bluuebunny/crossref_metadata_2025 huggingface dataset:
Where do community-dwelling older adults with disabilities live? Distribution of disability in the United States of America by household composition and housing type
Authors: HENNING-SMITH CARRIE
Published: March 2016

There is limited research on the living arrangements of older adults with disabilities, especially research that combines household composition and housing characteristics. This paper addresses that gap with two complementary sets of logistic regression models: first, estimating the odds of disability by household composition and housing type and, second, estimating the odds of disability by living arrangement within gender and age sub-groups. Data come from the 2012 American Community Survey (N = 504,371 respondents aged 65 and older), which includes six measures of disability: cognitive, ambulatory, independent living, self-care, vision and hearing. Living alone, with children or with others was associated with higher odds of any disability, compared with living with a spouse only. Compared to those living in a single-family home, living in a mobile home or other temporary structure, or large apartment building was associated with higher odds of disability. Having a disability was associated with lower rates of living with a spouse only, alone, in a single-family home or in a small or mid-sized apartment building and higher rates of all other living arrangements. Sub-group analyses revealed differences in the relationship between living arrangements and disability by gender and age group. This information provides a baseline from which to observe trends in living arrangements and disability for older adults in the United States of America.
An incremental sampling-based approach to inspection planning: the rapidly exploring random tree of trees
Authors: Bircher Andreas , Alexis Kostas , Schwesinger Ulrich , Omari Sammy , Burri Michael , Siegwart Roland
Published: March 2016

A new algorithm, called rapidly exploring random tree of trees (RRTOT) is proposed, that aims to address the challenge of planning for autonomous structural inspection. Given a representation of a structure, a visibility model of an onboard sensor, an initial robot configuration and constraints, RRTOT computes inspection paths that provide full coverage. Sampling based techniques and a meta-tree structure consisting of multiple RRT* trees are employed to find admissible paths with decreasing cost. Using this approach, RRTOT does not suffer from the limitations of strategies that separate the inspection path planning problem into that of finding the minimum set of observation points and only afterwards compute the best possible path among them. Analysis is provided on the capability of RRTOT to find admissible solutions that, in the limit case, approach the optimal one. The algorithm is evaluated in both simulation and experimental studies. An unmanned rotorcraft equipped with a vision sensor was utilized as the experimental platform and validation of the achieved inspection properties was performed using3Dreconstruction techniques.
THE EFFECTS OF TEXTUAL ENHANCEMENT ON THE ACQUISITION OF TWO NONPARALLEL GRAMMATICAL FEATURES BY SPANISH-SPEAKING LEARNERS OF ITALIAN
Authors: Della Putta Paolo
Published: March 2016

This article investigates the learning of two syntactic structures in Italian—Pre-possessive Determiner Article (PPDA) and Differential Object Marking—that each pose specific learning difficulties for Spanish-speaking learners of Italian (SSLI), resulting from the asymmetrical relationship with corresponding structures in the learners’ L1 (Spanish). The article also examines to what extent these difficulties can be alleviated by means of a relatively implicit type of form-focused instruction (Textual Enhancement, or TE). SSLI tend to omit the article before the possessive determiner (e.g., *mia macchina) and overuse the Prepositional Accusative (PA, the Romance languages’ instance of Differential Object Marking) in canonical SVO sentences (e.g., *conoscoaMarco). Although both structures pose learning difficulties to SSLI, the learning path that leads SSLI to acquire these two features is different: SSLI have to learn to add PPDA to their interlanguage and they have to unlearn PA, a property of their L1. Sixty-eight instructed SSLI were divided in two groups. Group A read five texts where theabsenceof PA was textually enhanced; group B read the same texts where thepresenceof PPDA was enhanced. The participants took a timed grammatical judgment test before, shortly after, and two months after the instructional treatment. The results show that the effects of the TE are different for PA and PPDA, which indicates that features to be unlearned are more difficult and require more explicit instructional intervention.
An improved lower bound for arithmetic regularity
Authors: HOSSEINI KAAVE , LOVETT SHACHAR , MOSHKOVITZ GUY , SHAPIRA ASAF
Published: March 2016

The arithmetic regularity lemma due to Green [GAFA 2005] is an analogue of the famous Szemerédi regularity lemma in graph theory. It shows that for any abelian group G and any bounded function f : G → [0, 1], there exists a subgroup H ⩽ G of bounded index such that, when restricted to most cosets of H, the function f is pseudorandom in the sense that all its nontrivial Fourier coefficients are small. Quantitatively, if one wishes to obtain that for 1 − ε fraction of the cosets, the nontrivial Fourier coefficients are bounded by ε, then Green shows that |G/H| is bounded by a tower of twos of height 1/ε3. He also gives an example showing that a tower of height Ω(log 1/ε) is necessary. Here, we give an improved example, showing that a tower of height Ω(1/ε) is necessary.
Nutritional status of children <5 years of age who have a working mother: an epidemiological perspective of diarrhoeal children in urban Bangladesh
Authors: Ferdous Farzana , Das Jui , Ahmed Shahnawaz , Malek Mohammad Abdul , Das Sumon Kumar , Faruque Abu Syed Golam , Chisti Mohammod Jobayer , Ma Enbo , Wagatsuma Yukiko
Published: March 2016

Objective

The present analysis aimed to observe nutritional impacts among children <5 years of age by mother’s engagement in paid employment.

