bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmaceutical concentration using organic solvent forward osmosis for solvent recovery
Authors: Cui Yue , Chung Tai-Shung 
Published: April 2018

AbstractThe organic solvent forward osmosis (OSFO) process can simultaneously concentrate the active pharmaceutical ingredients (APIs) and recover the organic solvents. Here we demonstrate and evaluate an OSFO process for solvent recovery. In this demonstration, OSFO was conducted in different solvents with different draw solutes. The OSFO process shows rejections >98% when recovering organic solvents from different feed solutions, even when the feed concentration is as high as 20 wt%. More importantly, all systems exhibit relatively low ratios of reverse solute flux to solvent flux, indicating that the adverse effects of using hazardous draw solutions could be minimized. Nevertheless, the use of non-hazardous draw solutes such as citric acid is highly recommended to remove any potential risk, and it has been demonstrated. Herein, the OSFO process is a promising technology for solvent recovery as it possesses a reasonable solvent flux, low reverse solute flux and requires no external pressure.
Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement
Authors: Orengo J. M. , Radin A. R. , Kamat V. , Badithe A. , Ben L. H. , Bennett B. L. , Zhong S. , Birchard D. , Limnander A. , Rafique A. , Bautista J. , Kostic A. , Newell D. , Duan X. , Franklin M. C. , Olson W. , Huang T. , Gandhi N. A. , Lipsich L. , Stahl N. , Papadopoulos N. J. , Murphy A. J. , Yancopoulos G. D. 
Published: April 2018

AbstractAcute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.
Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X chromosome
Authors: Bonora G. , Deng X. , Fang H. , Ramani V. , Qiu R. , Berletch J. B. , Filippova G. N. , Duan Z. , Shendure J. , Noble W. S. , Disteche C. M. 
Published: April 2018

AbstractThe mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. Using Hi-C in edited mouse cells with allelic deletions or inversions within the hinge, here we show that the conserved Dxz4 locus is necessary to maintain this bipartite structure. Dxz4 orientation controls the distribution of contacts on the Xi, as shown by a massive reversal in long-range contacts after Dxz4 inversion. Despite an increase in CTCF binding and chromatin accessibility on the Xi in Dxz4-edited cells, only minor changes in TAD structure and gene expression were detected, in accordance with multiple epigenetic mechanisms ensuring X silencing. We propose that Dxz4 represents a structural platform for frequent long-range contacts with multiple loci in a direction dictated by the orientation of its bank of CTCF motifs, which may work as a ratchet to form the distinctive bipartite structure of the condensed Xi.
Characterising the phenotypic evolution of circulating tumour cells during treatment
Authors: Tsao Simon Chang-Hao , Wang Jing , Wang Yuling , Behren Andreas , Cebon Jonathan , Trau Matt 
Published: April 2018

AbstractReal-time monitoring of cancer cells’ phenotypic evolution during therapy can provide vital tumour biology information for treatment management. Circulating tumour cell (CTC) analysis has emerged as a useful monitoring tool, but its routine usage is restricted by either limited multiplexing capability or sensitivity. Here, we demonstrate the use of antibody-conjugated and Raman reporter-coated gold nanoparticles for simultaneous labelling and monitoring of multiple CTC surface markers (named as “cell signature”), without the need for isolating individual CTCs. We observe cell heterogeneity and phenotypic changes of melanoma cell lines during molecular targeted treatment. Furthermore, we follow the CTC signature changes of 10 stage-IV melanoma patients receiving immunological or molecular targeted therapies. Our technique maps the phenotypic evolution of patient CTCs sensitively and rapidly, and shows drug-resistant clones having different CTC signatures of potential clinical value. We believe our proposed method is of general interest in the CTC relevant research and translation fields.
Chirality-controlled crystallization via screw dislocations
Authors: Sung Baeckkyoung , de la Cotte Alexis , Grelet Eric 
Published: April 2018

