bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moving beyond the glial scar for spinal cord repair
Authors: Bradbury Elizabeth J. , Burnside Emily R. 
Published: August 2019

AbstractTraumatic spinal cord injury results in severe and irreversible loss of function. The injury triggers a complex cascade of inflammatory and pathological processes, culminating in formation of a scar. While traditionally referred to as a glial scar, the spinal injury scar in fact comprises multiple cellular and extracellular components. This multidimensional nature should be considered when aiming to understand the role of scarring in limiting tissue repair and recovery. In this Review we discuss recent advances in understanding the composition and phenotypic characteristics of the spinal injury scar, the oversimplification of defining the scar in binary terms as good or bad, and the development of therapeutic approaches to target scar components to enable improved functional outcome after spinal cord injury.
Metabolic perceptrons for neural computing in biological systems
Authors: Pandi Amir , Koch Mathilde , Voyvodic Peter L. , Soudier Paul , Bonnet Jerome , Kushwaha Manish , Faulon Jean-Loup 
Published: August 2019

AbstractSynthetic biological circuits are promising tools for developing sophisticated systems for medical, industrial, and environmental applications. So far, circuit implementations commonly rely on gene expression regulation for information processing using digital logic. Here, we present a different approach for biological computation through metabolic circuits designed by computer-aided tools, implemented in both whole-cell and cell-free systems. We first combine metabolic transducers to build an analog adder, a device that sums up the concentrations of multiple input metabolites. Next, we build a weighted adder where the contributions of the different metabolites to the sum can be adjusted. Using a computational model fitted on experimental data, we finally implement two four-input perceptrons for desired binary classification of metabolite combinations by applying model-predicted weights to the metabolic perceptron. The perceptron-mediated neural computing introduced here lays the groundwork for more advanced metabolic circuits for rapid and scalable multiplex sensing.
Pulsed-wave Ultrasound Hyperthermia Enhanced Nanodrug Delivery Combined with Chloroquine Exerts Effective Antitumor Response and Postpones Recurrence
Authors: Chiang Chi-Feng , Hsu Yu-Hone , Liu Chih-Chun , Liang Po-Chin , Miaw Shi-Chuen , Lin Win-Li 
Published: August 2019

AbstractAutophagy is found to serve as a surviving mechanism for cancer cells. Inhibiting autophagy has been considered as an adjuvant anti-cancer strategy. In this study, we investigated the anti-tumor effect of combining pulsed-wave ultrasound hyperthermia (pUH) enhanced PEGylated liposomal doxorubicin (PLD) delivery with an autophagy inhibitor chloroquine (CQ). BALB/c mice bearing subcutaneous 4T1 tumor received intravenous injection of PLD (10 mg/kg) plus 15-minute on-tumor pUH on Day 5 after tumor implantation and were then fed with CQ (50 mg/kg daily) thereafter. Prolonged suppression of tumor growth was attained with PLD + pUH + CQ treatment, whereas in PLD + pUH group tumors quickly recurred after an initial inhibition. Treatment with CQ monotherapy had no benefit compared to the control group. Immunohistochemical staining and Western blotting showed that autophagy of cancer cells was blocked for the mice receiving CQ. It indicates that PLD + pUH + CQ is a promising strategy to treat cancer for a long-term inhibition.
Chemiosmotic energy for primitive cellular life: Proton gradients are generated across lipid membranes by redox reactions coupled to meteoritic quinones
Authors: Milshteyn Daniel , Cooper George , Deamer David 
Published: August 2019

AbstractTransmembrane proton gradients coupled to, and maintained by, electron transport are ubiquitous sources of chemiosmotic energy in all life today, but how this system first emerged is uncertain. Here we report a model liposome system in which internal ferricyanide serves as an oxidant and external ascorbate or dithionite provide a source of electrons to electron carriers embedded in liposome membranes. Quinones linked the donor to the acceptor in a coupled redox reaction that released protons into the vesicle internal volume as electrons were transported across the membranes, thereby producing substantial pH gradients. Using this system, we found that one or more quinones in extracts from carbonaceous meteorites could serve as coupling agents and that substantial pH gradients developed in the acidic interior of liposomes. If amphiphilic compounds present on the prebiotic Earth assembled into membranous compartments that separate reduced solutes in the external medium from an encapsulated acceptor, quinones can mediate electron and proton transport across the membranes, thereby providing a source of chemiosmotic energy for primitive metabolic reactions.
Global potential for the growth of fresh groundwater resources with large beach nourishments
Authors: Huizer S. , Luijendijk A. P. , Bierkens M. F. P. , Oude Essink G. H. P. 
Published: August 2019

