having drained inclusions and drained matrix with no pore pressure difference to a higher-frequency state having undrained inclusions and undrained matrix with no fluid communication at the inclusion's surface. The relaxation frequency at which the maximum value of inverse quality factor occurs moves to frequencies by two orders of magnitude lower if the size of a unit cell increases by one order of magnitude. Stiff inclusions imbedded in a relatively soft matrix can cause significant and observable attenuation at seismic frequency bands, but softer inclusions imbedded in a relatively stiff matrix cause very weak attenuation. The mixed heterogeneity in both the solid frame and pore fluid also has important influences on the frequency-dependent shear wave attenuation. [ABSTRACT FROM AUTHOR]

Introduction Loneliness and social isolation have been associated with worsening health-related quality of life (HRQOL), increased mortality, and other poor physical and mental health outcomes among older adults. It is believed early identification of loneliness and related patient characteristics can guide more targeted and effective interventions. The objective of this study was to measure the association between the dissemination of a loneliness resource guide and HRQOL among a sample of a Medicare Advantage population with a high propensity for loneliness. Methods A random sample of 50,000 individuals enrolled in a Medicare Advantage plan, by a national health and wellbeing company, was scored using a model to predict propensity for loneliness. The top 20% (N =10,000) of the sample, predicted to be most lonely and not eligible for Medicare before age 65 because of disability, was randomly assigned to an intervention (n =5,000) and control group (n =5,000). In October 2017 the intervention group was mailed a loneliness resource guide, which provided information, worksheets, and resources for loneliness. The content was designed to describe loneliness, educate about related risk factors, and direct individuals to appropriate resources. Health-related quality of life was measured by Healthy Days, a valid set of HRQOL measures developed by the Centers of Disease Control and Prevention (CDC), which measured the physical and mental Unhealthy Days in the past 30 days. Total Unhealthy Days (UHD) was reported as the sum of physical and mental Unhealthy Days. In September and October of 2017 the intervention and control groups were administered the Healthy Days measures, telephonically. Healthy Days data was collected again in January and February of 2018, after the intervention. A linear mixed model using repeated measures assessed the longitudinal association between the intervention group and UHD. Stratified post-hoc analyses were used to identify characteristics association with the greatest change in UHD. Results Average total UHD for the intervention group (n = 782) was 14.93 UHD (pre) and 14.17 UHD (post). Average total UHD for the control group (n = 813) was 15.35 UHD (pre) and 15.18 UHD (post). Dissemination of the loneliness resource guide was associated with a reduction of 0.58 UHD (95% CI: -2.15, +0.98) when compared to the control group. Stratified analyses identified the loneliness resource guide was associated with a reduction of 2.31 UHD (95% CI: -4.96, +0.35) compared to the control group among those without evidence of depression or disability (in the prior 2 years); Average total UHD for the intervention group (n = 262) was 11.77 UHD (pre) and 10.81 UHD (post). Average total UHD for the control group (n = 244) was 12.18 UHD (pre) and 13.53 UHD (post). Conclusions Our analyses identified the largest reduction in HRQOL among individuals with a high propensity for loneliness, who were non-disabled and without a history of depression. Future loneliness research should continue to explore this population. This research was funded by Humana Inc. was the study sponsor; no external funding was involved in this study. [ABSTRACT FROM AUTHOR]

• The exact solutions of wave scattering by a rectangular permeable crack in a fluid-saturated porous medium are derived. • The analytic solutions are used to develop an effective medium model for a porous medium with aligned cracks. • The effects of wave-induced fluid diffusion as well as crack geometry on seismic attenuation and dispersion are shown numerically. • New results are useful for extracting crack information from seismic frequency-dependent signatures with applications in exploration geophysics. It is well known that mesoscopic-scale wave-induced fluid flow (WIFF) between cracks and surrounding porous matrix is one of significant mechanisms in causing seismic dispersion and attenuation. Previous theoretical models that were used to interpret the interaction between cracks and passing waves assumed the cracks to be circular or slit-like. However, in many actual cases, the cracks can have a shape more close to a rectangle. In this paper, we develop an effective medium model to estimate the P-wave attenuation and velocity dispersion in a saturated porous rock containing a random distribution of permeable, aligned, rectangular cracks of infinitesimal thickness. This is done by combining the far-field displacement representation of the solution of a normally incident P wave scattered by a single crack and Foldy's scattering theorem. The effective low-frequency P-wave velocity predicted by the present model is asymptotically consistent with the Gassmann's theory. It is shown that thorough knowledge of the crack shape is important for understanding seismic signatures. Specifically, the WIFF relaxation frequency is mainly determined by the crack intermediate dimension, while it is insensitive to the crack largest dimension. Moreover, P-wave velocity of the rectangular crack model can be quite different from those of the circular crack model and the slit crack model, although the overall frequency-dependent trends of the velocities for different models are very similar. Analogously to the circular crack model and the slit crack model, at the normal incidence of a fast-P wave, the WIFF is found to dominate the wave attenuation and velocity dispersion. These results are helpful to estimate formation parameters from different frequency components of observed seismic data. [ABSTRACT FROM AUTHOR]