AbstractChirality plays an important role in science from enantiomeric separation in chemistry to chiral plasmonics in nanotechnology. However, the understanding of chirality amplification from chiral building blocks to ordered helical superstructures remains a challenge. Here, we demonstrate that topological defects, such as screw dislocations, can drive the chirality transfer from particle to supramolecular structure level during the crystallization process. By using a model system of chiral particles, which enables direct imaging of single particle incorporation into growing crystals, we show that the crystallization kinetic pathway is the key parameter for monitoring, via the defects, the chirality amplification of the crystalline structures from racemic to predominantly homohelical. We provide an explanation based on the interplay between geometrical frustration, racemization induced by thermal fluctuations, and particle chirality. Our results demonstrate that screw dislocations not only promote the growth, but also control the chiral morphology and therefore the functionality of crystalline states.
Rapid increase in atmospheric iodine levels in the North Atlantic since the mid-20th century
Authors: Cuevas Carlos A. , Maffezzoli Niccolò , Corella Juan Pablo , Spolaor Andrea , Vallelonga Paul , Kjær Helle A. , Simonsen Marius , Winstrup Mai , Vinther Bo , Horvat Christopher , Fernandez Rafael P. , Kinnison Douglas , Lamarque Jean-François , Barbante Carlo , Saiz-Lopez Alfonso 
Published: April 2018

AbstractAtmospheric iodine causes tropospheric ozone depletion and aerosol formation, both of which have significant climate impacts, and is an essential dietary element for humans. However, the evolution of atmospheric iodine levels at decadal and centennial scales is unknown. Here, we report iodine concentrations in the RECAP ice-core (coastal East Greenland) to investigate how atmospheric iodine levels in the North Atlantic have evolved over the past 260 years (1750–2011), this being the longest record of atmospheric iodine in the Northern Hemisphere. The levels of iodine tripled from 1950 to 2010. Our results suggest that this increase is driven by anthropogenic ozone pollution and enhanced sub-ice phytoplankton production associated with the recent thinning of Arctic sea ice. Increasing atmospheric iodine has accelerated ozone loss and has considerably enhanced iodine transport and deposition to the Northern Hemisphere continents. Future climate and anthropogenic forcing may continue to amplify oceanic iodine emissions with potentially significant health and environmental impacts at global scale.
AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus
Authors: Ando Fumiaki , Mori Shuichi , Yui Naofumi , Morimoto Tetsuji , Nomura Naohiro , Sohara Eisei , Rai Tatemitsu , Sasaki Sei , Kondo Yoshiaki , Kagechika Hiroyuki , Uchida Shinichi 
Published: April 2018

AbstractCongenital nephrogenic diabetes insipidus (NDI) is characterized by the inability of the kidney to concentrate urine. Congenital NDI is mainly caused by loss-of-function mutations in the vasopressin type 2 receptor (V2R), leading to impaired aquaporin-2 (AQP2) water channel activity. So far, treatment options of congenital NDI either by rescuing mutant V2R with chemical chaperones or by elevating cyclic adenosine monophosphate (cAMP) levels have failed to yield effective therapies. Here we show that inhibition of A-kinase anchoring proteins (AKAPs) binding to PKA increases PKA activity and activates AQP2 channels in cortical collecting duct cells. In vivo, the low molecular weight compound 3,3′-diamino-4,4′-dihydroxydiphenylmethane (FMP-API-1) and its derivatives increase AQP2 activity to the same extent as vasopressin, and increase urine osmolality in the context of V2R inhibition. We therefore suggest that FMP-API-1 may constitute a promising lead compound for the treatment of congenital NDI caused by V2R mutations.
Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections
Authors: Early Angela M. , Lievens Marc , MacInnis Bronwyn L. , Ockenhouse Christian F. , Volkman Sarah K. , Adjei Samuel , Agbenyega Tsiri , Ansong Daniel , Gondi Stacey , Greenwood Brian , Hamel Mary , Odero Chris , Otieno Kephas , Otieno Walter , Owusu-Agyei Seth , Asante Kwaku Poku , Sorgho Hermann , Tina Lucas , Tinto Halidou , Valea Innocent , Wirth Dyann F. , Neafsey Daniel E. 
Published: April 2018

