bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the size distribution of plastics ingested by animals
Authors: Jâms Ifan B. , Windsor Fredric M. , Poudevigne-Durance Thomas , Ormerod Steve J. , Durance Isabelle
Published: March 2020

The ingestion of plastics appears to be widespread throughout the animal kingdom with risks to individuals, ecosystems and human health. Despite growing information on the location, abundance and size distribution of plastics in the environment, it cannot be assumed that any given animal will ingest all sizes of plastic encountered. Here, we use published data to develop an allometric relationship between plastic consumption and animal size to estimate the size distribution of plastics feasibly ingested by animals. Based on more than 2000 gut content analyses from animals ranging over three orders of magnitude in size (lengths 9 mm to 10 m), body length alone accounts for 42% of the variance in the length of plastic an animal may ingest and indicates a size ratio of roughly 20:1 between animal body length and the largest plastic the animal may ingest. We expect this work to improve global assessments of plastic pollution risk by introducing a quantifiable link between animals and the plastics they can ingest.
Atomically dispersed cobalt catalyst anchored on nitrogen-doped carbon nanosheets for lithium-oxygen batteries
Authors: Wang Peng , Ren Yingying , Wang Rutao , Zhang Peng , Ding Mingjie , Li Caixia , Zhao Danyang , Qian Zhao , Zhang Zhiwei , Zhang Luyuan , Yin Longwei
Published: March 2020

Developing single-site catalysts featuring maximum atom utilization efficiency is urgently desired to improve oxidation-reduction efficiency and cycling capability of lithium-oxygen batteries. Here, we report a green method to synthesize isolated cobalt atoms embedded ultrathin nitrogen-rich carbon as a dual-catalyst for lithium-oxygen batteries. The achieved electrode with maximized exposed atomic active sites is beneficial for tailoring formation/decomposition mechanisms of uniformly distributed nano-sized lithium peroxide during oxygen reduction/evolution reactions due to abundant cobalt-nitrogen coordinate catalytic sites, thus demonstrating greatly enhanced redox kinetics and efficiently ameliorated over-potentials. Critically, theoretical simulations disclose that rich cobalt-nitrogen moieties as the driving force centers can drastically enhance the intrinsic affinity of intermediate species and thus fundamentally tune the evolution mechanism of the size and distribution of final lithium peroxide. In the lithium-oxygen battery, the electrode affords remarkably decreased charge/discharge polarization (0.40 V) and long-term cyclability (260 cycles at 400 mA g−1).
Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV
Authors: Ou Xiuyuan , Liu Yan , Lei Xiaobo , Li Pei , Mi Dan , Ren Lili , Guo Li , Guo Ruixuan , Chen Ting , Hu Jiaxin , Xiang Zichun , Mu Zhixia , Chen Xing , Chen Jieyong , Hu Keping , Jin Qi , Wang Jianwei , Qian Zhaohui
Published: March 2020

Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.
The biofilm-associated surface protein Esp of Enterococcus faecalis forms amyloid-like fibers
Authors: Taglialegna Agustina , Matilla-Cuenca Leticia , Dorado-Morales Pedro , Navarro Susanna , Ventura Salvador , Garnett James A. , Lasa Iñigo , Valle Jaione
Published: March 2020

Functional amyloids are considered as common building block structures of the biofilm matrix in different bacteria. In previous work, we have shown that the staphylococcal surface protein Bap, a member of the Biofilm-Associated Proteins (BAP) family, is processed and the fragments containing the N-terminal region become aggregation-prone and self-assemble into amyloid-like structures. Here, we report that Esp, a Bap-orthologous protein produced byEnterococcus faecalis, displays a similar amyloidogenic behavior. We demonstrate that at acidic pH the N-terminal region of Esp forms aggregates with an amyloid-like conformation, as evidenced by biophysical analysis and the binding of protein aggregates to amyloid-indicative dyes. Expression of a chimeric protein, with its Esp N-terminal domain anchored to the cell wall through the R domain of clumping factor A, showed that the Esp N-terminal region is sufficient to confer multicellular behavior through the formation of an extracellular amyloid-like material. These results suggest that the mechanism of amyloid-like aggregation to build the biofilm matrix might be widespread among BAP-like proteins. This amyloid-based mechanism may not only have strong relevance for bacteria lifestyle but could also contribute to the amyloid burden to which the human physiology is potentially exposed.
Environmental stress perception activates structural remodeling of extant Streptococcus mutans biofilms
Authors: Marx Patrick , Sang Yu , Qin Hua , Wang Qingjing , Guo Rongkai , Pfeifer Carmem , Kreth Jens , Merritt Justin
Published: March 2020

Transcription regulators from the LexA-like Protein Superfamily control a highly diverse assortment of genetic pathways in response to environmental stress. All characterized members of this family modulate their functionality and stability via a strict coordination with the coprotease function of RecA. Using the LexA-like protein IrvR from Streptococcus mutans, we demonstrate an exception to the RecA paradigm and illustrate how this evolutionary innovation has been coopted to diversify the stress responsiveness of S. mutans biofilms. Using a combination of genetics and biophysical measurements, we demonstrate how non-SOS stresses and SOS stresses each trigger separate regulatory mechanisms that stimulate production of a surface lectin responsible for remodeling the viscoelastic properties of extant biofilms during episodes of environmental stress. These studies demonstrate how changes in the external environment or even anti-biofilm therapeutic agents can activate biofilm-specific adaptive mechanisms responsible for bolstering the integrity of established biofilm communities. Such changes in biofilm community structure are likely to play central roles in the notorious recalcitrance of biofilm infections.
A unidirectional on-chip photonic interface for superconducting circuits
Authors: Guimond P.-O. , Vermersch B. , Juan M. L. , Sharafiev A. , Kirchmair G. , Zoller P.
Published: March 2020

