bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supramolecular peptide constructed by molecular Lego allowing programmable self-assembly for photodynamic therapy
Authors: Zhu Huangtianzhi , Wang Huanhuan , Shi Bingbing , Shangguan Liqing , Tong Weijun , Yu Guocan , Mao Zhengwei , Huang Feihe 
Published: June 2019

AbstractPeptide self-assemblies with multiple nanostructures have great potentials in functional biomaterials, and yet the tedious and costly covalent peptide modification and the lack of facile controllability on self-assembly morphology retard the peptide-related exploration. Here we report a simple approach to fabricate a supramolecular peptide that shows programmable self-assembly with multiple morphologies and application in photodynamic therapy. Pillar[5]arene-based host−guest recognition is used to construct a supramolecular peptide, which simplify the peptide modification and promote the controllability of the self-assembly behavior. Due to the ERGDS sequences on the exterior surfaces and hydrophobic cores of self-assemblies, the nanoparticles formed from the supramolecular peptide are suitable vehicles to encapsulate a photosensitizer for photodynamic therapy. In vitro and in vivo studies demonstrate that the inherent targeting capability and supramolecular strategy greatly boost its photodynamic therapeutic efficiency. This supramolecular peptide holds promising potentials in precise cancer therapy and perspectives for the peptide modification.
Structural basis for the clamping and Ca2+ activation of SNARE-mediated fusion by synaptotagmin
Authors: Grushin Kirill , Wang Jing , Coleman Jeff , Rothman James E. , Sindelar Charles V. , Krishnakumar Shyam S. 
Published: June 2019

AbstractSynapotagmin-1 (Syt1) interacts with both SNARE proteins and lipid membranes to synchronize neurotransmitter release to calcium (Ca2+) influx. Here we report the cryo-electron microscopy structure of the Syt1–SNARE complex on anionic-lipid containing membranes. Under resting conditions, the Syt1 C2 domains bind the membrane with a magnesium (Mg2+)-mediated partial insertion of the aliphatic loops, alongside weak interactions with the anionic lipid headgroups. The C2B domain concurrently interacts the SNARE bundle via the ‘primary’ interface and is positioned between the SNAREpins and the membrane. In this configuration, Syt1 is projected to sterically delay the complete assembly of the associated SNAREpins and thus, contribute to clamping fusion. This Syt1–SNARE organization is disrupted upon Ca2+-influx as Syt1 reorients into the membrane, likely displacing the attached SNAREpins and reversing the fusion clamp. We thus conclude that the cation (Mg2+/Ca2+) dependent membrane interaction is a key determinant of the dual clamp/activator function of Synaptotagmin-1.
Highly stacked 3D organic integrated circuits with via-hole-less multilevel metal interconnects
Authors: Yoo Hocheon , Park Hongkeun , Yoo Seunghyun , On Sungmin , Seong Hyejeong , Im Sung Gap , Kim Jae-Joon 
Published: June 2019

AbstractMultilevel metal interconnects are crucial for the development of large-scale organic integrated circuits. In particular, three-dimensional integrated circuits require a large number of vertical interconnects between layers. Here, we present a novel multilevel metal interconnect scheme that involves solvent-free patterning of insulator layers to form an interconnecting area that ensures a reliable electrical connection between two metals in different layers. Using a highly reliable interconnect method, the highest stacked organic transistors to date, a three-dimensional organic integrated circuits consisting of 5 transistors and 20 metal layers, is successfully fabricated in a solvent-free manner. All transistors exhibit outstanding device characteristics, including a high on/off current ratio of ~107, no hysteresis behavior, and excellent device-to-device uniformity. We also demonstrate two vertically-stacked complementary inverter circuits that use transistors on 4 different floors. All circuits show superb inverter characteristics with a 100% output voltage swing and gain up to 35 V per V.
Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma
Authors: Maximov Victor , Chen Zhihong , Wei Yun , Robinson M. Hope , Herting Cameron J. , Shanmugam Nithya S. , Rudneva Vasilisa A. , Goldsmith Kelly C. , MacDonald Tobey J. , Northcott Paul A. , Hambardzumyan Dolores , Kenney Anna M. 
Published: June 2019