AbstractWhether a coastal area is suitable for beach nourishments and can induce a growth in fresh groundwater resources depends on the appropriateness of the intended site for beach nourishments, and the attainable growth in fresh groundwater resources. In this study we presume that all eroding sandy beaches are suitable for large beach nourishments, and focus on the impact of these nourishments on fresh groundwater in various coastal settings. The growth in fresh groundwater resources – as a consequence of the construction of a beach nourishment – was quantified with 2-D variable-density groundwater models, for a global range in geological parameters and hydrological processes. Our simulation results suggest that large beach nourishments will likely lead to a (temporary) increase of fresh groundwater resources in most settings. However, for a substantial growth in fresh groundwater, the coastal site should receive sufficient groundwater recharge, consist of sediment with a low to medium hydraulic conductivity, and be subject to a limited number of land-surface inundations. Our global analysis shows that 17% of shorelines may consist of erosive sandy beaches, and of these sites 50% have a high potential suitability. This shows a considerable potential worldwide to combine coastal protection with an increase in fresh groundwater resources.
Latent-period stool proteomic assay of multiple sclerosis model indicates protective capacity of host-expressed protease inhibitors
Authors: Gonzalez Carlos G. , Tankou Stephanie K. , Cox Laura M. , Casavant Ellen P. , Weiner Howard L. , Elias Joshua E. 
Published: August 2019

AbstractDiseases are often diagnosed once overt symptoms arise, ignoring the prior latent period when effective prevention may be possible. Experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, exhibits such disease latency, but the molecular processes underlying this asymptomatic period remain poorly characterized. Gut microbes also influence EAE severity, yet their impact on the latent period remains unknown. Here, we show the latent period between immunization and EAE’s overt symptom onset is characterized by distinct host responses as measured by stool proteomics. In particular, we found a transient increase in protease inhibitors that inversely correlated with disease severity. Vancomycin administration attenuated both EAE symptoms and protease inhibitor induction potentially by decreasing immune system reactivity, supporting a subset of the microbiota’s role in modulating the host’s latent period response. These results strengthen previous evidence of proteases and their inhibitors in EAE and highlight the utility stool-omics for revealing complex, dynamic biology.
Structural transition in the collective behavior of cognitive agents
Authors: Hornischer Hannes , Herminghaus Stephan , Mazza Marco G. 
Published: August 2019

AbstractLiving organisms process information to interact and adapt to their surroundings with the goal of finding food, mating, or averting hazards. The structure of their environment has profound repercussions through both selecting their internal architecture and also inducing adaptive responses to environmental cues and stimuli. Adaptive collective behavior underpinned by specialized optimization strategies is ubiquitous in the natural world. We develop a minimal model of agents that explore their environment by means of sampling trajectories. The spatial information stored in the sampling trajectories is our minimal definition of a cognitive map. We find that, as cognitive agents build and update their internal, cognitive representation of the causal structure of their environment, complex patterns emerge in the system, where the onset of pattern formation relates to the spatial overlap of cognitive maps. Exchange of information among the agents leads to an order-disorder transition. As a result of the spontaneous breaking of translational symmetry, a Goldstone mode emerges, which points at a collective mechanism of information transfer among cognitive organisms. These findings may be generally applicable to the design of decentralized, artificial-intelligence swarm systems.
Molecular evidence for origin, diversification and ancient gene duplication of plant subtilases (SBTs)
Authors: Xu Yan , Wang Sibo , Li Linzhou , Sahu Sunil Kumar , Petersen Morten , Liu Xin , Melkonian Michael , Zhang Gengyun , Liu Huan 
Published: August 2019