We propose and analyze a passive architecture for realizing on-chip, scalable cascaded quantum devices. In contrast to standard approaches, our scheme does not rely on breaking Lorentz reciprocity. Rather, we engineer the interplay between pairs of superconducting transmon qubits and a microwave transmission line, in such a way that two delocalized orthogonal excitations emit (and absorb) photons propagating in opposite directions. We show how such cascaded quantum devices can be exploited to passively probe and measure complex many-body operators on quantum registers of stationary qubits, thus enabling the heralded transfer of quantum states between distant qubits, as well as the generation and manipulation of stabilizer codes for quantum error correction.
A hybrid stochastic model of the budding yeast cell cycle
Authors: Ahmadian Mansooreh , Tyson John J. , Peccoud Jean , Cao Yang
Published: March 2020

The growth and division of eukaryotic cells are regulated by complex, multi-scale networks. In this process, the mechanism of controlling cell-cycle progression has to be robust against inherent noise in the system. In this paper, a hybrid stochastic model is developed to study the effects of noise on the control mechanism of the budding yeast cell cycle. The modeling approach leverages, in a single multi-scale model, the advantages of two regimes: (1) the computational efficiency of a deterministic approach, and (2) the accuracy of stochastic simulations. Our results show that this hybrid stochastic model achieves high computational efficiency while generating simulation results that match very well with published experimental measurements.
A bivalent vaccine confers immunogenicity and protection against Shigella flexneri and enterotoxigenic Escherichia coli infections in mice
Authors: Medeiros Pedro Henrique Q. S. , Bolick David T. , Ledwaba Solanka E. , Kolling Glynis L. , Costa Deiziane V. S. , Oriá Reinaldo B. , Lima Aldo Ângelo M. , Barry Eileen M. , Guerrant Richard L.
Published: March 2020

Vaccine studies for Shigella flexneri and enterotoxigenic Escherichia coli have been impaired by the lack of optimal animal models. We used two murine models to show that a S. flexneri 2a bivalent vaccine (CVD 1208S-122) expressing enterotoxigenic Escherichia coli colonization factor antigen-I (CFA/I) and the binding subunits A2 and B of heat labile-enterotoxin (LTb) is immunogenic and protects against weight loss and diarrhea. These findings document the immunogenicity and pre-clinical efficacy effects of CVD 1208S-122 vaccine and suggest that further work can help elucidate relevant immune responses and ultimately its clinical efficacy in humans.
Online characterization of bacterial processes in drinking water systems
Authors: Farhat Nadia , Kim Lan Hee , Vrouwenvelder Johannes S.
Published: March 2020

The use of traditional drinking water microbial quality monitoring methods, including heterotrophic plate counts (HPCs) and total coliform counts, are not only laborious and time-consuming but also do not readily allow identification of risk areas in the network. Furthermore, if areas of concern are identified, and mitigation measures are taken, it takes days before the effectiveness of these measures is known. This study identified flow cytometry (FCM) as an online sensor technology for bacterial water quality monitoring in the distribution network. We monitored the total bacterial cell numbers and biodiversity in a drinking water distribution system (DWDS) using an online FCM. Two parallel online FCM monitoring systems were installed on two different locations at a drinking water treatment plant (DWTP; Saudi Arabia) supplying chlorinated water to the distribution and in the network 3.6 km away from the DWTP. The FCMs were operated at the same time in parallel to assess the biological stability in DWDSs. The flow cytometric data was compared with the conventional water quality detection methods (HPC and total coliforms). HPC and total coliforms were constantly below the detection limits, while the FCM provided detectable total cell count data and enabled the quantification of changes in the drinking water both with time and during distribution. Results demonstrate the value of FCM as a tool for compliance monitoring and risk assessment of DWDSs.
Sinking flux of particulate organic matter in the oceans: Sensitivity to particle characteristics
Authors: Omand Melissa M. , Govindarajan Rama , He Jing , Mahadevan Amala
Published: March 2020

The sinking of organic particles produced in the upper sunlit layers of the ocean forms an important limb of the oceanic biological pump, which impacts the sequestration of carbon and resupply of nutrients in the mesopelagic ocean. Particles raining out from the upper ocean undergo remineralization by bacteria colonized on their surface and interior, leading to an attenuation in the sinking flux of organic matter with depth. Here, we formulate a mechanistic model for the depth-dependent, sinking, particulate mass flux constituted by a range of sinking, remineralizing particles. Like previous studies, we find that the model does not achieve the characteristic ‘Martin curve’ flux profile with a single type of particle, but instead requires a distribution of particle sizes and/or properties. We consider various functional forms of remineralization appropriate for solid/compact particles, and aggregates with an anoxic or oxic interior. We explore the sensitivity of the shape of the flux vs. depth profile to the choice of remineralization function, relative particle density, particle size distribution, and water column density stratification, and find that neither a power-law nor exponential function provides a definitively superior fit to the modeled profiles. The profiles are also sensitive to the time history of the particle source. Varying surface particle size distribution (via the slope of the particle number spectrum) over 3 days to represent a transient phytoplankton bloom results in transient subsurface maxima or pulses in the sinking mass flux. This work contributes to a growing body of mechanistic export flux models that offer scope to incorporate underlying dynamical and biological processes into global carbon cycle models.
Preventive effect of fluvastatin on the development of medication-related osteonecrosis of the jaw
Authors: Adachi Naomi , Ayukawa Yasunori , Yasunami Noriyuki , Furuhashi Akihiro , Imai Mikio , Sanda Koma , Atsuta Ikiru , Koyano Kiyoshi
Published: March 2020