AbstractMedulloblastoma, which is the most common malignant paediatric brain tumour, has a 70% survival rate, but standard treatments often lead to devastating life-long side effects and recurrence is fatal. One of the emerging strategies in the search for treatments is to determine the roles of tumour microenvironment cells in the growth and maintenance of tumours. The most attractive target is tumour-associated macrophages (TAMs), which are abundantly present in the Sonic Hedgehog (SHH) subgroup of medulloblastoma. Here, we report an unexpected beneficial role of TAMs in SHH medulloblastoma. In human patients, decreased macrophage number is correlated with significantly poorer outcome. We confirm macrophage anti-tumoural behaviour in both ex vivo and in vivo murine models of SHH medulloblastoma. Taken together, our findings suggest that macrophages play a positive role by impairing tumour growth in medulloblastoma, in contrast to the pro-tumoural role played by TAMs in glioblastoma, another common brain tumour.
Contact patterning by laser printing for flexible electronics on paper
Authors: Harper Angela F. , Diemer Peter J. , Jurchescu Oana D. 
Published: June 2019

AbstractThe desire for cost-effective strategies for producing organic electronic devices has led to many new methods for the organic semiconductor layer deposition; however, manufacturing contacts remains an expensive technique due to the high cost of both the materials used and the processing necessary for their patterning. In this work, we present a method for contact deposition and patterning, which overcomes these limitations and allows fabrication of all-printed organic thin-film transistors on paper. The method relies on depositing contacts using aerosol spray and patterning them with a digitally printed mask from an office laser printer, at ambient temperature and pressure. This technique, which we have denoted aerosol spray laser lithography, is cost-effective and extremely versatile in terms of material choice and electrode geometry. As the processing temperature does not exceed 155 °C, it is compatible with a variety of substrates, including plastic or paper. The success of this method marks an opportunity for a rapid, scalable, and low-cost alternative to current electrode-manufacturing techniques for development of flexible, large-area, electronic applications.
Suppression of olfactory signal transduction by insecticides
Authors: Takeuchi Hiroko , Kurahashi Takashi 
Published: June 2019

Abstract2,4,6-Trichloroanisole (TCA) is a well-known, potent off-flavour compound present in various foods and beverages. TCA has been hypothesised to be a universal cause of flavour loss experienced in daily life. Here, however, we show that titres for the suppression of olfactory transducer channels caused by low-quality bananas are much higher than those for that caused by the TCA itself contained in the banana. We resurveyed other components of low-quality bananas and found that bananas also contain an insecticide (chlorpyrifos), and that it suppresses olfactory transducer channels. Other insecticides also suppressed olfactory transducer channels. Hence, even after passing safety examinations, certain insecticides may decrease the quality of foods and beverages by reducing their intrinsic scents.
HIV therapeutic vaccine enhances non-exhausted CD4+ T cells in a randomised phase 2 trial
Authors: Vieillard Vincent , Combadière Béhazine , Tubiana Roland , Launay Odile , Pialoux Gilles , Cotte Laurent , Girard Pierre-Marie , Simon Anne , Dudoit Yasmine , Reynes Jacques , Rockstroh Jürgen , Garcia Felipe , Gatell Jose , Devidas Alain , Yazdanpanah Yazdan , Weiss Laurence , Fätkenheuer Gerd , Autran Brigitte , Joyeux Delphine , Gharakhanian Shahin , Debré Patrice , Katlama Christine 
Published: June 2019

