bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved anti-leukemia activities of adoptively transferred T cells expressing bispecific T-cell engager in mice
Authors: Liu X , Barrett D M , Jiang S , Fang C , Kalos M , Grupp S A , June C H , Zhao Y 
Published: June 2016

AbstractDespite the impressive clinical efficacy of T cells engineered to express chimeric antigen receptors (CAR-Ts), the current applications of CAR-T cell therapy are limited by major treatment-related toxicity. Thus, safer yet effective alternative approaches must be developed. In this study, we compared CD19 bispecific T-cell engager (BiTE)-transferred T cells that had been transfected by RNA electroporation with CD19 CAR RNA-transferred T cells both in vitro and in an aggressive Nalm6 leukemia mouse model. BiTEs were secreted from the transferred T cells and enabled both the transferred and bystander T cells to specifically recognize CD19+ cell lines, with increased tumor killing ability, prolonged functional persistence, increased cytokine production and potent proliferation compared with the CAR-T cells. More interestingly, in comparison with CD3/CD28 bead-stimulated T cells, T cells that were expanded by a rapid T-cell expansion protocol (REP) showed enhanced anti-tumor activities for both CAR and BiTE RNA-electroporated T cells both in vitro and in a Nalm6 mouse model (P<0.01). Furthermore, the REP T cells with BiTE RNAs showed greater efficacy in the Nalm6 leukemia model compared with REP T cells with CAR RNA (P<0.05) and resulted in complete leukemia remission.
Prophages mediate defense against phage infection through diverse mechanisms
Authors: Bondy-Denomy Joseph , Qian Jason , Westra Edze R , Buckling Angus , Guttman David S , Davidson Alan R , Maxwell Karen L 
Published: June 2016

Abstract
The activity of bacteriophages poses a major threat to bacterial survival. Upon infection, a temperate phage can either kill the host cell or be maintained as a prophage. In this state, the bacteria carrying the prophage is at risk of superinfection, where another phage injects its genetic material and competes for host cell resources. To avoid this, many phages have evolved mechanisms that alter the bacteria and make it resistant to phage superinfection. The mechanisms underlying these phentoypic conversions and the fitness consequences for the host are poorly understood, and systematic studies of superinfection exclusion mechanisms are lacking. In this study, we examined a wide range of Pseudomonas aeruginosa phages and found that they mediate superinfection exclusion through a variety of mechanisms, some of which affected the type IV pilus and O-antigen, and others that functioned inside the cell. The strongest resistance mechanism was a surface modification that we showed is cost-free for the bacterial host in a natural soil environment and in a Caenorhabditis. elegans infection model. This study represents the first systematic approach to address how a population of prophages influences phage resistance and bacterial behavior in P. aeruginosa.
Evidence for persistent and shared bacterial strains against a background of largely unique gut colonization in hospitalized premature infants
Authors: Raveh-Sadka Tali , Firek Brian , Sharon Itai , Baker Robyn , Brown Christopher T , Thomas Brian C , Morowitz Michael J , Banfield Jillian F 
Published: June 2016

Abstract
The potentially critical stage of initial gut colonization in premature infants occurs in the hospital environment, where infants are exposed to a variety of hospital-associated bacteria. Because few studies of microbial communities are strain-resolved, we know little about the extent to which specific strains persist in the hospital environment and disperse among infants. To study this, we compared 304 near-complete genomes reconstructed from fecal samples of 21 infants hospitalized in the same intensive care unit in two cohorts, over 3 years apart. The genomes represent 159 distinct bacterial strains, only 14 of which occurred in multiple infants. Enterococcus faecalis and Staphylococcus epidermidis, common infant gut colonists, exhibit diversity comparable to that of reference strains, inline with introduction of strains from infant-specific sources rather than a hospital strain pool. Unlike other infants, a pair of sibling infants shared multiple strains, even after extensive antibiotic administration, suggesting overlapping strain-sources and/or genetic selection drive microbiota similarities. Interestingly, however, five strains were detected in infants hospitalized three years apart. Three of these were also detected in multiple infants in the same year. This finding of a few widely dispersed and persistent bacterial colonizers despite overall low potential for strain dispersal among infants has implications for understanding and directing healthy colonization.
Pulse generation with ultra-superluminal pulse propagation in semiconductor heterostructures by superradiant-phase transition enhanced by transient coherent population gratings
Authors: Vasil'ev Peter P , Penty Richard V , White Ian H 
Published: June 2016