Medication-related osteonecrosis of the jaw (MRONJ) occurs in patients undergoing oral surgery while medicated with bisphosphonate, denosumab or anti-angiogenic agents. We employed a MRONJ-like rat model to investigate whether injecting fluvastatin at extraction sites prevents MRONJ-like lesion. A MRONJ-like model was created by treating rats with zoledronate and dexamethasone, extracting teeth, and immediately injecting fluvastatin at the extraction site. The experimental group comprised three subgroups treated with low (0.1 mg/kg; FS-L), medium (1.0 mg/kg; FS-M) and high concentrations (10 mg/kg; FS-H) of fluvastatin. Necrotic bone exposure was significantly lower in the FS-M (p = 0.028) and FS-H (p = 0.041) groups than in the MRONJ group. The distance between the edges of the epithelial surfaces was significantly shorter in the FS-M (p = 0.042) and FS-H (p = 0.041) groups. The area of necrotic bone and the necrotic bone ratio were significantly smaller in the FS-H group (p = 0.041 and p = 0.042 respectively). Bone volume fraction calculated on μ-CT images was significantly larger in the FS-H group than in the MRONJ group (p = 0.021). Our findings suggest that a single local injection of fluvastatin following tooth extraction can potentially reduce the chance of developing MRONJ-like lesion in rats.
Potential impacts of high-sensitivity creatine kinase-MB on long-term clinical outcomes in patients with stable coronary heart disease
Authors: Wu Yen-Wen , Ho Sing Kong , Tseng Wei-Kung , Yeh Hung-I , Leu Hsin-Bang , Yin Wei-Hsian , Lin Tsung-Hsien , Chang Kuan-Cheng , Wang Ji-Hung , Wu Chau-Chung , Chen Jaw-Wen
Published: March 2020

This study aimed to investigate the prognostic value of high-sensitivity creatine kinase-myocardial band or fraction (hsCK-MB) in comparison with other well-established biomarkers including heart type-fatty acid binding protein (H-FABP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with stable coronary heart disease (SCHD). A total of 1,785 patients were enrolled and followed for 36 months. The primary outcome was all-cause mortality. The secondary outcomes included cardiovascular (CV) death, acute myocardial infarction (AMI), angina-related hospitalizations, and hospitalizations for heart failure. The all-cause mortality rate was significantly higher in the high hsCK-MB group compared to the low hsCK-MB group (4.64% vs. 1.88%, p = 0.0026). After adjusting for baseline covariates, there were no significant differences for the secondary outcomes. H-FABP (≥4.226 ng/mL) was the best predictor for all-cause mortality (HR = 2.68, 95% CI = 1.28–5.62, p = 0.009) and CV death (HR = 6.84, 95% CI = 1.89–22.14, p = 0.003). The high NT-proBNP group had a higher AMI-related hospitalization rate (HR = 1.91, 95% CI = 1.00–3.65, p = 0.05). Neither the addition of hsCK-MB to any other markers nor combinations of the three markers improved the prognostic significance of CV outcomes. In conclusion, hsCK-MB was an independent predictor for all-cause mortality but not CV outcomes in patients with SCHD. Combination of hsCK-MB, H-FABP and NT-proBNP failed to improve the prognostic power for all-cause mortality or CV outcomes.
A Randomized Trial Comparing the Bowel Cleansing Efficacy of Sodium Picosulfate/Magnesium Citrate and Polyethylene Glycol/Bisacodyl (The Bowklean Study)
Authors: Hung Shih-Ya , Chen Hong-Chang , Chen William Tzu-Liang
Published: March 2020

Bowel cleansing is essential for a successful colonoscopy, but the ideal clearing agent and the volume have yet to be determined. A small-volume cleanser is important for patient compliance. This study aimed to compare the bowel cleansing efficacy, safety, tolerability, and acceptability of a 300-mL small-volume sodium picosulfate/magnesium citrate (PSMC) preparation-Bowklean with one 2-L polyethylene glycol (PEG)/bisacodyl-Klean-Prep/Dulcolax preparation under identical dietary recommendations. This multicenter, randomized, parallel-group, pre-specified noninferiority study enrolled 631 outpatients scheduled to undergo colonoscopy (Bowklean = 316 and Klean-Prep/Dulcolax = 315). After bowel preparation, an independent evaluator blinded to the subject’s treatment allocation rated the quality of the colon cleansing. Efficacy was evaluated using the Aronchick Scale and Ottawa Bowel Preparation Scale (OPBS). Safety was assessed by monitoring adverse events. Tolerability and acceptability were measured via a patient questionnaire. Bowklean was non-interior to Klean-Prep/Dulcolax in overall colon cleansing but was associated with significantly better preparation quality. Notably, Bowklean was associated with significantly greater tolerability and acceptability of bowel preparations than Klean-Prep/Dulcolax. Safety profiles did not differ significantly between the groups. Our data indicate that Bowklean is a more effective and better-tolerated bowel cleansing preparation before colonoscopy than Klean-Prep/Dulcolax. Bowklean may therefore increase positive attitudes toward colonoscopies and participation rates.
Fluorescence microscopy tensor imaging representations for large-scale dataset analysis
Authors: Vinegoni Claudio , Fumene Feruglio Paolo , Courties Gabriel , Schmidt Stephen , Hulsmans Maarten , Lee Sungon , Wang Rui , Sosnovik David , Nahrendorf Matthias , Weissleder Ralph
Published: March 2020