AbstractVAC-3S is a therapeutic vaccine comprising a highly conserved HIV-gp41 motif coupled with the CRM197 carrier protein. High levels of anti-3S antibodies (Abs) have been associated with improved protection of CD4+ T-cell survival. A previous phase 1 study demonstrated the safety of VAC-3S. This multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial enroled between January 2014 and March 2015 HIV-1-infected patients under ART with plasma HIV RNA levels below 50 copies/mL and CD4 counts between 200 and 500 cells/μL. Participants were immunised with 16, 32, or 64 μg of VAC-3S, and compared to placebo. The primary outcome was immunogenicity assessed by changes from baseline of anti-3S Abs levels at week 12. Secondary outcomes included adverse events and the course of plasma HIV RNA level, CD4 count, CD4/CD8 ratio, inflammation and immune checkpoints from week 0 to week 48. Vaccination was well tolerated with no serious adverse events and induced a significant increase in anti-3S Ab response in vaccinated patients (p < 0.0001), compared to placebo. In high responders, the robust increased of CD4 count was associated with a significant and sustained reduction of PD-1 expression on CD4+ T cells through week 48 (variance p = 0.0017). PD-1 expression was correlated with level of anti-3S Abs (p = 0.0092, r = −0.68) and expression of NKp44L (p < 0.0001; r = 0.54) in CD4+ T cells. Our findings regarding the increase of non-exhausted CD4+ T cells have potentially important application in personalised HIV vaccination for HIV-infected patients with high level of PD-1 to improve their T-cell immune function.
Synergistic effect of band convergence and carrier transport on enhancing the thermoelectric performance of Ga doped Cu2Te at medium temperatures
Authors: Sarkar Sayan , Sarswat Prashant K. , Saini Shrikant , Mele Paolo , Free Michael L. 
Published: June 2019

AbstractRecent advances in high performance thermoelectric materials have garnered unprecedented attention owing to their capability of direct transformation of heat energy to useful electricity. Copper Telluride (Cu2Te), a member of the chalcogenide family has emerged as a state-of-the-art thermoelectric material with low thermal conductivity and high thermoelectric (TE) performance, however, this material exhibits exceptional transport properties only at very high temperatures. In this study, we have investigated the synergistic effects of Ga doping on the TE performance by first principles calculations along with experimental validations. The DFT (Density Functional Theory) calculations predicted that Ga doping, within considerable limits enhanced the electrical conductivity and Seebeck coefficients in Cu2Te. This proof of concept was validated by experimental synthesis of Ga doped Cu2Te by simple direct annealing for shorter durations of 48 hours at 1120 ºC (~1/4th) than in previous work and subsequent thermoelectric characterization. The enhanced electrical conductivity, thermopower, and moderate thermal conductivities led to the optimized TE performance in 3 atomic % Ga doping (Cu1.97Ga0.03Te), exhibiting a ZT value of 0.46 at 600 K, almost three times that of pristine Cu2Te in this temperature range. This comprehensive study provides the platform for developing new low-cost and energy efficient TE materials with enhanced ZT performance in medium temperature applications.
Fast eating is a strong risk factor for new-onset diabetes among the Japanese general population
Authors: Kudo Akihiro , Asahi Koichi , Satoh Hiroaki , Iseki Kunitoshi , Moriyama Toshiki , Yamagata Kunihiro , Tsuruya Kazuhiko , Fujimoto Shouichi , Narita Ichiei , Konta Tsuneo , Kondo Masahide , Shibagaki Yugo , Kasahara Masato , Watanabe Tsuyoshi , Shimabukuro Michio 
Published: June 2019