Design

Between 1996 and 2012, 21 443 children <5 years of age with diarrhoea attended the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka Hospital. They were enrolled in the hospital-based Diarrhoeal Disease Surveillance System and their relevant information was extracted from the electronic database.

Setting

The icddr,b, Bangladesh.

Subjects

The analytic sample was 19 597 children aged <5 years who had a mother aged ≤35 years with or without engagement in paid employment.

Results

Eleven per cent of the mothers (n 2051) were currently engaged in paid employment on behalf of the family. Univariate analysis showed that children with mothers engaged in paid employment had a 1·14 times higher risk of being undernourished, a 1·20 times of higher risk of being stunted, a 1·21 times higher risk of being wasted and a 1·31 times higher risk of being underweight (risk ratios) than were children with mothers not likewise engaged. Multivariate analysis showed that such associations remained significant for stunting (1·08; 95 % CI 1·00, 1·16), wasting (1·15; 95 % CI 1·06, 1·25) and underweight (1·09; 95 % CI 1·02, 1·17) after controlling for covariates.

Conclusions

Mothers’ engagement in income-generating employment was associated with undernutrition in children <5 years of age in urban Bangladesh.
A transdiagnostic cognitive behaviour therapy-based intervention in a secondary-care mental health service
Authors: Garner Emily , Gillmore Chris , Lomax Claire
Published: March 2016

Due to the growing evidence base supporting the hypothesis of common processes across different mental health problems, transdiagnostic interventions are receiving increased research attention. Transdiagnostic approaches have the potential to produce better outcomes, to reduce waiting times and to increase cost-effectiveness in stretched mental health services. Research into transdiagnostic cognitive behaviour therapy (CBT) in group format has demonstrated positive results in participants with anxiety disorders, with some studies extending the inclusion criteria to secondary and comorbid symptoms. This study evaluates a transdiagnostic CBT-based intervention, delivered by a secondary-care mental health team and includes participants with a range of diagnoses typical of this population. The real-world setting and lack of exclusion criteria based upon diagnosis provides an ecologically valid evaluation of a transdiagnostic CBT-based intervention. The results suggest that the intervention was associated with reductions in self-reported symptomatology and improvements in social functioning of individuals who attended in a secondary-care mental health service.
Occurrence and prognostic significance of cytogenetic evolution in patients with multiple myeloma
Authors: Binder M , Rajkumar S V , Ketterling R P , Dispenzieri A , Lacy M Q , Gertz M A , Buadi F K , Hayman S R , Hwa Y L , Zeldenrust S R , Lust J A , Russell S J , Leung N , Kapoor P , Go R S , Gonsalves W I , Kyle R A , Kumar S K
Published: March 2016

Cytogenetic evaluation at the time of diagnosis is essential for risk stratification in multiple myeloma, however little is known about the occurrence and prognostic significance of cytogenetic evolution during follow-up. We studied 989 patients with multiple myeloma, including 304 patients with at least two cytogenetic evaluations. Multivariable-adjusted regression models were used to assess the associations between the parameters of interest and cytogenetic evolution as well as overall survival. The prognostic significance of baseline cytogenetic abnormalities was most pronounced at the time of diagnosis and attenuated over time. In the patients with serial cytogenetic evaluations, the presence oft(11;14) at the time of diagnosis was associated with decreased odds of cytogenetic evolution during follow-up (odds ratio (OR)=0.22, 95% confidence interval (CI)=0.09–0.56,P=0.001), while the presence of at least one trisomy or tetrasomy was associated with increased odds (OR=2.96, 95% CI=1.37–6.42,P=0.006). The development of additional abnormalities during the 3 years following diagnosis was associated with increased subsequent mortality (hazard ratio=3.31, 95% CI=1.73–6.30,P<0.001). These findings emphasize the importance of the underlying clonal disease process for risk assessment and suggest that selected patients may benefit from repeated risk stratification.
Earlier infantile immune maturation is related to higher DTP vaccine responses in children
Authors: Strömbeck Anna , Lundell Anna‐Carin , Nordström Inger , Andersson Kerstin , Adlerberth Ingegerd , Wold Agnes E , Rudin Anna
Published: March 2016

There are large inter‐individual variations in vaccine‐specific antibody responses in children. We sought to investigate whether early‐life environmental factors and/or adaptive immune maturation were related to diphtheria–tetanus–pertussis (DTP) vaccine‐specific antibody levels at 18 months of age. In the prospective FARMFLORA birth‐cohort, including both farming and non‐farming families, children were immunized with DTP vaccine at 3, 5 and 12 months of age. DTP vaccine‐induced antibody levels were measured in plasma at 18 months of age. Infants’ blood samples obtained at birth, 3–5 days, 4, 18 and 36 months and at 8 years of age were analyzed for total CD4+ T‐ and B‐cell counts, proportions of naïve and memory T and B cells, and fractions of putative regulatory T cells by flow cytometry. Multivariate factor analysis was used to examine associations between immune variables and vaccine responses. The most apparent multivariate pattern was that higher anti‐DTP antibody titers at 18 months of age were associated with lower infantile total counts of T and B cells in the blood. Furthermore, lower infantile total T‐ and B‐cell blood counts were associated with higher proportions of circulating CD45RO+ memory T cells and to lower proportions of α4β7+ naïve T cells later in childhood. The multivariate findings were corroborated in univariate correlation analyses. Sex, delivery mode and dairy farm exposure were unrelated to the magnitude of DTP‐specific antibody responses. Our results thus suggest that children with a more mature/activated infantile adaptive immunity respond with higher vaccine‐induced anti‐DTP antibody levels at 18 months of age.
Engineering microbial consortia for controllable outputs
Authors: Lindemann Stephen R , Bernstein Hans C , Song Hyun-Seob , Fredrickson Jim K , Fields Matthew W , Shou Wenying , Johnson David R , Beliaev Alexander S
Published: March 2016