Understanding complex biological systems requires the system-wide characterization of cellular and molecular features. Recent advances in optical imaging technologies and chemical tissue clearing have facilitated the acquisition of whole-organ imaging datasets, but automated tools for their quantitative analysis and visualization are still lacking. We have here developed a visualization technique capable of providing whole-organ tensor imaging representations of local regional descriptors based on fluorescence data acquisition. This method enables rapid, multiscale, analysis and virtualization of large-volume, high-resolution complex biological data while generating 3D tractographic representations. Using the murine heart as a model, our method allowed us to analyze and interrogate the cardiac microvasculature and the tissue resident macrophage distribution and better infer and delineate the underlying structural network in unprecedented detail.
Inducible Antibacterial Activity in the Bacillales by Triphenyl Tetrazolium Chloride
Authors: Sierra-Zapata Laura , Álvarez Javier C. , Romero-Tabarez Magally , Silby Mark.W. , Traxler Matthew F. , Behie Scott W. , Pessotti Rita de Cassia , Villegas-Escobar Valeska
Published: March 2020

The world is in the midst of an antimicrobial resistance crisis, driving a need to discover novel antibiotic substances. Using chemical cues as inducers to unveil a microorganism’s full metabolic potential is considered a successful strategy. To this end, we investigated an inducible antagonistic behavior in multiple isolates of the order Bacillales, where large inhibition zones were produced against Ralstonia solanacearum only when grown in the presence of the indicator triphenyl tetrazolium chloride (TTC). This bioactivity was produced in a TTC-dose dependent manner. Escherichia coli and Staphylococcus sp. isolates were also inhibited by Bacillus sp. strains in TTC presence, to a lesser extent. Knockout mutants and transcriptomic analysis of B. subtilis NCIB 3610 cells revealed that genes from the L-histidine biosynthetic pathway, the purine, pyrimidine de novo synthesis and salvage and interconversion routes, were significantly upregulated. Chemical space studied through metabolomic analysis, showed increased presence of nitrogenous compounds in extracts from induced bacteria. The metabolites orotic acid and L-phenylalaninamide were tested against R. solanacearum, E. coli, Staphylococcus sp. and B. subtilis, and exhibited activity against pathogens only in the presence of TTC, suggesting a biotransformation of nitrogenous compounds in Bacillus sp. cells as the plausible cause of the inducible antagonistic behavior.
Nanosized Alumina Particle and Proteasome Inhibitor Bortezomib Prevented inflammation and Osteolysis Induced by Titanium Particle via Autophagy and NF-κB Signaling
Authors: Zhang Zhiwei , Fu Xuewei , Xu Ling , Hu Xiaolei , Deng Feng , Yang Zhiqiang , Jiang Lin , Fu Tiwei , Zhou Pengfei , Song Jinlin , Ji Ping , Huang Jiao , Wu Xiaomian
Published: March 2020

Autophagy and NF-κB signaling are involving in the process of Particle Disease, which was caused by the particles released from friction interface of artificial joint, implant materials of particle reinforced composite, scaffolds for tissue engineering, or material for drug delivery. However, the biological interaction of different material particles and the mechanism of proteasome inhibitor, Bortezomib (BTZ), against Titanium (Ti) particle-induced Particle Disease remain unclear. In this study, we evaluated effect of nanosized Alumina (Al) particles and BTZ on reducing and treating the Ti particle-induced inflammatory reaction in MG-63 cells and mouse calvarial osteolysis model. We found that Al particles and BTZ could block apoptosis and NF- κB activation in osteoblasts in vitro and in a mouse model of calvarial resorption induced by Ti particles. We found that Al particles and BTZ attenuated the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α). And Al prevented the IL-1β expression induced by Ti via attenuating the NF- κB activation β-TRCP and reducing the expression of Casepase-3. Expressions of autophagy marker LC3 was activated in Ti group, and reduced by Al and/not BTZ. Furthermore, the expressions of OPG were also higher in these groups than the Ti treated group. Collectively, nanosized Al could prevent autophagy and reduce the apoptosis, inflammatory and osteolysis induced by Ti particles. Our data offered a basic data for implant design when it was inevitable to use Ti as biomaterials, considering the outstanding mechanical propertie of Ti. What’s more, proteasome inhibitor BTZ could be a potential therapy for wear particle-induced inflammation and osteogenic activity via regulating the activity of NF- κB signaling pathway.
The cooling mechanism of minuscule ribbed surfaces
Authors: Nishikawa M. , Otomo H. , Yoshida Y. , Deguchi J. , Tsukamoto M. , Yamamoto T.
Published: March 2020