AbstractThis paper reports the observation of ultra-superluminal pulse propagation in multiple-contact semiconductor heterostructures in a superradiant emission regime, and shows definitively that it is a different class of emission from conventional spontaneous or stimulated emission. Coherent population gratings induced in the semiconductor medium under strong electrical pumping have been shown to cause a major decrease of the group refractive index, in the range of 5–40%. This decrease is much greater than that caused by conventional carrier depletion or chirp mechanisms. The decrease in refractive index in turn causes faster-than-c propagation of femtosecond pulses. The measurement also proves the existence of coherent amplification of electromagnetic pulses in semiconductors at room temperature, the coherence being strongly enhanced by interactions of the light with coherent transient gratings locked to carrier gratings. This pulse-generation technique is anticipated to have great potential in applications where highly coherent femtosecond optical pulses must be generated on demand.
Quantum mechanical effects in plasmonic structures with subnanometre gaps
Authors: Zhu Wenqi , Esteban Ruben , Borisov Andrei G. , Baumberg Jeremy J. , Nordlander Peter , Lezec Henri J. , Aizpurua Javier , Crozier Kenneth B. 
Published: June 2016

AbstractMetallic structures with nanogap features have proven highly effective as building blocks for plasmonic systems, as they can provide a wide tuning range of operating frequencies and large near-field enhancements. Recent work has shown that quantum mechanical effects such as electron tunnelling and nonlocal screening become important as the gap distances approach the subnanometre length-scale. Such quantum effects challenge the classical picture of nanogap plasmons and have stimulated a number of theoretical and experimental studies. This review outlines the findings of many groups into quantum mechanical effects in nanogap plasmons, and discusses outstanding challenges and future directions.
Synthetic mixed-signal computation in living cells
Authors: Rubens Jacob R. , Selvaggio Gianluca , Lu Timothy K. 
Published: June 2016

AbstractLiving cells implement complex computations on the continuous environmental signals that they encounter. These computations involve both analogue- and digital-like processing of signals to give rise to complex developmental programs, context-dependent behaviours and homeostatic activities. In contrast to natural biological systems, synthetic biological systems have largely focused on either digital or analogue computation separately. Here we integrate analogue and digital computation to implement complex hybrid synthetic genetic programs in living cells. We present a framework for building comparator gene circuits to digitize analogue inputs based on different thresholds. We then demonstrate that comparators can be predictably composed together to build band-pass filters, ternary logic systems and multi-level analogue-to-digital converters. In addition, we interface these analogue-to-digital circuits with other digital gene circuits to enable concentration-dependent logic. We expect that this hybrid computational paradigm will enable new industrial, diagnostic and therapeutic applications with engineered cells.
Intermolecular biparatopic trapping of ErbB2 prevents compensatory activation of PI3K/AKT via RAS–p110 crosstalk
Authors: Tamaskovic Rastislav , Schwill Martin , Nagy-Davidescu Gabriela , Jost Christian , Schaefer Dagmar C. , Verdurmen Wouter P. R. , Schaefer Jonas V. , Honegger Annemarie , Plückthun Andreas 
Published: June 2016

AbstractCompensatory mechanisms, such as relief of AKT-ErbB3-negative feedback, are known to desensitize ErbB2-dependent tumours to targeted therapy. Here we describe an adaptation mechanism leading to reactivation of the PI3K/AKT pathway during trastuzumab treatment, which occurs independently of ErbB3 re-phosphorylation. This signalling bypass of phospho-ErbB3 operates in ErbB2-overexpressing cells via RAS-PI3K crosstalk and is attributable to active ErbB2 homodimers. As demonstrated by dual blockade of ErbB2/RAS and ErbB3 by means of pharmacological inhibition, RNA interference or by specific protein binders obstructing the RAS–p110α interaction, both routes must be blocked to prevent reactivation of the PI3K/AKT pathway. Applying these general principles, we developed biparatopic designed ankyrin repeat proteins (DARPins) trapping ErbB2 in a dimerization-incompetent state, which entail pan-ErbB inhibition and a permanent OFF state in the oncogenic signalling, thereby triggering extensive apoptosis in ErbB2-addicted tumours. Thus, these novel insights into mechanisms underlying network robustness provide a guide for overcoming adaptation response to ErbB2/ErbB3-targeted therapy.
North Atlantic Deep Water Production during the Last Glacial Maximum
Authors: Howe Jacob N. W. , Piotrowski Alexander M. , Noble Taryn L. , Mulitza Stefan , Chiessi Cristiano M. , Bayon Germain 
Published: June 2016