AbstractPlant subtilases (SBTs) are a widely distributed family of serine proteases which participates in plant developmental processes and immune responses. Although SBTs are divided into seven subgroups in plants, their origin and evolution, particularly in green algae remain elusive. Here, we present a comprehensive large-scale evolutionary analysis of all subtilases. The plant subtilases SBT1-5 were found to be monophyletic, nested within a larger radiation of bacteria suggesting that they originated from bacteria by a single horizontal gene transfer (HGT) event. A group of bacterial subtilases comprising representatives from four phyla was identified as a sister group to SBT1-5. The phylogenetic analyses, based on evaluation of novel streptophyte algal genomes, suggested that the recipient of the HGT of bacterial subtilases was the common ancestor of Coleochaetophyceae, Zygnematophyceae and embryophytes. Following the HGT, the subtilase gene duplicated in the common ancestor and the two genes diversified into SBT2 and SBT1, 3–5 respectively. Comparative structural analysis of homology-modeled SBT2 proteins also showed their conservation from bacteria to embryophytes. Our study provides the first molecular evidence about the evolution of plant subtilases via HGT followed by a first gene duplication in the common ancestor of Coleochaetophyceae, Zygnematophyceae, and embryophytes, and subsequent expansion in embryophytes.
The inhibitory effect of quaternary ammonium salt on bacteria in root canal
Authors: Kumar Tiwari Sanjay , Guo Xiao , Huang Yannan , Zhou Xuedong , Xu Hockin H. K. , Ren Biao , Peng Xian , Weir Michael D. , Li Mingyun , Cheng Lei 
Published: August 2019

AbstractPersisting apical periodontitis is a primary reason for multiple intervention in root canal. Persisting bacteria in root canal is related with the persisting infection. Despite the advancement in treatment strategies the persisting infection is a major challenge for endodontist. Here we tested two newly developed quaternary ammonium methacrylates (QAMs) against endodontic bacteria and their biofilms. Their antibacterial and antibiofilm efficiency were compared with chlorhexidine (CHX) and sodium hypochlorite (NaOCl). We measured the MIC, MBC and MBIC of DMADDM and DMAHDM respectively. We also detected the ratio of live/dead bacteria and bacterial composition in the biofilms treated by DMADDM and DMAHDM. We found that DMADDM and DMAHDM could inhibit the growth of bacteria and biofilms formation. The result showed that novel QAMs were remarkably efficient than CHX against biofilms. In addition, we found that Streptococcus gordonii (S. gordonii) and Enterococcus faecalis (E. faecalis) were frequent isolates after treatment with antimicrobial compounds.
Effects of culture method on response to EGFR therapy in head and neck squamous cell carcinoma cells
Authors: Ayuso Jose M. , Vitek Ross , Swick Adam D. , Skala Melissa C. , Wisinski Kari B. , Kimple Randall J. , Lambert Paul F. , Beebe David J. 
Published: August 2019

AbstractThe EGFR pathway plays a critical role in head and neck squamous cell carcinoma (HNSCC). Targeted therapies against the EGFR are utilized as a treatment for HNSCCC. However, patient response is heterogeneous and molecular biomarkers are lacking to predict patient response. Therefore, functional assays where drug response is directly evaluated in tumor cells are an interesting alternative. Previous studies have shown that experimental conditions modify the drug response observed in functional assays. Thus, in this work the influence of the culture environment on response to Cetuximab (EGFR monoclonal antibody) and AZD8055 (mTOR inhibitor) was evaluated. HNSCC UM-SCC-1 and UM-SCC-47 cells were cultured in 2D monoculture and compared with: 2D co-culture with cancer-associated fibroblasts (CAF); 3D culture in collagen hydrogels; and 3D culture in tumor spheroids. The results showed UM-SCC-1 drug response significantly changed in the different culture environments; leading to an increase in drug resistance in the CAF co-culture and the 3D spheroids. Conversely, UM-SCC-47 exhibited a more constant drug response across culture conditions. In conclusion, this work highlights the importance of culture conditions that modulate response to EGFR pathway inhibition.
Independent Multi-states of Photo-responsive Polymer/Quantum Dot Nanocomposite Induced via Different Wavelengths of Light
Authors: Lee Jiyeon , Lee Wonsik , Kim Dongjun , Kim Myungjun , Kim Jiwon 
Published: August 2019