AbstractHost immunity exerts strong selective pressure on pathogens. Population-level genetic analysis can identify signatures of this selection, but these signatures reflect the net selective effect of all hosts and vectors in a population. In contrast, analysis of pathogen diversity within hosts provides information on individual, host-specific selection pressures. Here, we combine these complementary approaches in an analysis of the malaria parasitePlasmodium falciparumusing haplotype sequences from thousands of natural infections in sub-Saharan Africa. We find that parasite genotypes show preferential clustering within multi-strain infections in young children, and identify individual amino acid positions that may contribute to strain-specific immunity. Our results demonstrate that natural host defenses toP. falciparumact in an allele-specific manner to block specific parasite haplotypes from establishing blood-stage infections. This selection partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines targeting such proteins should account for allele-specific immunity.
Horn-like space-coiling metamaterials toward simultaneous phase and amplitude modulation
Authors: Ghaffarivardavagh Reza , Nikolajczyk Jacob , Glynn Holt R. , Anderson Stephan , Zhang Xin 
Published: April 2018

AbstractAcoustic metasurfaces represent a family of planar wavefront-shaping devices garnering increasing attention due to their capacity for novel acoustic wave manipulation. By precisely tailoring the geometry of these engineered surfaces, the effective refractive index may be modulated and, consequently, acoustic phase delays tuned. Despite the successful demonstration of phase engineering using metasurfaces, amplitude modulation remains overlooked. Herein, we present a class of metasurfaces featuring a horn-like space-coiling structure, enabling acoustic control with simultaneous phase and amplitude modulation. The functionality of this class of metasurfaces, featuring a gradient in channel spacing, has been investigated theoretically and numerically and an equivalent model simplifying the structural behavior is presented. A metasurface featuring this geometry has been designed and its functionality in modifying acoustic radiation patterns experimentally validated. This class of acoustic metasurface provides an efficient design methodology enabling complete acoustic wave manipulation, which may find utility in applications including biomedical imaging, acoustic communication, and non-destructive testing.
Unifying the global phylogeny and environmental distribution of ammonia-oxidising archaea based on amoA genes
Authors: Alves Ricardo J. Eloy , Minh Bui Quang , Urich Tim , von Haeseler Arndt , Schleper Christa 
Published: April 2018

AbstractAmmonia-oxidising archaea (AOA) are ubiquitous and abundant in nature and play a major role in nitrogen cycling. AOA have been studied intensively based on the amoA gene (encoding ammonia monooxygenase subunit A), making it the most sequenced functional marker gene. Here, based on extensive phylogenetic and meta-data analyses of 33,378 curated archaeal amoA sequences, we define a highly resolved taxonomy and uncover global environmental patterns that challenge many earlier generalisations. Particularly, we show: (i) the global frequency of AOA is extremely uneven, with few clades dominating AOA diversity in most ecosystems; (ii) characterised AOA do not represent most predominant clades in nature, including soils and oceans; (iii) the functional role of the most prevalent environmental AOA clade remains unclear; and (iv) AOA harbour molecular signatures that possibly reflect phenotypic traits. Our work synthesises information from a decade of research and provides the first integrative framework to study AOA in a global context.
Reflection from a free carrier front via an intraband indirect photonic transition
Authors: Gaafar Mahmoud A. , Jalas Dirk , O’Faolain Liam , Li Juntao , Krauss Thomas F. , Petrov Alexander Yu. , Eich Manfred 
Published: April 2018