Much research has been invested into engineering microorganisms to perform desired biotransformations; nonetheless, these efforts frequently fall short of expected results due to the unforeseen effects of biofeedback regulation and functional incompatibility. In nature, metabolic function is compartmentalized into diverse organisms assembled into robust consortia, in which the division of labor is thought to lead to increased community efficiency and productivity. Here we consider whether and how consortia can be designed to perform bioprocesses of interest beyond the metabolic flexibility limitations of a single organism. Advances in post-genomic analysis of microbial consortia and application of high-resolution global measurements now offer the promise of systems-level understanding of how microbial consortia adapt to changes in environmental variables and inputs of carbon and energy. We argue that, when combined with appropriate modeling frameworks, systems-level knowledge can markedly improve our ability to predict the fate and functioning of consortia. Here we articulate our collective perspective on the current and future state of microbial community engineering and control while placing specific emphasis on ecological principles that promote control over community function and emergent properties.
Organic semiconductor heterojunctions: electrode-independent charge injectors for high-performance organic light-emitting diodes
Authors: Chen Yong-Hua , Ma Dong-Ge , Sun Heng-Da , Chen Jiang-Shan , Guo Qing-Xun , Wang Qiang , Zhao Yong-Biao
Published: March 2016

Organic light-emitting diodes (OLEDs) are driven by injected charges from an anode and a cathode. The low and high work function metals are necessary for the effective injection of electrons and holes, respectively. Here, we introduce a fully novel design concept using organic semiconductor heterojunctions (OSHJs) as the charge injectors for achieving highly efficient OLEDs, regardless of the work functions of the electrodes. In contrast to traditional injected charges from the electrodes, the injected charges originate from the OSHJs. The device performance was shown to be significantly improved in efficiency and stability compared to conventional OLEDs. Attractively, the OLEDs based on OSHJs as charge injectors still exhibited an impressive performance when the low work function Al was replaced by air- and chemistry-stable high work function metals, such as Au, Ag, and Cu, as the cathode contact, which has been suggested to be difficult in conventional OLEDs. This concept challenges the conventional design approach for the injection of charges and allows for the realization of practical applications of OLEDs with respect to high efficiency, selectable electrodes, and a long lifetime.
Surface Landau levels and spin states in bismuth (111) ultrathin films
Authors: Du Hongjian , Sun Xia , Liu Xiaogang , Wu Xiaojun , Wang Jufeng , Tian Mingyang , Zhao Aidi , Luo Yi , Yang Jinlong , Wang Bing , Hou J. G.
Published: March 2016

The development of next-generation electronics is much dependent on the discovery of materials with exceptional surface-state spin and valley properties. Because of that, bismuth has attracted a renewed interest in recent years. However, despite extensive studies, the intrinsic electronic transport properties of Bi surfaces are largely undetermined due to the strong interference from the bulk. Here we report the unambiguous determination of the surface-state Landau levels in Bi (111) ultrathin films using scanning tunnelling microscopy under magnetic fields perpendicular to the surface. The Landau levels of the electron-like and the hole-like carriers are accurately characterized and well described by the band structure of the Bi (111) surface from density functional theory calculations. Some specific surface spin states with a large g-factor are identified. Our findings shed light on the exploiting surface-state properties of Bi for their applications in spintronics and valleytronics.
A subunit of the oligosaccharyltransferase complex is required for interspecific gametophyte recognition in Arabidopsis
Authors: Müller Lena M. , Lindner Heike , Pires Nuno D. , Gagliardini Valeria , Grossniklaus Ueli
Published: March 2016

Species-specific gamete recognition is a key premise to ensure reproductive success and the maintenance of species boundaries. During plant pollen tube (PT) reception, gametophyte interactions likely allow the species-specific recognition of signals from the PT (male gametophyte) by the embryo sac (female gametophyte), resulting in PT rupture, sperm release, and double fertilization. This process is impaired in interspecific crosses betweenArabidopsis thalianaand related species, leading to PT overgrowth and a failure to deliver the sperm cells. Here we show thatARTUMES(ARU) specifically regulates the recognition of interspecific PTs inA. thaliana.ARU, identified in a genome-wide association study (GWAS), exclusively influences interspecific—but not intraspecific—gametophyte interactions.ARUencodes the OST3/6 subunit of the oligosaccharyltransferase complex conferring proteinN-glycosylation. Our results suggest that glycosylation patterns of cell surface proteins may represent an important mechanism of gametophyte recognition and thus speciation.
Structural basis for selective recognition of acyl chains by the membrane-associated acyltransferase PatA
Authors: Albesa-Jové David , Svetlíková Zuzana , Tersa Montse , Sancho-Vaello Enea , Carreras-González Ana , Bonnet Pascal , Arrasate Pedro , Eguskiza Ander , Angala Shiva K. , Cifuente Javier O. , Korduláková Jana , Jackson Mary , Mikušová Katarína , Guerin Marcelo E.
Published: March 2016