One reason human beings wear stockings is to warm their legs. Ordinary textile materials are thermally insulative, which prevents body’s heat from dissipating. In contrary to this common sense, it was discovered that some knitted stockings made up of them permanently promote heat release and cool body. This non-intuitive phenomenon emerges when micro-size yarns are knitted to form wide spacing between neighboring yarns. However, the reason why they cool body was unclear because conventional principles of cooling garments cannot account for it. Here, in the basis of fluid-solid conjugate heat transfer analysis of natural convection, we have clarified the cooling mechanism originates from relative relationship between their geometric structure, a periodic alignment of minuscule ribs, and thermal boundary layer. Our novel finding revealed that sufficiently small ribs on the surface are exposed to steep temperature gradient within thermal boundary layer. Thereby, thermal conduction via ribs is enhanced complementarily as they are separated to guide cooler flow onto the surface. Our study provides a general insight into understanding permanent cooling mechanism on micro-size ribbed surfaces in contrast to conventional theory for heat sink, which is applicable not only to other clothes, but also to artificial devices or natural structures.
The risk of twin pregnancies should be minimized in patients with a unicornuate uterus undergoing IVF-ET
Authors: Ouyang Yan , Cai Pei , Gong Fei , Lin Ge , Qin Jiabi , Li Xihong
Published: March 2020

Unicornuate uteri are associated with infertility, miscarriage, preterm delivery and even uterine rupture. The aim of this research was to investigate the effects of unicornuate uterine anomaly on twin pregnancies after in vitro fertilization-embryo transfer (IVF-ET). A total of 206 women with unicornuate uteri (A singleton, B selective reduction (SR) of twins to a singleton, C twins) and 314 women with normal uteri (D SR of twins to a singleton, E twins) who delivered at ≥22 weeks were included. C was associated with a significantly lower live birth rate (adjusted odds ratio (aOR) 0.08, 95% confidence interval (CI), 0.01–0.69) and higher risks of preterm delivery (aOR 11.63, 95% CI, 4.85–27.92), perinatal mortality (aOR 11.43, 95% CI, 1.44–90.57) and low birth weight (aOR 5.92, 95% CI 1.94–18.06) than A, a 15-fold greater risk of preterm delivery (aOR 15.54, 95% CI 3.09–78.28) than B and a greater risk of preterm delivery (aOR 2.76, 95% CI 1.33–5.73) than E. After SR to a singleton, the perinatal outcomes were statistically similar between B and D. These results showed that the risk of twin pregnancies should be minimized in patients with unicornuate uterine anomaly undergoing IVF-ET.
Universal scaling of weak localization in graphene due to bias-induced dispersion decoherence
Authors: Somphonsane R. , Ramamoorthy H. , He G. , Nathawat J. , Yin S. , Kwan C.-P. , Arabchigavkani N. , Barut B. , Zhao M. , Jin Z. , Fransson J. , Bird J. P.
Published: March 2020

The differential conductance of graphene is shown to exhibit a zero-bias anomaly at low temperatures, arising from a suppression of the quantum corrections due to weak localization and electron interactions. A simple rescaling of these data, free of any adjustable parameters, shows that this anomaly exhibits a universal, temperature- (T) independent form. According to this, the differential conductance is approximately constant at small voltages (V < kBT/e), while at larger voltages it increases logarithmically with the applied bias. For theoretical insight into the origins of this behaviour, which is inconsistent with electron heating, we formulate a model for weak-localization in the presence of nonequilibrium transport. According to this model, the applied voltage causes unavoidable dispersion decoherence, which arises as diffusing electron partial waves, with a spread of energies defined by the value of the applied voltage, gradually decohere with one another as they diffuse through the system. The decoherence yields a universal scaling of the conductance as a function of eV/kBT, with a logarithmic variation for eV/kBT > 1, variations in accordance with the results of experiment. Our theoretical description of nonequilibrium transport in the presence of this source of decoherence exhibits strong similarities with the results of experiment, including the aforementioned rescaling of the conductance and its logarithmic variation as a function of the applied voltage.
Automated Quantification of Photoreceptor alteration in macular disease using Optical Coherence Tomography and Deep Learning
Authors: Orlando José Ignacio , Gerendas Bianca S. , Riedl Sophie , Grechenig Christoph , Breger Anna , Ehler Martin , Waldstein Sebastian M. , Bogunović Hrvoje , Schmidt-Erfurth Ursula
Published: March 2020

Diabetic macular edema (DME) and retina vein occlusion (RVO) are macular diseases in which central photoreceptors are affected due to pathological accumulation of fluid. Optical coherence tomography allows to visually assess and evaluate photoreceptor integrity, whose alteration has been observed as an important biomarker of both diseases. However, the manual quantification of this layered structure is challenging, tedious and time-consuming. In this paper we introduce a deep learning approach for automatically segmenting and characterising photoreceptor alteration. The photoreceptor layer is segmented using an ensemble of four different convolutional neural networks. En-face representations of the layer thickness are produced to characterize the photoreceptors. The pixel-wise standard deviation of the score maps produced by the individual models is also taken to indicate areas of photoreceptor abnormality or ambiguous results. Experimental results showed that our ensemble is able to produce results in pair with a human expert, outperforming each of its constitutive models. No statistically significant differences were observed between mean thickness estimates obtained from automated and manually generated annotations. Therefore, our model is able to reliable quantify photoreceptors, which can be used to improve prognosis and managment of macular diseases.
Avocado-derived polyols for use as novel co-surfactants in low energy self-emulsifying microemulsions
Authors: Ahmed Nawaz , Kermanshahi Behnoush , Ghazani Saeed M. , Tait Katrina , Tcheng Matthew , Roma Alessia , Callender Shannon P. , Smith Richard W. , Tam William , Wettig Shawn D. , Rogers Michael A. , Marangoni Alejandro G. , Spagnuolo Paul A.
Published: March 2020