• The mode-I stress intensity factor (SIF) of a periodic array of collinear cracks in a porous medium is investigated. • This paper studies the case of fluid-saturated permeable cracks. • The interacting cracks and crack surficial permeability can significantly affect the magnitude and the frequency-dependent trend of the SIF. The dynamic (frequency-dependent) mode-I stress intensity factor (SIF) is obtained for a porous medium containing an array of equally distributed collinear cracks. Unlike previous work in which the cracks are assumed to be dry and impermeable, this paper studies the case that the crack is fluid-saturated and permeable. The cracks are under the action of a normal incidence of a time-harmonic plane longitudinal (P) wave. The interaction between the collinear cracks and the mechanism of wave-induced fluid flow (scattered slow P wave) can significantly affect the magnitude and frequency-dependent trend of the SIF, in particular at low frequencies. At low frequencies, the magnitude of the SIF increases monotonously with the decreasing distance between the adjacent cracks and can be much larger than that of a single crack, implying that the material strength can be greatly lowered by the interaction of cracks. However, at higher frequencies, the impacts of interacting cracks are negligible. The comparison with the counterpart of dry impermeable cracks reveals that the magnitude of SIF is lower than that of dry impermeable cracks owing to effective normal stress effect. Moreover, unlike the SIF of dry impermeable cracks for which a peak value is observed around elastic wave resonance frequency, the corresponding SIF of fluid-saturated permeable cracks monotonously decreases with the increasing frequency. This frequency-dependent trend is attributed to the conversion of incident energy into the slow P wave. The obtained results reveal significant influences of the presence of pore fluid and interaction of collinear cracks upon the SIF, both magnitudes and frequency-dependent trends. Such information is useful in predicting the fracture strength of saturated porous materials subjected to oscillating loads. [ABSTRACT FROM AUTHOR]

• Analytic solutions of the stress intensity factors (SIFs) of a fluid-saturated permeable crack in a poroelastic material subjected to a time-harmonic elastic wave have been derived. • Insights of effects of incident wave types, material permeability, incident angle and crack surficial permeability on the frequency-dependent behaviors of the SIFs have been obtained through numerical examples. • Because of the wave-induced fluid flow, the crack fluid can significantly change the effective normal stress so that the magnitude of mode-I SIF can be lower than that of a dry impermeable crack. In many practices, cracks are filled with fluid and their background materials can be modelled within the framework of poroelasticity. Understanding the crack-tip mechanical behaviors of such a cracked medium subjected to dynamic loads is of importance for prediction of fracture failure. In this paper, based on Biot's theory of poroelastodynamics, solutions of mode-I and mode-II dynamic stress intensity factors (SIFs) of a Griffith crack are derived for the scattering problem of oblique incidence of in-plane time-harmonic P-SV waves. The crack surfaces are assumed to be permeable, and the crack is saturated by fluid. With the aid of Fourier integral transforms, the problem is reduced to a system of coupled Fredholm integral equations with special emphasis placed on finding the near-field solution. Impacts of incident wave type, material permeability and incident angle on the frequency-dependent behaviors of the SIFs have been shown graphically. It is found that the induced fluid pressure inside the crack can significantly change the effective normal stress so that the magnitude of mode-I SIF is much lower than that of a dry impermeable crack. Furthermore, the diffusion-type fluid flow (scattered slow P wave) can greatly lower the magnitude of mode-I SIF at low frequencies (much smaller than the resonance frequency). The characteristic frequency at which the curves of SIFs decline strongest occurs when the characteristic diffusion length is of the same order of the crack size. The fluid flow can also lower mode-II SIF at low frequencies and the effects are strong in the low permeability case. Specifically, in the case of scattering of SV waves, it is shown that the maximum drop of mode-II SIF in peak with respect to that of the corresponding dry crack in an elastic medium is about 10%. The obtained results reveal significant influences of the presence of pore fluid upon the SIFs, both magnitudes and frequency-dependent trends. Such information is useful in predicting the fracture strength of saturated porous materials subjected to oscillating loads. [ABSTRACT FROM AUTHOR]

The pollution-routing problem (PRP) aims to determine a set of routes and speed over each leg of the routes simultaneously to minimize the total operational and environmental costs. A common approach to solve the PRP exactly is through speed discretization, i.e., assuming that speed over each arc is chosen from a prescribed set of values. In this paper, we keep speed as a continuous decision variable within an interval and propose new formulations for the PRP. In particular, we build two mixed-integer convex optimization models for the PRP, by employing tools from disjunctive convex programming. These are the first arc-based formulations for the PRP with continuous speed. We also derive several families of valid inequalities to further strengthen both models. We test the proposed formulations on benchmark instances. Some instances are solved to optimality for the first time. [ABSTRACT FROM AUTHOR]