AbstractStimuli-responsive systems are attractive since their properties can be controlled by external stimuli and/or surrounding environment. Recently, more than one stimulus is utilized in order to enhance the performance of systems, or to bypass undesired effects. However, most of previous research on multi-stimuli has been focused on enhancing or inducing changes in one type of response. Herein, we developed a nanocomposite material with independent multi-states composed of photo-responsive polymer and quantum dots (QDs), in which its properties can independently be controlled by different wavelengths of light. More specifically, azobenzene-incorporated poly(dimethylsiloxane) (AzoPDMS) triggers photobending (PB) by 365 nm light and uniformly dispersed methylammonium lead bromide perovskite (MAPbBr3) QDs show photoluminescence (PL) by light below 500 nm. The PB and PL could be simultaneously and independently controlled by the wavelength of applied light creating multi-states. Our approach is novel in that it creates multiple independent states which can further be used to transfer information such as logic gates (00(2), 01(2), 10(2), 11(2)) and possibly widen its application to flexible and transparent opto-electric devices.
Conceptualisation, Development, Fabrication and In Vivo Validation of a Novel Disintegration Tester for Orally Disintegrating Tablets
Authors: Koner Jasdip S. , Rajabi-Siahboomi Ali R. , Missaghi Shahrzad , Kirby Daniel , Perrie Yvonne , Ahmed Jiteen , Mohammed Afzal R. 
Published: August 2019

AbstractDisintegration time is the key critical quality attribute for a tablet classed as an Orally Disintegrating Tablet (ODT). The currently accepted in vitro testing regimen for ODTs is the standard United States Pharmacopeia (USP) test for disintegration of immediate release tablets, which requires a large volume along with repeated submergence of the dosage form within the disintegration medium. The aim of this study was to develop an in vivo relevant ODT disintegration test that mimicked the environment of the oral cavity, including lower volume of disintegration medium, with relevant temperature and humidity that represent the conditions of the mouth. The results showed that the newly developed Aston test was able to differentiate between different ODTs with small disintegration time windows, as well as between immediate release tablets and ODTs. The Aston test provided higher correlations between ODT properties and disintegration time compared to the USP test method and most significantly, resulted in a linear in vitro/in vivo correlation (IVIVC) (R2 value of 0.98) compared with a “hockey stick” profile of the USP test. This study therefore concluded that the newly developed Aston test is an accurate, repeatable, relevant and robust test method for assessing ODT disintegration time which will provide the pharmaceutical industry and regulatory authorities across the world with a pragmatic ODT testing regime.
Golgin45-Syntaxin5 Interaction Contributes to Structural Integrity of the Golgi Stack
Authors: Tiwari Neeraj , Graham Morven , Liu Xinran , Yue Xihua , Zhu Lianhui , Meshram Dipak , Choi Sunkyu , Qian Yi , Rothman James E. , Lee Intaek 
Published: August 2019