Avocado (Persea americanaMill.; Lauraceae) seed-derived polyhydroxylated fatty alcohols (PFAs) or polyols (i.e., avocadene and avocadyne) are metabolic modulators that selectively induce apoptosis of leukemia stem cells and reverse pathologies associated with diet-induced obesity. Delivery systems containing avocado polyols have not been described. Herein, natural surface active properties of these polyols are characterized and incorporated into self-emulsifying drug delivery systems (SEDDS) that rely on molecular self-assembly to form fine, transparent, oil-in-water (O/W) microemulsions as small as 20 nanometers in diameter. Mechanistically, a 1:1 molar ratio of avocadene and avocadyne (i.e., avocatin B or AVO was shown to be a eutectic mixture which can be employed as a novel, bioactive, co-surfactant that significantly reduces droplet size of medium-chain triglyceride O/W emulsions stabilized with polysorbate 80.In vitrocytotoxicity of avocado polyol-SEDDS in acute myeloid leukemia cell lines indicated significant increases in potency and bioactivity compared to conventional cell culture delivery systems. A pilot pharmacokinetic evaluation of AVO SEDDS in C57BL/6J mice revealed appreciable accumulation in whole blood and biodistribution in key target tissues. Lastly, incorporation of AVO in SEDDS significantly improved encapsulation of the poorly water-soluble drugs naproxen and curcumin.
Deletion of Gpr27 in vivo reduces insulin mRNA but does not result in diabetes
Authors: Chopra Deeksha G. , Yiv Nicholas , Hennings Thomas G. , Zhang Yaohuan , Ku Gregory M.
Published: March 2020

Gpr27 is a highly conserved, orphan G protein coupled receptor (GPCR) previously implicated in pancreatic beta cell insulin transcription and glucose-stimulated insulin secretion in vitro. Here, we characterize a whole-body mouse knockout of Gpr27. Gpr27 knockout mice were born at expected Mendelian ratios and exhibited no gross abnormalities. Insulin and Pdx1 mRNA in Gpr27 knockout islets were reduced by 30%, but this did not translate to a reduction in islet insulin content or beta cell mass. Gpr27 knockout mice exhibited slightly worsened glucose tolerance with lower plasma insulin levels while maintaining similar insulin tolerance. Unexpectedly, Gpr27 deletion reduced expression of Eif4e3, a neighboring gene, likely by deleting transcription start sites on the anti-sense strand of the Gpr27 coding exon. Our data confirm that loss of Gpr27 reduces insulin mRNA in vivo but has only minor effects on glucose tolerance.
Copitarsia decolora Guenée (Lepidoptera: Noctuidae) females avoid larvae competition by detecting larvae damaged plants
Authors: Reyes-Prado Humberto , Jiménez-Pérez Alfredo , Arzuffi René , Robledo Norma
Published: March 2020

Herbivory insects can discriminate the quality of a host plant for food or oviposition, by detecting the volatile organic compounds (VOC’s) released by the plant, however, damaged plants may release a different VOC’s profile modifying the insects’ response. We tested if the VOC’s profile from damaged plants affected the response of Copitarsia decolora as these moths oviposit preferably around undamaged host plants. We assessed the response in wind tunnel conditions of C.decolora mated females to volatiles collected by dynamic headspace from 30–40 d old cabbage undamaged plants and mechanical and larval damaged plants. Headspace volatile compounds from undamaged cabbage plants were more attractive to mated females than those from larval and mechanical damaged cabbage plants. Moths stimulated with headspace volatiles from undamaged plants performed more complete flight and ovipositor displays than those moths stimulated with headspace volatiles from damaged cabbage plants. A mixture of synthetic compounds identified from undamaged cabbages elicited similar antennal and wind tunnel responses in mated females as headspace volatiles from undamaged cabbage plants. C. decolora females may discriminate between damaged and undamaged host plants by detecting their VOC’s profiles as a strategy to avoid unsuitable plants for their offspring increasing their fitness.
Towards noninvasive estimation of tumour pressure by utilising MR elastography and nonlinear biomechanical models: a simulation and phantom study
Authors: Fovargue Daniel , Fiorito Marco , Capilnasiu Adela , Nordsletten David , Lee Jack , Sinkus Ralph
Published: March 2020