AbstractAlthough many studies that have examined the relationship of type and amount of food and the frequency of eating with new onset of diabetes, there are few reports on the relationship between how meals are eaten, such as skipping breakfast, snacking or food ingestion speed, and the onset of diabetes. We investigated the relationship between eating speed, as well as other eating habits such as snacking and skip breakfast, and new onset of diabetes in a nation-wide Japanese cohort. We obtained data from the nation-wide annual health check program in Japan. In 197,825 participants without diabetes in 2008, questionnaires recorded data on the diet habits (eating speed, snack after supper or before sleep, and skipping breakfast) and unadjusted and multivariable-adjusted logistic regression models were used to measure the odds ratio of new-onset diabetes mellitus in a 3-year follow up. The proportion of fast eaters, those who snack after supper, snack before sleep, and skip breakfast was higher in the new-onset diabetes group than in the group who did not develop diabetes mellitus. As compared with the non-fast eater group, fast eaters were generally younger, had higher BMI, had more weight gain from 20 years onwards, and experienced frequent weight fluctuations of ≥3 kg within 1 year. The risk of fast eaters developing diabetes mellitus remained even after correction for multiple factors including age, body weight, rate of weight change, blood pressure, smoking, and alcohol consumption. No other eating habits were independent predictors for onset of diabetes mellitus. Results show that fast eating is a sole predisposing factor among eating habits for new-onset diabetes. Future studies were warranted to evaluate whether avoidance of fast eating is beneficial for prevention of diabetes mellitus.
Non-Invasive Photodynamic Therapy against -Periodontitis-causing Bacteria
Authors: Park Danbi , Choi Eun Joo , Weon Kwon-Yeon , Lee Wan , Lee Seoung Hoon , Choi Joon-Seok , Park Gyu Hwan , Lee Bada , Byun Mi Ran , Baek Kyunghwa , Choi Jin Woo 
Published: June 2019

AbstractPeriodontitis is initiated by causative bacteria in the gingival sulcus. However, as the lesion is often deep and out of circulation system and biofilm is frequently formed on the bacteria cluster, use of antibacterial agents has been limited and the invasive method such as curettage is thought as an only treatment. Here we designed non-invasive photodynamic therapy (PDT), with the ointment which leads a photosensitizer deliverable into gingival sulcus. We assessed whether 650 nm light-emitting-diode (LED) penetrates the 3-mm soft tissue and effectively activates a photosensitizer toluidine-blue-O (TBO) through the thickness to remove Porphyromonas gingivalis and Fusobacterium nucleatum species. The oral ointment formulation was optimized to efficiently deliver the photosensitizer into gingival sulcus and its efficacy of PDT was evaluated in in vitro and in vivo models. Four weeks of TBO-formulation mediated-PDT treatment significantly attenuated periodontitis-induced alveolar bone loss and inflammatory cytokines production in rats. These results confirm that a 650 nm LED indeed penetrates the gingiva and activates our TBO formulation which is sufficiently delivered to, and retained within, the gingival sulcus; thus, it effectively kills the bacteria that reside around the gingival sulcus. Collectively, TBO-mediated PDT using LED irradiation has potential as a safe adjunctive procedure for periodontitis treatment.
Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure
Authors: Younge Noelle E. , Newgard Christopher B. , Cotten C. Michael , Goldberg Ronald N. , Muehlbauer Michael J. , Bain James R. , Stevens Robert D. , O’Connell Thomas M. , Rawls John F. , Seed Patrick C. , Ashley Patricia L. 
Published: June 2019

AbstractGrowth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention.
Functional characterisation of a novel class of in-frame insertion variants of KRAS and HRAS
Authors: Eijkelenboom Astrid , van Schaik Frederik M. A. , van Es Robert M. , Ten Broek Roel W. , Rinne Tuula , van der Vleuten Carine , Flucke Uta , Ligtenberg Marjolijn J. L. , Rehmann Holger 
Published: June 2019

AbstractMutations in the RAS genes are identified in a variety of clinical settings, ranging from somatic mutations in oncology to germline mutations in developmental disorders, also known as ‘RASopathies’, and vascular malformations/overgrowth syndromes. Generally single amino acid substitutions are identified, that result in an increase of the GTP bound fraction of the RAS proteins causing constitutive signalling. Here, a series of 7 in-frame insertions and duplications in HRAS (n = 5) and KRAS (n = 2) is presented, resulting in the insertion of 7–10 amino acids residues in the switch II region. These variants were identified in routine diagnostic screening of 299 samples for somatic mutations in vascular malformations/overgrowth syndromes (n = 6) and in germline analyses for RASopathies (n = 1). Biophysical characterization shows the inability of Guanine Nucleotide Exchange Factors to induce GTP loading and reduced intrinsic and GAP-stimulated GTP hydrolysis. As a consequence of these opposing effects, increased RAS signalling is detected in a cellular model system. Therefore these in-frame insertions represent a new class of weakly activating clinically relevant RAS variants.
Microfluidic Collective Cell Migration Assay for Study of Endothelial Cell Proliferation and Migration under Combinations of Oxygen Gradients, Tensions, and Drug Treatments
Authors: Shih Hsiu-Chen , Lee Tse-Ang , Wu Hsiao-Mei , Ko Ping-Liang , Liao Wei-Hao , Tung Yi-Chung 
Published: June 2019

