bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effects of delayed intraventricular TLR7 agonist administration on cerebral white and gray matter following asphyxia in the preterm fetal sheep
Authors: Cho Kenta H. T. , Wassink Guido , Galinsky Robert , Xu Bing , Mathai Sam , Dhillon Simerdeep K. , van den Heuij Lotte G. , Davidson Joanne O. , Weaver-Mikaere Luke , Bennet Laura , Gunn Alistair J. , Fraser Mhoyra 
Published: July 2019

AbstractPreterm brain injury is highly associated with inflammation, which is likely related in part to sterile responses to hypoxia-ischemia. We have recently shown that neuroprotection with inflammatory pre-conditioning in the immature brain is associated with induction of toll-like receptor 7 (TLR7). We therefore tested the hypothesis that central administration of a synthetic TLR7 agonist, gardiquimod (GDQ), after severe hypoxia-ischemia in preterm-equivalent fetal sheep would improve white and gray matter recovery. Fetal sheep at 0.7 of gestation received sham asphyxia or asphyxia induced by umbilical cord occlusion for 25 minutes, followed by a continuous intracerebroventricular infusion of GDQ or vehicle from 1 to 4 hours (total dose 1.8 mg/kg). Sheep were killed 72 hours after asphyxia for histology. GDQ significantly improved survival of immature and mature oligodendrocytes (2′,3′-cyclic-nucleotide 3′-phosphodiesterase, CNPase) and total oligodendrocytes (oligodendrocyte transcription factor 2, Olig-2) within the periventricular and intragyral white matter. There were reduced numbers of cells showing cleaved caspase-3 positive apoptosis and astrogliosis (glial fibrillary acidic protein, GFAP) in both white matter regions. Neuronal survival was increased in the dentate gyrus, caudate and medial thalamic nucleus. Central infusion of GDQ was associated with a robust increase in fetal plasma concentrations of the anti-inflammatory cytokines, interferon-β (IFN-β) and interleukin-10 (IL-10), with no significant change in the concentration of the pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α). In conclusion, delayed administration of the TLR7 agonist, GDQ, after severe hypoxia-ischemia in the developing brain markedly ameliorated white and gray matter damage, in association with upregulation of anti-inflammatory cytokines. These data strongly support the hypothesis that modulation of secondary inflammation may be a viable therapeutic target for injury of the preterm brain.
Improving the SERS signals of biomolecules using a stacked biochip containing Fe2O3/Au nanoparticles and a DC magnetic field
Authors: Deng Zu-Yin , Chen Kuen-Lin , Wu Chiu-Hsien 
Published: July 2019

AbstractThis study proposes a magnetic biochip that uses surface-enhanced Raman scattering (SERS) for antigen detection. The biochip was a sandwich structure containing alternating layers of gold and magnetic Fe2O3 nanoparticles. Both single (Au/Fe2O3/Au) and multilayer (Au/Fe2O3/Au/Fe2O3/Au) chips containing Fe2O3 nanoparticles were fabricated to detect bovine serum albumin (BSA). The single-layer chip detected the BSA antigen at a signal-to-noise ratio (SNR) of 5.0. Peaks detected between 1000 and 1500 cm−1 corresponded to various carbon chains. With more Fe2O3 layers, bond resonance was enhanced via the Hall effect. The distribution of electromagnetic field enhancement was determined via SERS. The signal from the single-layer chip containing Au nanoparticles was measured in an external magnetic field. Maximum signal strength was recorded in a field strength of 12.5 gauss. We observed peaks due to other carbon–hydrogen molecules in a 62.5-gauss field. The magnetic field could improve the resolution and selectivity of sample observations.
Optical fibre Fabry-Pérot interferometer based on inline microcavities for salinity and temperature sensing
Authors: Flores Raquel , Janeiro Ricardo , Viegas Jaime 
Published: July 2019