The solid and fluid pressures of tumours are often elevated relative to surrounding tissue. This increased pressure is known to correlate with decreased treatment efficacy and potentially with tumour aggressiveness and therefore, accurate noninvasive estimates of tumour pressure would be of great value. We present a proof-of-concept method to infer the total tumour pressure, that is the sum of the fluid and solid parts, by examining stiffness in the peritumoural tissue with MR elastography and utilising nonlinear biomechanical models. The pressure from the tumour deforms the surrounding tissue leading to changes in stiffness. Understanding and accounting for these biases in stiffness has the potential to enable estimation of total tumour pressure. Simulations are used to validate the method with varying pressure levels, tumour shape, tumour size, and noise levels. Results show excellent matching in low noise cases and still correlate well with higher noise. Percent error remains near or below 10% for higher pressures in all noise level cases. Reconstructed pressures were also calculated from experiments with a catheter balloon embedded in a plastisol phantom at multiple inflation levels. Here the reconstructed pressures generally match the increases in pressure measured during the experiments. Percent errors between average reconstructed and measured pressures at four inflation states are 17.9%, 52%, 23.2%, and 0.9%. Future work will apply this method to in vivo data, potentially providing an important biomarker for cancer diagnosis and treatment.
Genomic Epidemiology of Vancomycin-Resistant Enterococcus faecium (VREfm) in Latin America: Revisiting The Global VRE Population Structure
Authors: Rios Rafael , Reyes Jinnethe , Carvajal Lina P. , Rincon Sandra , Panesso Diana , Echeverri Aura M. , Dinh An , Kolokotronis Sergios-Orestis , Narechania Apurva , Tran Truc T. , Munita Jose M. , Murray Barbara E. , Planet Paul J. , Arias Cesar A. , Diaz Lorena
Published: March 2020

Little is known about the population structure of vancomycin-resistant Enterococcus faecium (VREfm) in Latin America (LATAM). Here, we provide a complete genomic characterization of 55 representative Latin American VREfm recovered from 1998–2015 in 5 countries. The LATAM VREfm population is structured into two main clinical clades without geographical clustering. Using the LATAM genomes, we reconstructed the global population of VREfm by including 285 genomes from 36 countries spanning from 1946 to 2017. In contrast to previous studies, our results show an early branching of animal related isolates and a further split of clinical isolates into two sub-clades within clade A. The overall phylogenomic structure of clade A was highly dependent on recombination (54% of the genome) and the split between clades A and B was estimated to have occurred more than 2,765 years ago. Furthermore, our molecular clock calculations suggest the branching of animal isolates and clinical clades occurred ~502 years ago whereas the split within the clinical clade occurred ~302 years ago (previous studies showed a more recent split between clinical an animal branches around ~74 years ago). By including isolates from Latin America, we present novel insights into the population structure of VREfm and revisit the evolution of these pathogens.
The relationship between obstructed defecation and true rectocele in patients with pelvic organ prolapse
Authors: Tan Cheng , Geng Jing , Tang Jun , Yang Xin
Published: March 2020

We aimed to investigate the prevalence of true rectocele and obstructed defecation (OD) in patients with pelvic organ prolapse (POP), to investigate the correlation between true rectocele and OD, and to understand the diagnostic value of translabial ultrasound (TLUS) in the diagnosis of true rectocele. The patients who scheduled for POP surgery were enrolled in this study. Patients who had previous reconstructive pelvic surgery or repair of rectocele were excluded. Birmingham Bowel and Urinary symptoms questionnaires and Longo’s obstructed defecation syndrome scoring system were used to assess the bowel symptoms of patients. TLUS was used to evaluate anatomical defects. P value <0.05 was considered statistically significant, and confidence intervals were set at 95%. 279 patients were included into this study. The prevalence rate of OD was 43%, and the average value of ODS score was 6.67. 17% patients presented straining at stool, 33% presented incomplete emptying, 13% presented digitations, and 12% required laxatives or enema. The prevalence rate of true rectocele was 23%. Defecation symptoms were significantly correlated with age, levator-ani hiatus, levator-ani muscle injury and true rectocele. Logistic regression showed that true rectocele and increased levator-ani hiatus were independent risk factors of OD. True rectocele was significantly correlated with straining at stool, digitation, incomplete emptying and requirement of laxatives or enema.In POP patients, the prevalence rate of true rectocele and OD was 23% and 43%, respectively. True rectocele was related to OD. TLUS was a valuable approach in anatomical evaluation of POP.
Water-Window X-Ray Pulses from a Laser-Plasma Driven Undulator
Authors: Maier A. R. , Kajumba N. , Guggenmos A. , Werle C. , Wenz J. , Delbos N. , Zeitler B. , Dornmair I. , Schmidt J. , Gullikson E. M. , Krausz F. , Schramm U. , Kleineberg U. , Karsch S. , Grüner F.
Published: March 2020

Femtosecond (fs) x-ray pulses are a key tool to study the structure and dynamics of matter on its natural length and time scale. To complement radio-frequency accelerator-based large-scale facilities, novel laser-based mechanisms hold promise for compact laboratory-scale x-ray sources. Laser-plasma driven undulator radiation in particular offers high peak-brightness, optically synchronized few-fs pulses reaching into the few-nanometer (nm) regime. To date, however, few experiments have successfully demonstrated plasma-driven undulator radiation. Those that have, typically operated at single and comparably long wavelengths. Here we demonstrate plasma-driven undulator radiation with octave-spanning tuneability at discrete wavelengths reaching from 13 nm to 4 nm. Studying spontaneous undulator radiation is an important step towards a plasma-driven free-electron laser. Our specific setup creates a photon pulse, which closely resembles the plasma electron bunch length and charge profile and thus might enable novel methods to characterize the longitudinal electron phase space.
Robustness in spatially driven bistability in signaling systems
Authors: Tenenbaum Debora , Marrone Juan Ignacio , Grecco Hernán E. , Ventura Alejandra C.
Published: March 2020