AbstractProliferation and migration of endothelial cells play an important role in many biological activities, and they can be regulated by various microenvironmental factors. In this paper, a novel microfluidic collective cell migration assay is developed to study endothelial cell migration and proliferation under combinations of three oxygen conditions: normoxia, oxygen gradient, and hypoxia and three medium compositions: normal growth medium, the medium with cytochalasin-D for actin polymerization inhibition, and with YC-1 for hypoxia-inducible factor (HIF) inhibition. The microfluidic device designed in the paper allows cell patterns formed with consistent dimensions using laminar flow patterning. In addition, stable oxygen gradients can be generated within the device by a spatially confined chemical reaction method. The device can be operated in conventional cell incubators with minimal chemical reagents and instrumentation for practical applications. The results show directional collective cell migration of the endothelial cells under the oxygen gradients for all the medium compositions. The directional behavior has never been discussed before, and indicates critical roles of oxygen gradients in guiding endothelial cell migration during various biological activities. The developed assay provides a practical yet powerful tool for further in vitro study of endothelial cell behaviors under various physiological microenvironments.
A critical analysis of Powell’s results on the interdivision time distribution
Authors: Quedeville Vincent , Morchain Jérôme , Villedieu Philippe , Fox Rodney O. 
Published: June 2019

AbstractThe cell-age and interdivision-time probability density functions (PDFs) have been extensively investigated since the 1940s due to their fundamental role in cell growth. The pioneering work of Powell established the first relationship between the interdivision-time and cell-age PDFs. In the literature, two definitions for the interdivision-time PDF have been proposed. One stands for the age-at-rupture PDF and is experimentally observable, whereas the other is the probability density that a cell divides at a certain age and is unobservable. From Powell’s results pertaining to the unobservable interdivision-time PDF, Painter and Marr derived an inequality that is true but is incorrectly used by experimentalists to analyse single-cell data. Unfortunately, the confusion between these two PDFs persists. To dissipate this confusion, exact relationships between the cell-age and the interdivision-time PDFs are derived in this work from an age-structured model, which can be used by experimentalists to analyse cell growth in batch and continuous culture modes.
Dietary Patterns and Age-Related Macular Degeneration in Korea: The Korea National Health and Nutrition Examination Survey 2010–2011
Authors: Kang Kyung Tae , Kim Yu Cheol 
Published: June 2019

AbstractThis study was performed to reveal dietary patterns and age-related macular degeneration risk association in general Korean population. A retrospective cross-sectional database analysis using the data collected from January 2010 to December 2011 at a Korea nationwide survey was conducted. The present analysis was performed from December 2016 to November 2017. Detailed grading with fundus photographs was performed by observers blinded to the patient characteristics. The current study focused on subjects forty year and older who had fundus photographs that is assessable from at least one eye (7,899 participants). Participants were excluded if they reported extreme energy intake (142 participants) or if they were likely to have changed dietary behavior (1,171 participants), or with missing data (n = 764). After exclusion, 5,843 participants data were analyzed in the current study. As the result, 6.8% of the participants exhibited early stages of age-related macular degeneration and 0.6% exhibited late stages. Furthermore, relatively more frequent fish consumption was associated reduced odds of early age-related macular degeneration when comparing the third quartile with the first quartile groups, however, relatively more frequent legume consumption was associated with reduced odds of late age-related macular degeneration when comparing the third quartile with the first quartile groups. In conclusion, the current study insists that the diet pattern rich in fish and legume might have protective effect against age-related macular degeneration in Korean population.