AbstractThe reflection of light from moving boundaries is of interest both fundamentally and for applications in frequency conversion, but typically requires high pump power. By using a dispersion-engineered silicon photonic crystal waveguide, we are able to achieve a propagating free carrier front with only a moderate on-chip peak power of 6 W in a 6 ps-long pump pulse. We employ an intraband indirect photonic transition of a co-propagating probe, whereby the probe practically escapes from the front in the forward direction. This forward reflection has up to 35% efficiency and it is accompanied by a strong frequency upshift, which significantly exceeds that expected from the refractive index change and which is a function of group velocity, waveguide dispersion and pump power. Pump, probe and shifted probe all are around 1.5 µm wavelength which opens new possibilities for “on-chip” frequency manipulation and all-optical switching in optical telecommunications.
Two-dimensional materials in functional three-dimensional architectures with applications in photodetection and imaging
Authors: Lee Wonho , Liu Yuan , Lee Yongjun , Sharma Bhupendra K. , Shinde Sachin M. , Kim Seong Dae , Nan Kewang , Yan Zheng , Han Mengdi , Huang Yonggang , Zhang Yihui , Ahn Jong-Hyun , Rogers John A. 
Published: April 2018

AbstractEfficient and highly functional three-dimensional systems that are ubiquitous in biology suggest that similar design architectures could be useful in electronic and optoelectronic technologies, extending their levels of functionality beyond those achievable with traditional, planar two-dimensional platforms. Complex three-dimensional structures inspired by origami, kirigami have promise as routes for two-dimensional to three-dimensional transformation, but current examples lack the necessary combination of functional materials, mechanics designs, system-level architectures, and integration capabilities for practical devices with unique operational features. Here, we show that two-dimensional semiconductor/semi-metal materials can play critical roles in this context, through demonstrations of complex, mechanically assembled three-dimensional systems for light-imaging capabilities that can encompass measurements of the direction, intensity and angular divergence properties of incident light. Specifically, the mechanics of graphene and MoS2, together with strategically configured supporting polymer films, can yield arrays of photodetectors in distinct, engineered three-dimensional geometries, including octagonal prisms, octagonal prismoids, and hemispherical domes.
Westward migration of tropical cyclone rapid-intensification over the Northwestern Pacific during short duration El Niño
Authors: Guo Yi-Peng , Tan Zhe-Min 
Published: April 2018

AbstractThe El Niño-Southern Oscillation (ENSO) can significantly affect the rapid intensification of tropical cyclones over the western North Pacific (WNP). However, ENSO events have various durations, which can lead to different atmospheric and oceanic conditions. Here we show that during short duration El Niño events, the WNP tropical cyclone rapid-intensification mean occurrence position migrates westward by ~8.0° longitude, which is caused by reduced vertical wind shear, increased mid-tropospheric humidity, and enhanced tropical cyclone heat potential over the westernmost WNP. The changes in these factors are caused by westward advected upper ocean heat during the decaying phase of a short duration El Niño. As super El Niño events tend to have short durations and their frequency is projected to increase under global warming, our findings have important implications for future projections of WNP tropical cyclone activity.
A switch point in the molecular chaperone Hsp90 responding to client interaction
Authors: Rutz Daniel Andreas , Luo Qi , Freiburger Lee , Madl Tobias , Kaila Ville R. I. , Sattler Michael , Buchner Johannes 
Published: April 2018

AbstractHeat shock protein 90 (Hsp90) is a dimeric molecular chaperone that undergoes large conformational changes during its functional cycle. It has been established that conformational switch points exist in the N-terminal (Hsp90-N) and C-terminal (Hsp90-C) domains of Hsp90, however information for switch points in the large middle-domain (Hsp90-M) is scarce. Here we report on a tryptophan residue in Hsp90-M as a new type of switch point. Our study shows that this conserved tryptophan senses the interaction of Hsp90 with a stringent client protein and transfers this information via a cation–π interaction with a neighboring lysine. Mutations at this position hamper the communication between domains and the ability of a client protein to affect the Hsp90 cycle. The residue thus allows Hsp90 to transmit information on the binding of a client from Hsp90-M to Hsp90-N which is important for progression of the conformational cycle and the efficient processing of client proteins.
Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis
Authors: Silva Maria C. , Davoli-Ferreira Marcela , Medina Tiago S. , Sesti-Costa Renata , Silva Grace K. , Lopes Carla D. , Cardozo Lucas E. , Gava Fábio N. , Lyroni Konstantina , Dias Fabrício C. , Frade Amanda F. , Baron Monique , Nakaya Helder I. , Figueiredo Florêncio , Alves-Filho José C. , Cunha Fernando Q. , Tsatsanis Christos , Chevillard Christophe , Cunha-Neto Edecio , Hirsch Emilio , Silva João S. , Cunha Thiago M. 
Published: April 2018