The biosynthesis of phospholipids and glycolipids are critical pathways for virtually all cell membranes. PatA is an essential membrane associated acyltransferase involved in the biosynthesis of mycobacterial phosphatidyl-myo-inositol mannosides (PIMs). The enzyme transfers a palmitoyl moiety from palmitoyl–CoA to the 6-position of the mannose ring linked to 2-position of inositol in PIM1/PIM2. We report here the crystal structures of PatA from Mycobacterium smegmatis in the presence of its naturally occurring acyl donor palmitate and a nonhydrolyzable palmitoyl–CoA analog. The structures reveal an α/β architecture, with the acyl chain deeply buried into a hydrophobic pocket that runs perpendicular to a long groove where the active site is located. Enzyme catalysis is mediated by an unprecedented charge relay system, which markedly diverges from the canonical HX4D motif. Our studies establish the mechanistic basis of substrate/membrane recognition and catalysis for an important family of acyltransferases, providing exciting possibilities for inhibitor design.
αv Integrins combine with LC3 and atg5 to regulate Toll-like receptor signalling in B cells
Authors: Acharya Mridu , Sokolovska Anna , Tam Jenny M. , Conway Kara L. , Stefani Caroline , Raso Fiona , Mukhopadhyay Subhankar , Feliu Marianela , Paul Elahna , Savill John , Hynes Richard O. , Xavier Ramnik J. , Vyas Jatin M. , Stuart Lynda M. , Lacy-Hulbert Adam
Published: March 2016

Integrin signalling triggers cytoskeletal rearrangements, including endocytosis and exocytosis of integrins and other membrane proteins. In addition to recycling integrins, this trafficking can also regulate intracellular signalling pathways. Here we describe a role for αv integrins in regulating Toll-like receptor (TLR) signalling by modulating intracellular trafficking. We show that deletion of αv or β3 causes increased B-cell responses to TLR stimulation in vitro, and αv-conditional knockout mice have elevated antibody responses to TLR-ligand-associated antigens. αv regulates TLR signalling by promoting recruitment of the autophagy component LC3 (microtubule-associated proteins 1 light chain 3) to TLR-containing endosomes, which is essential for progression from NF-κB to IRF signalling, and ultimately for traffic to lysosomes where signalling is terminated. Disruption of LC3 recruitment leads to prolonged NF-κB signalling and increased B-cell proliferation and antibody production. This work identifies a previously unrecognized role for αv and the autophagy components LC3 and atg5 in regulating TLR signalling and B-cell immunity.
IL-17-producing γδ T cells enhance bone regeneration
Authors: Ono Takehito , Okamoto Kazuo , Nakashima Tomoki , Nitta Takeshi , Hori Shohei , Iwakura Yoichiro , Takayanagi Hiroshi
Published: March 2016

Immune responses are crucial not only for host defence against pathogens but also for tissue maintenance and repair after injury. Lymphocytes are involved in the healing process after tissue injury, including bone fracture and muscle damage. However, the specific immune cell subsets and mediators of healing are not entirely clear. Here we show that γδ T cells produce IL-17A, which promotes bone formation and facilitates bone fracture healing. Repair is impaired in IL-17A-deficient mice due to a defect in osteoblastic bone formation. IL-17A accelerates bone formation by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells. This study identifies a novel role for IL-17-producing γδ T cells in skeletal tissue regeneration.
A three-dimensional actuated origami-inspired transformable metamaterial with multiple degrees of freedom
Authors: Overvelde Johannes T.B. , de Jong Twan A. , Shevchenko Yanina , Becerra Sergio A. , Whitesides George M. , Weaver James C. , Hoberman Chuck , Bertoldi Katia
Published: March 2016

Reconfigurable devices, whose shape can be drastically altered, are central to expandable shelters, deployable space structures, reversible encapsulation systems and medical tools and robots. All these applications require structures whose shape can be actively controlled, both for deployment and to conform to the surrounding environment. While most current reconfigurable designs are application specific, here we present a mechanical metamaterial with tunable shape, volume and stiffness. Our approach exploits a simple modular origami-like design consisting of rigid faces and hinges, which are connected to form a periodic structure consisting of extruded cubes. We show both analytically and experimentally that the transformable metamaterial has three degrees of freedom, which can be actively deformed into numerous specific shapes through embedded actuation. The proposed metamaterial can be used to realize transformable structures with arbitrary architectures, highlighting a robust strategy for the design of reconfigurable devices over a wide range of length scales.
Hexose enhances oligonucleotide delivery and exon skipping in dystrophin-deficient mdx mice
Authors: Han Gang , Gu Ben , Cao Limin , Gao Xianjun , Wang Qingsong , Seow Yiqi , Zhang Ning , Wood Matthew J. A. , Yin HaiFang
Published: March 2016