AbstractThis work explores the development of highly sensitive salinity sensors. The demonstrated sensors are based on optical fibres and consist on Fabry-Pérot optical cavities formed by optimized processes that include chemical etching and fusion splicing, on which microfluidic channels are milled by focused ion beam. Two configurations are presented and their performance compared, including a design that makes use of Vernier-effect for the simultaneous measurement of salinity and temperature with high sensitivity. The interrogation of the devices is carried out by spectral measurements using a broadband light source yielding sensitivities to salinity up to 82.61 nm/M, or 6830.0 nm/RIU.
Compensated pathogenic variants in coagulation factors VIII and IX present complex mapping between molecular impact and hemophilia severity
Authors: Marín Òscar , Aguirre Josu , de la Cruz Xavier 
Published: July 2019

AbstractCompensated pathogenic deviations (CPDs) are sequence variants that are pathogenic in humans but neutral in other species. In recent years, our molecular understanding of CPDs has advanced substantially. For example, it is known that their impact on human proteins is generally milder than that of average pathogenic mutations and that their impact is suppressed in non-human carriers by compensatory mutations. However, prior studies have ignored the evolutionarily relevant relationship between molecular impact and organismal phenotype. Here, we explore this topic using CPDs from FVIII and FIX and data concerning carriers’ hemophilia severity. We find that, regardless of their molecular impact, these mutations can be associated with either mild or severe disease phenotypes. Only a weak relationship is found between protein stability changes and severity. We also characterize the population variability of hemostasis proteins, which constitute the genetic background of FVIII and FIX, using data from the 1000 Genome project. We observe that genetic background can vary substantially between individuals in terms of both the amount and nature of genetic variants. Finally, we discuss how these results highlight the need to include new terms in present models of protein evolution to explain the origin of CPDs.
Critical Limb Ischemia Induces Remodeling of Skeletal Muscle Motor Unit, Myonuclear-, and Mitochondrial-Domains
Authors: Mohiuddin Mahir , Lee Nan Hee , Moon June Young , Han Woojin M. , Anderson Shannon E. , Choi Jeongmoon J. , Shin Eunjung , Nakhai Shadi A. , Tran Thu , Aliya Berna , Kim Do Young , Gerold Aimee , Hansen Laura M. , Taylor W. Robert , Jang Young C. 
Published: July 2019

AbstractCritical limb ischemia, the most severe form of peripheral artery disease, leads to extensive damage and alterations to skeletal muscle homeostasis. Although recent research has investigated the tissue-specific responses to ischemia, the role of the muscle stem cell in the regeneration of its niche components within skeletal muscle has been limited. To elucidate the regenerative mechanism of the muscle stem cell in response to ischemic insults, we explored cellular interactions between the vasculature, neural network, and muscle fiber within the muscle stem cell niche. Using a surgical murine hindlimb ischemia model, we first discovered a significant increase in subsynaptic nuclei and remodeling of the neuromuscular junction following ischemia-induced denervation. In addition, ischemic injury causes significant alterations to the myofiber through a muscle stem cell-mediated accumulation of total myonuclei and a concomitant decrease in myonuclear domain size, possibly to enhance the transcriptional and translation output and restore muscle mass. Results also revealed an accumulation of total mitochondrial content per myonucleus in ischemic myofibers to compensate for impaired mitochondrial function and high turnover rate. Taken together, the findings from this study suggest that the muscle stem cell plays a role in motor neuron reinnervation, myonuclear accretion, and mitochondrial biogenesis for skeletal muscle regeneration following ischemic injury.
Single-cell RNA-seq variant analysis for exploration of genetic heterogeneity in cancer
Authors: Fasterius Erik , Uhlén Mathias , Al-Khalili Szigyarto Cristina 
Published: July 2019

AbstractInter- and intra-tumour heterogeneity is caused by genetic and non-genetic factors, leading to severe clinical implications. High-throughput sequencing technologies provide unprecedented tools to analyse DNA and RNA in single cells and explore both genetic heterogeneity and phenotypic variation between cells in tissues and tumours. Simultaneous analysis of both DNA and RNA in the same cell is, however, still in its infancy. We have thus developed a method to extract and analyse information regarding genetic heterogeneity that affects cellular biology from single-cell RNA-seq data. The method enables both comparisons and clustering of cells based on genetic variation in single nucleotide variants, revealing cellular subpopulations corroborated by gene expression-based methods. Furthermore, the results show that lymph node metastases have lower levels of genetic heterogeneity compared to their original tumours with respect to variants affecting protein function. The analysis also revealed three previously unknown variants common across cancer cells in glioblastoma patients. These results demonstrate the power and versatility of scRNA-seq variant analysis and highlight it as a useful complement to already existing methods, enabling simultaneous investigations of both gene expression and genetic variation.
Influence of the spatial confinement on the self-focusing of ultrashort pulses in hollow-core fibers
Authors: Crego Aurora , Conejero Jarque Enrique , San Roman Julio 
Published: July 2019