AbstractChanges in deep ocean ventilation are commonly invoked as the primary cause of lower glacial atmospheric CO2. The water mass structure of the glacial deep Atlantic Ocean and the mechanism by which it may have sequestered carbon remain elusive. Here we present neodymium isotope measurements from cores throughout the Atlantic that reveal glacial–interglacial changes in water mass distributions. These results demonstrate the sustained production of North Atlantic Deep Water under glacial conditions, indicating that southern-sourced waters were not as spatially extensive during the Last Glacial Maximum as previously believed. We demonstrate that the depleted glacial δ13C values in the deep Atlantic Ocean cannot be explained solely by water mass source changes. A greater amount of respired carbon, therefore, must have been stored in the abyssal Atlantic during the Last Glacial Maximum. We infer that this was achieved by a sluggish deep overturning cell, comprised of well-mixed northern- and southern-sourced waters.
Engineering skyrmions in transition-metal multilayers for spintronics
Authors: Dupé B. , Bihlmayer G. , Böttcher M. , Blügel S. , Heinze S. 
Published: June 2016

AbstractMagnetic skyrmions are localized, topologically protected spin structures that have been proposed for storing or processing information due to their intriguing dynamical and transport properties. Important in terms of applications is the recent discovery of interface stabilized skyrmions as evidenced in ultra-thin transition-metal films. However, so far only skyrmions at interfaces with a single atomic layer of a magnetic material were reported, which greatly limits their potential for application in devices. Here we predict the emergence of skyrmions in [4d/Fe2/5d]n multilayers, that is, structures composed of Fe biatomic layers sandwiched between 4d and 5d transition-metal layers. In these composite structures, the exchange and the Dzyaloshinskii–Moriya interactions that control skyrmion formation can be tuned separately by the two interfaces. This allows engineering skyrmions as shown based on density functional theory and spin dynamics simulations.
A two-neuron system for adaptive goal-directed decision-making in Lymnaea
Authors: Crossley Michael , Staras Kevin , Kemenes György 
Published: June 2016

AbstractDuring goal-directed decision-making, animals must integrate information from the external environment and their internal state to maximize resource localization while minimizing energy expenditure. How this complex problem is solved by the nervous system remains poorly understood. Here, using a combined behavioural and neurophysiological approach, we demonstrate that the mollusc Lymnaea performs a sophisticated form of decision-making during food-searching behaviour, using a core system consisting of just two neuron types. The first reports the presence of food and the second encodes motivational state acting as a gain controller for adaptive behaviour in the absence of food. Using an in vitro analogue of the decision-making process, we show that the system employs an energy management strategy, switching between a low- and high-use mode depending on the outcome of the decision. Our study reveals a parsimonious mechanism that drives a complex decision-making process via regulation of levels of tonic inhibition and phasic excitation.
Interface strain in vertically stacked two-dimensional heterostructured carbon-MoS2 nanosheets controls electrochemical reactivity
Authors: Oakes Landon , Carter Rachel , Hanken Trevor , Cohn Adam P. , Share Keith , Schmidt Benjamin , Pint Cary L. 
Published: June 2016