Golgi Membrane Protein 1 (GOLM1) has been identified as a prime target for cancer therapy because it overexpresses in many solid tumors, increases tumor growth and metastasis and leads to unfavorable survival. Though various approaches including siRNA interference and antibody targeting have been attempted, GOLM1 has remained an un-targetable molecule because of its mainly intracellular location and the lack of domains that could possibly be interfered with by small molecules. Numerous natural anti-tumoral plant substances have been identified, while their possible function on GOLM1 has never been revealed. This is the first report to study the relationship between GOLM1 downregulation and natural anti-tumoral plant substances and the possible mechanism. Among three tested possible migration-inhibiting natural substances (Epigallocatechin gallate (EGCG), Betulinic acid (BA) and Lupeol), EGCG showed the most potent inhibition effect on GOLM1 expression and MDA-MB-231 cell migration. Knocking down GOLM1 expression further increased the EGCG treatment effect. Molecular docking prediction and following experiments suggested that EGCG may inhibit GOLM1 expression and MDA-MB-231 cells migration through HGF/HGFR/AKT/GSK-3/β-catenin/c-Myc signaling pathway. In all, EGCG is the first identified GOLM1 downregulation natural product. Silencing GOLM1 may be a novel mechanism of potentiated anti-cancer migration effects and cytotoxic effect of EGCG. In addition, this study shed a new way for cancer therapy by combination of GOLM1 silencing and EGCG treatment in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Cervical spondylotic myelopathy (CSM) is a leading cause of spinal cord dysfunction with few treatment options. Although mitochondrial dynamics are linked to a wide range of pathological changes in neurodegenerative diseases, a connection between aberrant mitochondrial dynamics and CSM remains to be illuminated. In addition, mechanisms underlying the emerging anti-inflammatory and neuroprotective effects of echinacoside (ECH), the main active ingredient of Cistanche salsa , are poorly understood. We hypothesized that excessive mitochondrial fission plays a critical role in regulating inflammatory responses in CSM, and ECH might alleviate such responses by regulating mitochondrial dynamics. To this end, we assessed the effects of ECH and Mdivi-1, a selective inhibitor of dynamin-related protein (Drp1), in a rat model of chronic cervical cord compression and activated BV2 cells. Our results showed that rats with Mdivi-1 intervention had improved motor function compared with vehicle-treated rats. Indeed, Mdivi-1 treatment attenuated pro-inflammatory cytokine expression, as well as activation of the nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, nuclear transcription factor-κB (NF-κB), and Drp1 in lesions. Compared with vehicle-treated rats, compression sites of Mdivi-1-treated animals exhibited elongated mitochondrial morphologies and reduced reactive oxygen species (ROS). Similarly, ECH-treated rats exhibited neurological recovery and suppression of inflammatory response or related signals in the lesion area after treatment. Interestingly, ECH treatment partly reversed aberrant mitochondrial fragmentation and oxidative stress within the lesion area. In vitro data suggested that ECH suppressed activated microglia by modulating activation of the NLRP3 inflammasome and NF-κB signaling. Furthermore, we observed that ECH markedly inhibited Drp1 translocation onto mitochondria, whereby it regulated mitochondrial dynamics and ROS production, which act as regulators of NLRP3 inflammasome activation and NF-κB signaling. Thus, our findings reveal that mitochondrial dynamics modulate inflammatory responses during CSM. Moreover, ECH may attenuate neuroinflammation in rats subjected to chronic cervical cord compression by regulating Drp1-dependent mitochondrial fission and activation of downstream signaling. Image 1 • Chronic compression to cervical cord leads to the mitochondrial fission event in lesion area. • Mitochondrial dynamics modulate inflammatory responses during cervical spondylotic myelopathy. • Echinacoside attenuated inflammatory responses in a rat chronic cervical cord compression model. • Neuroprotective effects of echinacoside may be associated with its role on mitochondrial dynamics and downstream signaling. [ABSTRACT FROM AUTHOR]

Atmospheric transport of black carbon (BC) from surrounding areas has been shown to impact the Tibetan environment, and clarifying the geographical source and receptor regions is crucial for providing guidance for mitigation actions. In this study, 10 trace volatile organic compounds (VOCs) sampled across Tibet are chosen as proxies to diagnose source regions and related transport of pollutants to Tibet. The levels of these VOCs in Tibet are higher than those in the Arctic and Antarctic regions but much lower than those observed at many remote and background sites in Asia. The highest VOC level is observed in the eastern region, followed by the southern region and the northern region. A positive matrix factorization (PMF) model found that three factors—industry, biomass burning, and traffic—present different spatial distributions, which indicates that different zones of Tibet are influenced by different VOC sources. The average age of the air masses in the northern and eastern regions is estimated to be 3.5 and 2.8 days using the ratio of toluene to benzene, respectively, which indicates the foreign transport of VOC species to those regions. Back-trajectory analyses show that the Afghanistan-Pakistan-Tajikistan region, Indo-Gangetic Plain (IGP), and Meghalaya-Myanmar region could transport industrial VOCs to different zones of Tibet from west to east. The agricultural bases in northern India could transport biomass burning-related VOCs to the middle-northern and eastern zones of Tibet. High traffic along the unique national roads in Tibet is associated with emissions from local sources and neighboring areas. Our study proposes international joint-control efforts and targeted actions to mitigate the climatic changes and effects associated with VOCs in Tibet, which is a climate sensitive region and an important source of global water. [ABSTRACT FROM AUTHOR]