AbstractThe collapse of a laser beam propagating inside a hollow-core fiber is investigated by numerically solving different nonlinear propagation models. We have identified that the fiber confinement favors the spatial collapse, especially in case of pulses with the input peak power close to the critical value. We have also observed that when using pulses in the femtosecond range, the temporal dynamics plays an important role, activating the spatial collapse even for pulses with input peak powers below the critical value. The complex self-focusing dynamics observed in the region below the critical power depends on the temporal evolution of the pulse and, also, on the interaction between the different spatial modes of the hollow-core fiber.
Forming individual magnetic biskyrmions by merging two skyrmions in a centrosymmetric nanodisk
Authors: Göbel Börge , Henk Jürgen , Mertig Ingrid 
Published: July 2019

AbstractWhen two magnetic skyrmions – whirl-like, topologically protected quasiparticles – form a bound pair, a biskyrmion state with a topological charge ofNSk = ±2 is constituted. Recently, especially the case of two partially overlapping skyrmions has brought about great research interest. Since for its formation the individual skyrmions need to posses opposite in-plane magnetizations, such a biskyrmion cannot be stabilized by the Dzyaloshinskii-Moriya-interaction (DMI), which is the interaction that typically stabilizes skyrmions in non-centrosymmetric materials and at interfaces. Here, we show that these biskyrmions can be stabilized by the dipole-dipole interaction in centrosymmetric materials in which the DMI is forbidden. Analytical considerations indicate that the bound state of a biskyrmion is energetically preferable over two individual skyrmions. As a result, when starting from two skyrmions in a micromagnetic simulation, a biskyrmion is formed upon relaxation. We propose a scheme that allows to control this biskyrmion formation in nanodisks and analyze the individual steps.
Inhibition of Cathepsin S Reduces Lacrimal Gland Inflammation and Increases Tear Flow in a Mouse Model of Sjögren’s Syndrome
Authors: Klinngam Wannita , Janga Srikanth R. , Lee Changrim , Ju Yaping , Yarber Frances , Shah Mihir , Guo Hao , Wang Dandan , MacKay J. Andrew , Edman Maria C. , Hamm-Alvarez Sarah F. 
Published: July 2019

AbstractCathepsin S (CTSS) is highly increased in Sjögren’s syndrome (SS) patients tears and in tears and lacrimal glands (LG) of male non-obese diabetic (NOD) mice, a murine model of SS. To explore CTSS’s utility as a therapeutic target for mitigating ocular manifestations of SS in sites where CTSS is increased in disease, the tears and the LG (systemically), the peptide-based inhibitor, Z-FL-COCHO (Z-FL), was administered to 14–15 week male NOD mice. Systemic intraperitoneal (i.p.) injection for 2 weeks significantly reduced CTSS activity in tears, LG and spleen, significantly reduced total lymphocytic infiltration into LG, reduced CD3+ and CD68+ cell abundance within lymphocytic infiltrates, and significantly increased stimulated tear secretion. Topical administration of Z-FL to a different cohort of 14–15 week male NOD mice for 6 weeks significantly reduced only tear CTSS while not affecting LG and spleen CTSS and attenuated the disease-progression related reduction of basal tear secretion, while not significantly impacting lymphocytic infiltration of the LG. These findings suggest that CTSS inhibitors administered either topically or systemically can mitigate aspects of the ocular manifestations of SS.
Tunnel magnetoresistance angular and bias dependence enabling tuneable wireless communication
Authors: Kowalska Ewa , Fukushima Akio , Sluka Volker , Fowley Ciarán , Kákay Attila , Aleksandrov Yuriy , Lindner Jürgen , Fassbender Jürgen , Yuasa Shinji , Deac Alina M. 
Published: July 2019