AbstractThe unique stacked morphology of the Golgi apparatus had been a topic of intense investigation among the cell biologists over the years. We had previously shown that the two Golgin tethers (GM130 and Golgin45) could, to a large degree, functionally substitute for GRASP-type Golgi stacking proteins to sustain normal Golgi morphology and function in GRASP65/55-double depleted HeLa cells. However, compared to well-studied GM130, the exact role of Golgin45 in Golgi structure remains poorly understood. In this study, we aimed to further characterize the functional role of Golgin45 in Golgi structure and identified Golgin45 as a novel Syntaxin5-binding protein. Based primarily on a sequence homology between Golgin45 and GM130, we found that a leucine zipper-like motif in the central coiled-coil region of Golgin45 appears to serve as a Syntaxin5 binding domain. Mutagenesis study of this conserved domain in Golgin45 showed that a point mutation (D171A) can abrogate the interaction between Golgin45 and Syntaxin5 in pull-down assays using recombinant proteins, whereas this mutant Golgin45 binding to Rab2-GTP was unaffected in vitro. Strikingly, exogenous expression of this Syntaxin5 binding deficient mutant (D171A) of Golgin45 in HeLa cells resulted in frequent intercisternal fusion among neighboring Golgi cisterna, as readily observed by EM and EM tomography. Further, double depletion of the two Syntaxin5-binding Golgin tethers also led to significant intercisternal fusion, while double depletion of GRASP65/55 didn’t lead to this phenotype. These results suggest that certain tether-SNARE interaction within Golgi stack may play a role in inhibiting intercisternal fusion among neighboring cisternae, thereby contributing to structural integrity of the Golgi stack.
3D Printed Polyvinyl Alcohol Tablets with Multiple Release Profiles
Authors: Xu Xiaowen , Zhao Jingzhou , Wang Maonan , Wang Liang , Yang Junliang 
Published: August 2019

AbstractThe aim of this study was to explore the feasibility of using different 3D printed internal geometries as tablet formulations to obtain controlled release profiles. In order to obtain controllable release profiles, three types of tablet models (Cylinder, Horn and Reversed Horn) with controlled structures were designed. The cylinder model shows a constant release profile and can keep the drug concentration within a certain range. The horn model exhibits an increasing release profile, which is suitable for the patients who have the drug resistance in the course of medication. The reversed horn model has a decreasing release profile that would be applied to hypertension cure. Furthermore, three types of tablets were fabricated successfully by a fused deposition modeling three-dimensional (3D) printer and injected with paracetamol (APAP) -containing gels. The results of in vitro drug release demonstrate that tablets with three kinds of structures can produce constant, gradually increasing, and gradually decreasing release profiles, respectively. The release attributes can be controlled by using different 3D printed geometries as tablet formulations. More importantly, there are no residues after dissolution. The method of preparing customized tablets with distinguished release profiles presented in this study has the promising potential in the fabrication of patient-tailored medicines.
Helicity dependent diffraction by angular momentum transfer
Authors: Deepa S. , B.S. Bhargava Ram , Senthilkumaran P. 
Published: August 2019

AbstractIn this article we show that diffraction segregates the polarization singularities according to their handedness. Polarization singularities are superpositions of left and right handed circular polarization vortex states. In the superposition, the component states possess different orbital angular momenta depending on the type of the singularity. A fork grating that can generate different orbital angular momentum (OAM) states in different diffraction orders is shown to segregate right and left handed polarization singularities. A V-point polarization singularity that corresponds to one combination of OAM states incident on the fork grating is found to diffract in such a way that the same OAM combination does not occur in all the nonzero diffraction orders. As a result, each of the diffraction orders will have different polarization singularities. This OAM transfer by the fork grating segregates the right and left handed polarization singularities thereby, making the diffraction helicity dependent.
Hierarchical Template Matching for 3D Myocardial Tracking and Cardiac Strain Estimation
Authors: Bhalodiya Jayendra M. , Palit Arnab , Ferrante Enzo , Tiwari Manoj K. , Bhudia Sunil K. , Arvanitis Theodoros N. , Williams Mark A. 
Published: August 2019

AbstractMyocardial tracking and strain estimation can non-invasively assess cardiac functioning using subject-specific MRI. As the left-ventricle does not have a uniform shape and functioning from base to apex, the development of 3D MRI has provided opportunities for simultaneous 3D tracking, and 3D strain estimation. We have extended a Local Weighted Mean (LWM) transformation function for 3D, and incorporated in a Hierarchical Template Matching model to solve 3D myocardial tracking and strain estimation problem. The LWM does not need to solve a large system of equations, provides smooth displacement of myocardial points, and adapt local geometric differences in images. Hence, 3D myocardial tracking can be performed with 1.49 mm median error, and without large error outliers. The maximum error of tracking is up to 24% reduced compared to benchmark methods. Moreover, the estimated strain can be insightful to improve 3D imaging protocols, and the computer code of LWM could also be useful for geo-spatial and manufacturing image analysis researchers.