AbstractTwo-dimensional (2D) materials offer numerous advantages for electrochemical energy storage and conversion due to fast charge transfer kinetics, highly accessible surface area, and tunable electronic and optical properties. Stacking of 2D materials generates heterogeneous interfaces that can modify native chemical and physical material properties. Here, we demonstrate that local strain at a carbon-MoS2 interface in a vertically stacked 2D material directs the pathway for chemical storage in MoS2 on lithium metal insertion. With average measured MoS2 strain of ∼0.1% due to lattice mismatch between the carbon and MoS2 layers, lithium insertion is facilitated by an energy-efficient cation-exchange transformation. This is compared with low-voltage lithium intercalation for unstrained MoS2. This observation implies that mechanical properties of interfaces in heterogeneous 2D materials can be leveraged to direct energetics of chemical processes relevant to a wide range of applications such as electrochemical energy storage and conversion, catalysis and sensing.
Resistance and Security Index of Networks: Structural Information Perspective of Network Security
Authors: Li Angsheng , Hu Qifu , Liu Jun , Pan Yicheng 
Published: June 2016

AbstractRecently, Li and Pan defined the metric of theK-dimensional structure entropy of a structured noisy datasetGto be the information that controls the formation of theK-dimensional structure "Equation missing"ofGthat is evolved by the rules, order and laws ofG, excluding the random variations that occur inG. Here, we propose the notion ofresistance of networksbased on the one- and two-dimensional structural information of graphs. Given a graphG, we define theresistance of G, written "Equation missing", as the greatest overall number of bits required to determine the code of the module that is accessible via random walks with stationary distribution inG, from which the random walks cannot escape. We show that the resistance of networks follows theresistance law of networks, that is, for a networkG, the resistance ofGis "Equation missing", where "Equation missing"and "Equation missing"are the one- and two-dimensional structure entropies ofG, respectively. Based on the resistance law, we define thesecurity index of a network Gto be the normalised resistance ofG, that is, "Equation missing". We show that the resistance and security index are both well-defined measures for the security of the networks.
Quantum Router for Single Photons Carrying Spin and Orbital Angular Momentum
Authors: Chen Yuanyuan , Jiang Dong , Xie Ling , Chen Lijun 
Published: June 2016

AbstractQuantum router is an essential element in the quantum network. Here, we present a fully quantum router based on interaction free measurement and quantum dots. The signal photonic qubit can be routed to different output ports according to one control electronic qubit. Besides, our scheme is an interferometric method capable of routing single photons carrying either spin angular momentum (SAM) or orbital angular momentum (OAM), or simultaneously carrying SAM and OAM. Then we describe a cascaded multi-level quantum router to construct a one-to-many quantum router. Subsequently we analyze the success probability by using a tunable controlled phase gate. The implementation issues are also discussed to show that this scheme is feasible.
The effector AWR5 from the plant pathogen Ralstonia solanacearum is an inhibitor of the TOR
signalling pathway
Authors: Popa Crina , Li Liang , Gil Sergio , Tatjer Laura , Hashii Keisuke , Tabuchi Mitsuaki , Coll Núria S. , Ariño Joaquín , Valls Marc 
Published: June 2016

AbstractBacterial pathogens possess complex type III effector (T3E) repertoires that are
translocated inside the host cells to cause disease. However, only a minor
proportion of these effectors have been assigned a function. Here, we show that the
T3E AWR5 from the phytopathogen Ralstonia
solanacearum is an inhibitor of TOR, a central regulator in eukaryotes
that controls the switch between cell growth and stress responses in response to
nutrient availability. Heterologous expression of AWR5 in yeast caused growth inhibition and autophagy induction coupled
to massive transcriptomic changes, unmistakably reminiscent of TOR inhibition by
rapamycin or nitrogen starvation. Detailed genetic analysis of these phenotypes in
yeast, including suppression of AWR5-induced toxicity by mutation of CDC55 and TPD3,
encoding regulatory subunits of the PP2A phosphatase, indicated that AWR5 might
exert its function by directly or indirectly inhibiting the TOR pathway upstream
PP2A. We present evidence in planta that this T3E
caused a decrease in TOR-regulated plant nitrate reductase activity and also that
normal levels of TOR and the Cdc55 homologues in plants are required for R. solanacearum virulence. Our results suggest that the
TOR pathway is a bona fide T3E target and further prove that yeast is a useful
platform for T3E function characterisation.
Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells
Authors: Fan Rong , Emery Travis , Zhang Yongguo , Xia Yuxuan , Sun Jun , Wan Jiandi 
Published: June 2016