Carbohydrate-based infusion solutions are widely used in the clinic. Here we show that co-administration of phosphorodiamidate morpholino oligomers (PMOs) with glucose enhances exon-skipping activity in Duchenne muscular dystrophy (DMD)mdxmice. We identify a glucose–fructose (GF) formulation that potentiates PMO activity, completely corrects aberrantDmdtranscripts, restores dystrophin levels in skeletal muscles and achieves functional rescue without detectable toxicity. This activity is attributed to enhancement of GF-mediated PMO uptake in the muscle. We demonstrate that PMO cellular uptake is energy dependent, and that ATP from GF metabolism contributes to enhanced cellular uptake of PMO in the muscle. Collectively, we show that GF potentiates PMO activity by replenishing cellular energy stores under energy-deficient conditions inmdxmice. Our findings provide mechanistic insight into hexose-mediated oligonucleotide delivery and have important implications for the development of DMD exon-skipping therapy.
Thermal selectivity of intermolecular versus intramolecular reactions on surfaces
Authors: Cirera Borja , Giménez-Agulló Nelson , Björk Jonas , Martínez-Peña Francisco , Martin-Jimenez Alberto , Rodriguez-Fernandez Jonathan , Pizarro Ana M. , Otero Roberto , Gallego José M. , Ballester Pablo , Galan-Mascaros José R. , Ecija David
Published: March 2016

On-surface synthesis is a promising strategy for engineering heteroatomic covalent nanoarchitectures with prospects in electronics, optoelectronics and photovoltaics. Here we report the thermal tunability of reaction pathways of a molecular precursor in order to select intramolecular versus intermolecular reactions, yielding monomeric or polymeric phthalocyanine derivatives, respectively. Deposition of tetra-aza-porphyrin species bearing ethyl termini on Au(111) held at room temperature results in a close-packed assembly. Upon annealing from room temperature to 275 °C, the molecular precursors undergo a series of covalent reactions via their ethyl termini, giving rise to phthalocyanine tapes. However, deposition of the tetra-aza-porphyrin derivatives on Au(111) held at 300 °C results in the formation and self-assembly of monomeric phthalocyanines. A systematic scanning tunnelling microscopy study of reaction intermediates, combined with density functional calculations, suggests a [2+2] cycloaddition as responsible for the initial linkage between molecular precursors, whereas the monomeric reaction is rationalized as an electrocyclic ring closure.
Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report
Authors: Zhang Wen-ying , Wang Yao , Guo Ye-lei , Dai Han-ren , Yang Qing-ming , Zhang Ya-jing , Zhang Yan , Chen Mei-xia , Wang Chun-meng , Feng Kai-chao , Li Su-xia , Liu Yang , Shi Feng-xia , Luo Can , Han Wei-dong
Published: March 2016

Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis. Chimeric Antigen Receptor (CAR)-modified T cells (CART cells) that targeted CD20 were effective in a phase I clinical trial for patients with advanced B-cell lymphomas. We performed a phase IIa trial to further assess the safety and efficacy of administering autologous anti-CD20 CART (CART-20) cells to patients with refractory or relapsed CD20+ B-cell lymphoma. Eleven patients were enrolled, and seven patients underwent cytoreductive chemotherapy to debulk the tumors and deplete the lymphocytes before receiving T-cell infusions. The overall objective response rate was 9 of 11 (81.8%), with 6 complete remissions (CRs) and 3 partial remissions; no severe toxicity was observed. The median progression-free survival lasted for >6 months, and 1 patient had a 27-month continuous CR. A significant inverse correlation between the levels of the CAR gene and disease recurrence or progression was observed. Clinically, the lesions in special sites, specifically the spleen and testicle, were refractory to CART-20 treatment. Collectively, these results together with our data from phase I strongly demonstrated the feasibility and efficacy of CART-20 treatment in lymphomas and suggest large-scale patient recruitment in a future study. This study was registered at www.clinicaltrials.org as NCT01735604.
Precession and nutation dynamics of nonlinearly coupled non-coaxial three-dimensional matter wave vortices
Authors: Driben R. , Konotop V. V. , Meier T.
Published: March 2016

Nonlinearity is the driving force for numerous important effects in nature typically showing transitions between different regimes, regular, chaotic or catastrophic behavior. Localized nonlinear modes have been the focus of intense research in areas such as fluid and gas dynamics, photonics, atomic and solid state physics etc. Due to the richness of the behavior of nonlinear systems and due to the severe numerical demands of accurate three-dimensional (3D) numerical simulations presently only little knowledge is available on the dynamics of complex nonlinear modes in 3D. Here, we investigate the dynamics of 3D non-coaxial matter wave vortices that are trapped in a parabolic potential and interact via a repulsive nonlinearity. Our numerical simulations demonstrate the existence of an unexpected and fascinating nonlinear regime that starts immediately when the nonlinearity is switched-on and is characterized by a smooth dynamics representing torque-free precession with nutations. The reported motion is proven to be robust regarding various effects such as the number of particles, dissipation and trap deformations and thus should be observable in suitably designed experiments. Since our theoretical approach, i.e., coupled nonlinear Schrödinger equations, is quite generic, we expect that the obtained novel dynamical behavior should also exist in other nonlinear systems.
An implantable compound-releasing capsule triggered on demand by ultrasound
Authors: Ordeig Olga , Chin Sau Yin , Kim Sohyun , Chitnis Parag V. , Sia Samuel K.
Published: March 2016