Biological systems are spatially organized. This microscopic heterogeneity has been shown to produce emergent complex behaviors such as bistability. Even though the connection between spatiality and dynamic response is essential to understand biological output, its robustness and extent has not been sufficiently explored. This work focuses on a previously described system which is composed of two monostable modules acting on different cellular compartments and sharing species through linear shuttling reactions. One of the two main purposes of this paper is to quantify the frequency of occurrence of bistability throughout the parameter space and to identify which parameters and in which value ranges control the emergence and the properties of bistability. We found that a very small fraction of the sampled parameter space produced a bistable response. Most importantly, shuttling parameters were among the most influential ones to control this property. The other goal of this paper is to simplify the same system as much as possible without losing compartment-induced bistability. This procedure provided a simplified model that still connects two monostable systems by a reduced set of linear shuttling reactions that circulates all the species around the two compartments. Bistable systems are one of the main building blocks of more complex behaviors such as oscillations, memory, and digitalization. Therefore, we expect that the proposed minimal system provides insight into how these behaviors can arise from compartmentalization.
Transcriptomics in cancer revealed by Positron Emission Tomography radiomics
Authors: Tixier Florent , Cheze-le-Rest Catherine , Schick Ulrike , Simon Brigitte , Dufour Xavier , Key Stéphane , Pradier Olivier , Aubry Marc , Hatt Mathieu , Corcos Laurent , Visvikis Dimitris
Published: March 2020

Metabolic images from Positron Emission Tomography (PET) are used routinely for diagnosis, follow-up or treatment planning purposes of cancer patients. In this study we aimed at determining if radiomic features extracted from18F-Fluoro Deoxy Glucose (FDG) PET images could mirror tumor transcriptomics. In this study we analyzed 45 patients with locally advanced head and neck cancer (H&N) that underwent FDG-PET scans at the time of diagnosis and transcriptome analysis using RNAs from both cancer and healthy tissues on microarrays. Association between PET radiomics and transcriptomics was carried out with the Genomica software and a functional annotation was used to associate PET radiomics, gene expression and altered biological pathways. We identified relationships between PET radiomics and genes involved in cell-cycle, disease, DNA repair, extracellular matrix organization, immune system, metabolism or signal transduction pathways, according to the Reactome classification. Our results suggest that these FDG PET radiomic features could be used to infer tissue gene expression and cellular pathway activity in H&N cancers. These observations strengthen the value of radiomics as a promising approach to personalize treatments through targeting tumor-specific molecular processes.
Exploring a Path Model of Cognitive Impairment, Functional Disability, and Incontinence Among Male Veteran Home Residents in Southern Taiwan
Authors: Su Yung-Yu , Tsai Ying-Yi , Chu Chiao-Lee , Lin Chien-Chih , Chen Chun-Min
Published: March 2020

Most studies focusing on only one directional effect among cognitive health, physical function, and incontinence may miss potential paths. This study aimed to determine the pathway by analyzing the bidirectional effects of exposure (X) on outcome (Y) and explore the mediating effect (M) between X and Y. Secondary data analyses were performed in this study. The original data were collected from August to October 2013 in one VH in Tainan, Taiwan, and the final sample size was 144 older male veterans. Path analysis was performed to test the pathway sequence X → M → Y among the three outcome variables. Approximately 80% of the veterans were aged 81 or older, approximately 42% had a functional disability, 26% had cognitive impairment, and 20% had incontinence. The relationships between functional disability and incontinence and between functional disability and cognition impairment were bidirectional, and functional disability played a key mediating role in the relationship between cognitive impairment and incontinence. Physical more than cognitive training in order to improve or at least stabilize functional performance could be a way to prevent or reduce the process of developing incontinence.
Specific gene expression in type 1 diabetic patients with and without cardiac autonomic neuropathy
Authors: Gastol Joanna , Polus Anna , Biela Maria , Razny Urszula , Pawlinski Lukasz , Solnica Bogdan , Kiec-Wilk Beata
Published: March 2020

We hypothesized that some molecular pathways might interact to initiate the process of nervous tissue destruction, promoting cardiac autonomic neuropathy (CAN) in the course of diabetes type 1 (T1D). The study group consisted of 60 T1D patients (58.33% women/41.67% men), on standard therapy. The control group consisted of twenty healthy volunteers recruited in accordance with age, gender and body weight. The presence of CAN was documented by the Ewing test method (ProSciCard apparatus). A microarray data analysis was performed using Gene Spring version 13. The microarray results for selected genes were confirmed by real-time PCR (qRT-PCR), using specific TaqMan Gene Expression Assays. Plasma IL‐6 content was measured by an enzyme-linked immunosorbent assay (ELISA). The p < 0.05 value was considered as statistically significant. The microarray analysis, confirmed by qRTPCR, showed significant up-regulation of autophagy, quantity of mitochondria, quality regulatory genes (mTOR, GABARAPL2) apoptosis, ER-stress and inflammation (NFKB1, IL1b, IL1R1, SOD1), in T1D when compared to the control group. A significantly higher IL-6 protein level was observed in T1D patients, in comparison to the control group. We concluded that the observed changes in gene expression and activation of intracellular pathways give a coherent picture of the important role of oxidative stress in inflammation and the activation of apoptosis in the pathomechanism of DM. The significance of the inflammatory process, confirmed by the increased level of the inflammation biomarker IL-6 in the pathomechanisms of CAN was shown even in patients with properly treated T1D.