AbstractDuring cancer metastasis, circulating tumor cells constantly experience hemodynamic shear stress in the circulation. Cellular responses to shear stress including cell viability and proliferation thus play critical roles in cancer metastasis. Here, we developed a microfluidic approach to establish a circulatory microenvironment and studied circulating human colon cancer HCT116 cells in response to a variety of magnitude of shear stress and circulating time. Our results showed that cell viability decreased with the increase of circulating time, but increased with the magnitude of wall shear stress. Proliferation of cells survived from circulation could be maintained when physiologically relevant wall shear stresses were applied. High wall shear stress (60.5 dyne/cm2), however, led to decreased cell proliferation at long circulating time (1 h). We further showed that the expression levels of β-catenin and c-myc, proliferation regulators, were significantly enhanced by increasing wall shear stress. The presented study provides a new insight to the roles of circulatory shear stress in cellular responses of circulating tumor cells in a physiologically relevant model and thus will be of interest for the study of cancer cell mechanosensing and cancer metastasis.
Risk of recurrence of retinopathy of prematurity after initial intravitreal ranibizumab therapy
Authors: Chan Joyce J. T. , Lam Carol P. S. , Kwok Madeline K. M. , Wong Raymond L. M. , Lee Gary K. Y. , Lau Winnie W. Y. , Yam Jason C. S. 
Published: June 2016

AbstractWe report our experience with the use of intravitreal ranibizumab for the treatment of retinopathy of prematurity (ROP). A retrospective review was performed on 138 consecutive infants screened at a single centre over 18 months. Intravitreal ranibizumab was offered in selected cases requiring treatment, such as aggressive posterior ROP or poor mydriasis. 2 eyes of 1 infant received intravitreal ranibizumab alone and 8 eyes of 5 infants received combined intravitreal ranibizumab and laser therapy. 3 out of 8 eyes treated initially with intravitreal ranibizumab monotherapy had persistent disease requiring laser therapy, and 3 out of 5 eyes with initial regression suffered disease recurrence at a mean of 7.6 weeks post-injection. 2 eyes treated first with laser followed by intravitreal ranibizumab had disease regression without recurrence. Our cohort demonstrate a significant rate of persistent disease and recurrence in ROP eyes treated initially with intravitreal ranibizumab monotherapy, which is greater and earlier than that reported for intravitreal bevacizumab in the BEAT-ROP study. Intravitreal ranibizumab may be useful as an initial treatment in selected cases of ROP when laser therapy as first line is suboptimal. However, close monitoring is important and adjunctive laser therapy may subsequently be needed in a majority of cases.
Direct repeat-mediated DNA deletion of the mating type MAT1-2 genes results in unidirectional mating type switching in Sclerotinia trifoliorum
Authors: Xu Liangsheng , Jardini Teresa M. , Chen Weidong 
Published: June 2016

AbstractThe necrotrophic fungal pathogen Sclerotinia trifoliorum exhibits ascospore dimorphism and unidirectional mating type switching - self-fertile strains derived from large ascospores produce both self-fertile (large-spores) and self-sterile (small-spores) offsprings in a 4:4 ratio. The present study, comparing DNA sequences at MAT locus of both self-fertile and self-sterile strains, found four mating type genes (MAT1-1-1, MAT1-1-5, MAT1-2-1 and MAT1-2-4) in the self-fertile strain. However, a 2891-bp region including the entire MAT1-2-1 and MAT1-2-4 genes had been completely deleted from the MAT locus in the self-sterile strain. Meanwhile, two copies of a 146-bp direct repeat motif flanking the deleted region were found in the self-fertile strain, but only one copy of this 146-bp motif (a part of the MAT1-1-1 gene) was present in the self-sterile strain. The two direct repeats were believed to be responsible for the deletion through homologous intra-molecular recombination in meiosis. Tetrad analyses showed that all small ascospore-derived strains lacked the missing DNA between the two direct repeats that was found in all large ascospore-derived strains. In addition, heterokaryons at the MAT locus were observed in field isolates as well as in laboratory derived isolates.