Implantable devices have a large potential to improve human health, but they are often made of biofouling materials that necessitate special coatings, rely on electrical connections for external communication, and require a continuous power source. This paper demonstrates an alternative platform, which we call iTAG (implantable thermally actuated gel), where an implanted capsule can be wirelessly controlled by ultrasound to trigger the release of compounds. We constructed a millimeter-sized capsule containing a co-polymer gel (NiPAAm-co-AAm) that contracts above body temperature (i.e. at 45 °C) to release compounds through an opening. This gel-containing capsule is biocompatible and free of toxic electronic or battery components. An ultrasound hardware, with a focused ultrasound (FUS) transducer and a co-axial A-mode imaging transducer, was used to image the capsule (to monitor in real time its position, temperature, and effectiveness of dose delivery), as well as to trigger a rapid local rise in temperature, contraction of gel, and release of compounds in vitro and in vivo. The combination of this gel-based capsule and compact ultrasound hardware can serve as a platform for triggering local release of compounds, including potentially in deep tissue, to achieve tailored personalized therapy.
Determination of cyanidin 3-glucoside in rat brain, liver and kidneys by UPLC/MS-MS and its application to a short-term pharmacokinetic study
Authors: Fornasaro Stefano , Ziberna Lovro , Gasperotti Mattia , Tramer Federica , Vrhovšek Urška , Mattivi Fulvio , Passamonti Sabina
Published: March 2016

Anthocyanins exert neuroprotection in various in vitro and in vivo experimental models. However, no details regarding their brain-related pharmacokinetics are so far available to support claims about their direct neuronal bioactivity as well as to design proper formulations of anthocyanin-based products. To gather this missing piece of knowledge, we intravenously administered a bolus of 668 nmol cyanidin 3-glucoside (C3G) in anaesthetized Wistar rats and shortly after (15 s to 20 min) we collected blood, brain, liver, kidneys and urine samples. Extracts thereof were analysed for C3G and its expected metabolites using UPLC/MS-MS. The data enabled to calculate a set of pharmacokinetics parameters. The main finding was the distinctive, rapid distribution of C3G in the brain, with an apparently constant plasma/brain ratio in the physiologically relevant plasma concentration range (19–355 nM). This is the first report that accurately determines the distribution pattern of C3G in the brain, paving the way to the rational design of future tests of neuroprotection by C3G in animal models and humans.
Reusable nanosilver-coated magnetic particles for ultrasensitive SERS-based detection of malachite green in water samples
Authors: Song Dan , Yang Rong , Wang Chongwen , Xiao Rui , Long Feng
Published: March 2016

A novel nanosilver-deposited silica-coated Fe3O4 magnetic particle (Fe3O4@SiO2@Ag) with uniform size, good SERS activity and magnetic responsiveness was synthesized using amination polymer. The Fe3O4@SiO2@Ag magnetic particles have been successfully applied for ultrasensitive SERS detection of malachite green (MG) in water samples. The mechanism is that MG can be adsorbed on the silver surface of nanosilver-coated magnetic particles via one nitrogen atom and the Raman signal intensity of MG is significantly enhanced by the nanosilver layer formed on the magnetic particles. The developed sensing system exhibited a sensitive response to MG in the range of 10 fM to 100 μM with a low limit of detection (LOD) 2 fM under optimal conditions. The LOD was several orders of magnitude lower than those of other methods. This SERS-based sensor showed good reproducibility and stability for MG detection. The silver-coated magnetic particles could easily be regenerated as SERS substrates only using low pH solution for multiple sensing events. The recovery of MG added to several water samples at different concentrations ranged from 90% to 110%. The proposed method facilitates the ultrasensitive analysis of dyes to satisfy the high demand for ensuring the safety of water sources.
Superconductivity of novel tin hydrides (SnnHm) under pressure
Authors: Mahdi Davari Esfahani M. , Wang Zhenhai , Oganov Artem R. , Dong Huafeng , Zhu Qiang , Wang Shengnan , Rakitin Maksim S. , Zhou Xiang-Feng
Published: March 2016

With the motivation of discovering high-temperature superconductors, evolutionary algorithm USPEX is employed to search for all stable compounds in the Sn-H system. In addition to the traditional SnH4, new hydrides SnH8, SnH12and SnH14are found to be thermodynamically stable at high pressure. Dynamical stability and superconductivity of tin hydrides are systematically investigated. I"Equation missing"m2-SnH8, C2/m-SnH12and C2/m-SnH14exhibit higher superconducting transition temperatures of 81, 93 and 97 K compared to the traditional compound SnH4 with Tcof 52 K at 200 GPa. An interesting bent H3–group in I"Equation missing"m2-SnH8and novel linear H"Equation missing"in C2/m-SnH12are observed. All the new tin hydrides remain metallic over their predicted range of stability. The intermediate-frequency wagging and bending vibrations have more contribution to electron-phonon coupling parameter than high-frequency stretching vibrations of H2 and H3.
In silico assessment of primers for eDNA studies using PrimerTree and application to characterize the biodiversity surrounding the Cuyahoga River
Authors: Cannon M. V. , Hester J. , Shalkhauser A. , Chan E. R. , Logue K. , Small S. T. , Serre D.
Published: March 2016

Analysis of environmental DNA (eDNA) enables the detection of species of interest from water and soil samples, typically using species-specific PCR. Here, we describe a method to characterize the biodiversity of a given environment by amplifying eDNA using primer pairs targeting a wide range of taxa and high-throughput sequencing for species identification. We tested this approach on 91 water samples of 40 mL collected along the Cuyahoga River (Ohio, USA). We amplified eDNA using 12 primer pairs targeting mammals, fish, amphibians, birds, bryophytes, arthropods, copepods, plants and several microorganism taxa and sequenced all PCR products simultaneously by high-throughput sequencing. Overall, we identified DNA sequences from 15 species of fish, 17 species of mammals, 8 species of birds, 15 species of arthropods, one turtle and one salamander. Interestingly, in addition to aquatic and semi-aquatic animals, we identified DNA from terrestrial species that live near the Cuyahoga River. We also identified DNA from one Asian carp species invasive to the Great Lakes but that had not been previously reported in the Cuyahoga River. Our study shows that analysis of eDNA extracted from small water samples using wide-range PCR amplification combined with high-throughput sequencing can provide a broad perspective on biological diversity.
Pathways for Modulating Exosome Lipids Identified By High-Density Lipoprotein-Like Nanoparticle Binding to Scavenger Receptor Type B-1
Authors: Angeloni Nicholas L. , McMahon Kaylin M. , Swaminathan Suchitra , Plebanek Michael P. , Osman Iman , Volpert Olga V. , Thaxton C. Shad
Published: March 2016