AbstractChagas disease is caused by infection with the protozoan Trypanosoma cruzi (T. cruzi) and is an important cause of severe inflammatory heart disease. However, the mechanisms driving Chagas disease cardiomyopathy have not been completely elucidated. Here, we show that the canonical PI3Kγ pathway is upregulated in both human chagasic hearts and hearts of acutely infected mice. PI3Kγ-deficient mice and mutant mice carrying catalytically inactive PI3Kγ are more susceptible to T. cruzi infection. The canonical PI3Kγ signaling in myeloid cells is essential to restrict T. cruzi heart parasitism and ultimately to avoid myocarditis, heart damage, and death of mice. Furthermore, high PIK3CG expression correlates with low parasitism in human Chagas’ hearts. In conclusion, these results indicate an essential role of the canonical PI3Kγ signaling pathway in the control of T. cruzi infection, providing further insight into the molecular mechanisms involved in the pathophysiology of chagasic heart disease.
The use of electronic alerts in primary care computer systems to identify the excessive prescription of short-acting beta2-agonists for people with asthma: a systematic review
Authors: McKibben Shauna , De Simoni Anna , Bush Andy , Thomas Mike , Griffiths Chris 
Published: April 2018

AbstractComputers are increasingly used to improve prescribing decisions in the management of long-term conditions however the effects on asthma prescribing remain unclear. We aimed to synthesise the evidence for the use of computerised alerts that identify excessive prescribing of short-acting beta2-agonists (SABAs) to improve asthma management for people with asthma. MEDLINE, CINAHL, Embase, Cochrane and Scopus databases (1990–2016) were searched for randomised controlled trials using electronic alerts to identify excessive prescribing of SABAs for people with asthma in primary care. Inclusion eligibility, quality appraisal (Cochrane risk of bias tool) and data extraction were performed by two independent reviewers. Findings were synthesised narratively. A total of 2035 articles were screened and four trials were eligible. Three studies had low risk of bias: one reported a positive effect on our primary outcome of interest, excessive SABA prescribing; another reported positive effects on the ratio of inhaled corticosteroid (ICS)-SABA prescribing, and asthma control; a third reported no effect on outcomes of interest. One study at high risk of bias reported a reduction in exacerbations and primary care consultations. There is some evidence that electronic alerts reduce excessive prescribing of SABAs, when delivered as part of a multicomponent intervention in an integrated health care system. However due to the variation in health care systems, intervention design and outcomes measured, further research is required to establish optimal design of alerting and intervening systems.
Diffusion-Limited Growth of Microbial Colonies
Authors: Tronnolone Hayden , Tam Alexander , Szenczi Zoltán , Green J. E. F. , Balasuriya Sanjeeva , Tek Ee Lin , Gardner Jennifer M. , Sundstrom Joanna F. , Jiranek Vladimir , Oliver Stephen G. , Binder Benjamin J. 
Published: April 2018

AbstractThe emergence of diffusion-limited growth (DLG) within a microbial colony on a solid substrate is studied using a combination of mathematical modelling and experiments. Using an agent-based model of the interaction between microbial cells and a diffusing nutrient, it is shown that growth directed towards a nutrient source may be used as an indicator that DLG is influencing the colony morphology. A continuous reaction–diffusion model for microbial growth is employed to identify the parameter regime in which DLG is expected to arise. Comparisons between the model and experimental data are used to argue that the bacterium Bacillus subtilis can undergo DLG, while the yeast Saccharomyces cerevisiae cannot, and thus the non-uniform growth exhibited by this yeast must be caused by the pseudohyphal growth mode rather than limited nutrient availability. Experiments testing directly for DLG features in yeast colonies are used to confirm this hypothesis.