AbstractSpin-transfer torques (STTs) can be exploited in order to manipulate the magnetic moments of nanomagnets, thus allowing for new consumer-oriented devices to be designed. Of particular interest here are tuneable radio-frequency (RF) oscillators for wireless communication. Currently, the structure that maximizes the output power is an Fe/MgO/Fe-type magnetic tunnel junction (MTJ) with a fixed layer magnetized in the plane of the layers and a free layer magnetized perpendicular to the plane. This structure allows for most of the tunnel magnetoresistance (TMR) to be converted into output power. Here, we experimentally and theoretically demonstrate that the main mechanism sustaining steady-state precession in such structures is the angular dependence of the magnetoresistance. The TMR of such devices is known to exhibit a broken-linear dependence versus the applied bias. Our results show that the TMR bias dependence effectively quenches spin-transfer-driven precession and introduces a non-monotonic frequency dependence at high applied currents. This has an impact on devices seeking to work in the ‘THz gap’ due to their non-trivial TMR bias dependences.
Diffraction-limited axial scanning in thick biological tissue with an aberration-correcting adaptive lens
Authors: Philipp Katrin , Lemke Florian , Scholz Stefan , Wallrabe Ulrike , Wapler Matthias C. , Koukourakis Nektarios , Czarske Jürgen W. 
Published: July 2019

AbstractDiffraction-limited deep focusing into biological tissue is challenging due to aberrations that lead to a broadening of the focal spot. The diffraction limit can be restored by employing aberration correction for example with a deformable mirror. However, this results in a bulky setup due to the required beam folding. We propose a bi-actuator adaptive lens that simultaneously enables axial scanning and the correction of specimen-induced spherical aberrations with a compact setup. Using the bi-actuator lens in a confocal microscope, we show diffraction-limited axial scanning up to 340 μm deep inside a phantom specimen. The application of this technique to in vivo measurements of zebrafish embryos with reporter-gene-driven fluorescence in a thyroid gland reveals substructures of the thyroid follicles, indicating that the bi-actuator adaptive lens is a meaningful supplement to the existing adaptive optics toolset.
Identification of dominant gas transport frequencies during barometric pumping of fractured rock
Authors: Harp Dylan R. , Ortiz John P. , Stauffer Philip H. 
Published: July 2019

AbstractWe demonstrate that although barometric pressures are complicated signals comprised of numerous frequencies, it is a subset of these frequencies that drive the overwhelming majority of gas transport in fractured rock. Using an inverse numerical analysis, we demonstrate that a single barometric component with seasonally modulated amplitude approximates gas transport due to a measured barometric signal. If past barometric tendencies are expected to continue at a location, the identification of this frequency can facilitate accurate long term predictions of barometrically induced gas transport negating the need to consider stochastic realizations of future barometric variations. Additionally, we perform an analytical analysis that indicates that there is a set of barometric frequencies, consistent with the inverse numerical analysis, with high production efficiency. Based on the corroborating inverse numerical and analytical analyses, we conclude that there is a set of dominant gas transport frequencies in barometric records.
Wheat and barley can increase grain yield in shade through acclimation of physiological and morphological traits in Mediterranean conditions
Authors: Arenas-Corraliza M. G. , Rolo V. , López-Díaz M. L. , Moreno G. 
Published: July 2019