Exosomes are produced by cells to mediate intercellular communication and have been shown to perpetuate diseases, including cancer. New tools are needed to understand exosome biology, detect exosomes from specific cell types in complex biological media and to modify exosomes. Our data demonstrate a cellular pathway whereby membrane-bound scavenger receptor type B-1 (SR-B1) in parent cells becomes incorporated into exosomes. We tailored synthetic HDL-like nanoparticles (HDL NP), high-affinity ligands for SR-B1, to carry a fluorescently labeled phospholipid. Data show SR-B1-dependent transfer of the fluorescent phospholipid from HDL NPs to exosomes. Modified exosomes are stable in serum and can be directly detected using flow cytometry. As proof-of-concept, human serum exosomes were found to express SR-B1 and HDL NPs can be used to label and isolate them. Ultimately, we discovered a natural cellular pathway and nanoparticle-receptor pair that enables exosome modulation, detection and isolation.
Chloroquine enhances TRAIL-mediated apoptosis through up-regulation of DR5 by stabilization of mRNA and protein in cancer cells
Authors: Park Eun Jung , Min Kyoung-jin , Choi Kyeong Sook , Kubatka Peter , Kruzliak Peter , Kim Dong Eun , Kwon Taeg Kyu
Published: March 2016

Chloroquine (CQ), an anti-malarial drug, has immune-modulating activity and lysosomotropic activity. In this study, we investigated CQ sensitizes TRAIL-mediated apoptosis in human renal cancer Caki cells. Combination of CQ and TRAIL significantly induces apoptosis in human renal cancer Caki cells and various human cancer cells, but not in normal mouse kidney cells (TMCK-1) and human mesangial cells (MC). CQ up-regulates DR5 mRNA and protein expression in a dose- and time- dependent manner. Interestingly, CQ regulates DR5 expression through the increased stability in the mRNA and protein of DR5, rather than through the increased transcriptional activity of DR5. Moreover, we found that CQ decreased the expression of Cbl, an E3 ligase of DR5, and knock-down of Cbl markedly enhanced DR5 up-regulation. Other lysosomal inhibitors, including monensin and nigericin, also up-regulated DR5 and sensitized TRAIL-mediated apoptosis. Therefore, this study demonstrates that lysosomal inhibition by CQ may sensitize TRAIL-mediated apoptosis in human renal cancer Caki cells via DR5 up-regulation.
Study of individual erythrocyte deformability susceptibility to INFeD and ethanol using a microfluidic chip
Authors: Liu Lihong , Huang Sha , Xu Xiaoying , Han Jongyoon
Published: March 2016

Human red blood cells (RBCs) deformability in vitro was assessed during iron dextran (INFeD) loading and/or ethanol co-administration using microfluidic deformability screening. The results showed donor-specific variations in dose dependent deformability shift were revealed below 500 μg/mL iron dextran. Two out of nine blood samples exhibited significant cell stiffening at 500 μg/mL iron dextran loading concentration (p < 0.05, Tukey test). More interestingly, co-administration of moderate amount of ethanol was identified to have significant protective effects on RBC deformability. We also noted that ethanol can reverse the deformability of impaired RBCs. Meanwhile obvious donor dependent response to ethanol administration on RBC deformability was noted using our biomimetic microfluidic chip.
Association between secondary thrombocytosis and viral respiratory tract infections in children
Authors: Zheng Shou-Yan , Xiao Qiu-Yan , Xie Xiao-Hong , Deng Yu , Ren Luo , Tian Dai-Yin , Luo Zheng-Xiu , Luo Jian , Fu Zhou , Huang Ai-Long , Liu En-Mei
Published: March 2016

Secondary thrombocytosis (ST) is frequently observed in children with a variety of clinical conditions. The leading cause of ST is respiratory tract infection (RTI) in children. Nasopharyngeal aspirate samples were collected and assessed for common respiratory viruses. The relationships between virus infections and secondary thrombocytosis were analyzed retrospectively. The blood platelet count and the presence of respiratory viruses were determined for 3156 RTI patients and 817 (25.9%) cases with platelet ≥500 × 109/L were considered as the thrombocytosis group. Compared with the normal group, the detection rates of respiratory syncytial virus (RSV) and human rhinovirus (HRV) were significantly higher in the thrombocytosis group (P = 0.017 and 0.042, respectively). HRV single infection was a risk factor associated with thrombocytosis [odds ratio (OR) = 1.560, 95% confidence interval (CI) = 1.108–2.197]. Furthermore, ST was more likely to occur in younger patients who had clinical manifestations of wheezing and dyspnea and who had been diagnosed with bronchiolitis. Furthermore, the course of disease lasted longer in these patients. ST is associated with viral respiratory tract infections, especially RSV and HRV infections. HRV single infection is a risk factor associated with thrombocytosis.
The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells
Authors: Dong Hye-Jin , Jang Gyu-Beom , Lee Hwa-Yong , Park Se-Ra , Kim Ji-Young , Nam Jeong-Seok , Hong In-Sun
Published: March 2016

Hypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. However, candidate hypoxia-regulated mediators specifically relevant to the stemness-related functions of colorectal CSCs have not been examined in detail. In the present study, we showed that hypoxia specifically promoted the self-renewal potential of CSCs. Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like phenotypes and the level of Id2 expression in colorectal-cancer cells. Importantly, the levels of hypoxia-induced CSC-sphere formation and Id2 expression were successfully attenuated by treatment with a Wnt/β-catenin-signaling inhibitor. We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44+ subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression. Taken together, these data suggested that Wnt/β-catenin signaling mediated the hypoxia-induced self-renewal potential of colorectal-cancer CSCs through reactivating Id2 expression.
Vaginal Fibroblastic Cells from Women with Pelvic Organ Prolapse Produce Matrices with Increased Stiffness and Collagen Content
Authors: Ruiz-Zapata Alejandra M. , Kerkhof Manon H. , Ghazanfari Samaneh , Zandieh-Doulabi Behrouz , Stoop Reinout , Smit Theo H. , Helder Marco N.
Published: March 2016

Pelvic organ prolapse (POP) is characterised by the weakening of the pelvic floor support tissues, and often by subsequent prolapse of the bladder outside the body, i.e. cystocele. The bladder is kept in place by the anterior vaginal wall which consists of a dense extracellular matrix rich in collagen content that is maintained and remodelled by fibroblastic cells, i.e. fibroblasts and myofibroblasts. Since altered matrix production influences tissue quality, and myofibroblasts are involved in normal and pathological soft tissue repair processes, we evaluated matrix production of cells derived from pre- and post-menopausal POP and non-POP control anterior vaginal wall tissues. Results showed that cells from postmenopausal POP women deposited matrices with high percentage of collagen fibres with less anisotropic orientation and increased stiffness than those produced by controls. There was a transient increase in myofibroblastic phenotype that was lost after the peak of tissue remodelling. In conclusion, affected fibroblasts from postmenopausal prolapsed tissues produced altered matrices in vitro compared to controls. Such aberrant altered matrix production does not appear to be a consequence of abnormal phenotypical changes towards the myofibroblastic lineage.
Extensible Multiplex Real-time PCR of MicroRNA Using Microparticles
Authors: Jung Seungwon , Kim Junsun , Lee Dong Jin , Oh Eun Hae , Lim Hwasup , Kim Kwang Pyo , Choi Nakwon , Kim Tae Song , Kim Sang Kyung
Published: March 2016

Multiplex quantitative real-time PCR (qPCR), which measures multiple DNAs in a given sample, has received significant attention as a mean of verifying the rapidly increasing genetic targets of interest in single phenotype. Here we suggest a readily extensible qPCR for the expression analysis of multiple microRNA (miRNA) targets using microparticles of primer-immobilized networks as discrete reactors. Individual particles, 200~500 μm in diameter, are identified by two-dimensional codes engraved into the particles and the non-fluorescent encoding allows high-fidelity acquisition of signal in real-time PCR. During the course of PCR, the amplicons accumulate in the volume of the particles with high reliability and amplification efficiency over 95%. In a quick assay comprising of tens of particles holding different primers, each particle brings the independent real-time amplification curve representing the quantitative information of each target. Limited amount of sample was analyzed simultaneously in single chamber through this highly multiplexed qPCR; 10 kinds of miRNAs from purified extracellular vesicles (EVs).
Activation of c-Jun predicts a poor response to sorafenib in hepatocellular carcinoma: Preliminary Clinical Evidence
Authors: Chen Wei , Xiao Weikai , Zhang Kunsong , Yin Xiaoyu , Lai Jiaming , Liang Lijian , Chen Dong
Published: March 2016

We determined the mitogen-activated protein kinase (MAPK) gene expression profile of acquired resistance in sorafenib-sensitive hepatocellular carcinoma (HCC) cells and aimed to identify c-Jun as an important molecule mediating the efficacy of sorafenib. Differences in gene expression of the MAPK signaling between untreated and sorafenib-treated HCC cell lines were investigated using real-time polymerase chain reaction array. Western blot and real-time PCR further evaluated the expression of c-Jun. Pathological specimens from 50 patients with advanced HCC were collected to measure p-c-Jun expression. Sorafenib-resistant HCC cells demonstrated greater levels of basal c-Jun mRNA and protein compared with sorafenib-sensitive HCC cells. Sorafenib activated p-c-Jun in a dose- and time-dependent manner in PLC/PRF/5 and MHCC97H cell lines. Decreased expression levels of 6 genes after sorafenib treatment suggested a robust inhibitory impact of sorafenib on MAPK signaling in HCC cells. c-Jun and p-c-Jun expression levels were inversely correlated with the efficacy of sorafenib; a high expression level of p-c-Jun was associated with resistance to sorafenib and poor overall survival in patients with clinical HCC. p-c-Jun may act as a biomarker for predicting responses of sorafenib treatment, thus advocating targeting of JNK/c-Jun signaling as an optimal therapeutic strategy in a subset of HCC.