AbstractMajor cereal yields are expected to decline significantly in coming years due to the effects of climate change temperature rise. Agroforestry systems have been recognized as a useful land management strategy that could mitigate these effects through the shelter provided by trees, but it is unclear how shade affects cereal production. Most cereal species and cultivars have been selected for full light conditions, making it necessary to determine those able to acclimate to low irradiance environments and the traits that drive this acclimation. A greenhouse experiment was conducted in central Spain to assess the photosynthetic response, leaf morphology and grain yield of nine cultivars of winter wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) at three levels of photosynthetic active radiation (100%, 90% and 50%). Cultivars were selected according to three different precocity categories and were widely used in the studied area. The main objective was to assess whether the species and cultivars could acclimate to partial shade through physiological and morphological acclimations and thus increase their grain yield for cultivation in agroforestry systems. Both species increased grain yield by 19% in shade conditions. However, they used different acclimation strategies. Barley mostly performed a physiological acclimation, while wheat had a major morphological adjustment under shaded environment. Barley had lower dark respiration (42%), lower light compensation point (73%) and higher maximum quantum yield (48%) than wheat in full light conditions, revealing that it was a more shade-tolerant species than wheat. In addition, to acclimate to low irradiance conditions, barley showed a 21% reduction of the carotenoids/chlorophyll ratio in the lowest irradiance level compared to 100% light availability and adjusted the chlorophyll a/b ratio, photosystem II quantum efficiency, electron transport rate and non-photochemical quenching to shade conditions. On the other hand, wheat showed a 48% increase in single leaf area in the 50% irradiance level than in full light to maximize light capture. Our results showed that current commercialized wheat and barley cultivars had sufficient plasticity for adaptation to shade, supporting tree presence as a tool to reduce the negative effects of climate change.
Nasal delivery of donepezil HCl-loaded hydrogels for the treatment of Alzheimer’s disease
Authors: Al Harthi Sitah , Alavi Seyed Ebrahim , Radwan Mahasen Ali , El Khatib Mona Mohamed , AlSarra Ibrahim Abdullah 
Published: July 2019

AbstractThis study aims to prepare, characterize and evaluate the pharmacokinetics of liposomal donepezil HCl (LDH) dispersed into thiolated chitosan hydrogel (TCH) in rabbits. Various hydrogels including TCH were prepared, and after characterization, TCH was selected for subsequent evaluations, due to the promising results. TCH was then incorporated with LDH prepared by reverse phase evaporation method. The hydrogel was characterized using scanning electron microscope, dialysis membrane technique, and ultra-performance liquid chromatography methods. The optimized resultant was then evaluated in terms of pharmacokinetics in an in vivo environment. The mean size of LDH and drug entrapment efficiency were 438.7 ± 28.3 nm and 62.5% ± 0.6, respectively. The controlled drug release pattern results showed that the half-life of the loaded drug was approximately 3.5 h. Liposomal hydrogel and free liposomes were more stable at 4 °C compared to those in 20 °C. The pharmacokinetics study in the rabbit showed that the optimized hydrogel increased the mean peak drug concentration and area under the curve by 46% and 39%, respectively, through nasal route compared to the oral tablets of DH. Moreover, intranasal delivery of DH through liposomal hydrogel increased the mean brain content of the drug by 107% compared to the oral DH tablets. The results suggested that liposomes dispersed into TCH is a promising device for the nasal delivery of DH and can be considered for the treatment of Alzheimer’s disease.
Impact of weight variability on mortality among Korean men and women: a population based study
Authors: Choi Daein , Choi Seulggie , Park Sang Min 
Published: July 2019

AbstractThe health consequences of weight fluctuation have been controversial and little-studied within Asian populations. We aimed to determine the effect of weight variability on mortality using Korean National Health Insurance Service – National Health Screening Cohort. Weight variability was defined as the average successive variability of body mass index (BMI) of the first (2002 and 2003), second (2004 and 2005), and third (2006 and 2007) health examinations. Then, we used Cox regression models to estimate the effect of weight variability on mortality. Compared to participants within the first quintile (lowest) of weight variability, those within the fifth quintile (highest) had increased the risk of death from all causes (hazard ratio, HR 1.33, 95% confidence interval, CI 1.26–1.41), cardiovascular disease (HR 1.31, 95% CI 1.12–1.53), cancer (HR 1.11, 95% CI 1.02–1.22), and other causes (HR 1.58, 95% CI 1.45–1.73). The risk-increasing effect of weight variability on mortality was preserved after excluding past and current smokers as well as those with pre-existing cardiovascular disease or cancer. In conclusion, high weight variability may lead to elevated risk of death even among healthy never smokers. Therefore, maintaining a steady weight should be recommended to benefit from reduced risk of death.