bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strength and ductility with {10͞11} — {10͞12} double twinning in a magnesium alloy
Authors: Lentz M. , Risse M. , Schaefer N. , Reimers W. , Beyerlein I. J. 
Published: April 2016

AbstractBased on their high specific strength and stiffness, magnesium alloys are attractive for lightweight applications in aerospace and transportation, where weight saving is crucial for the reduction of carbon dioxide emissions. Unfortunately, the ductility of magnesium alloys is usually limited. It is thought that one reason for the lack of ductility is that the development of "Equation missing"—"Equation missing" double twins (DTW) cause premature failure of magnesium alloys. Here we show with a magnesium alloy containing 4 wt% lithium, that the same impressively large compression failure strains can be achieved with DTWs as without. The DTWs form stably across the microstructure and continuously throughout straining, forming three-dimensional intra-granular networks, a potential strengthening mechanism. We rationalize that relatively easier <c+a> slip characteristic of this alloy plastically relaxed the localized stress concentrations that DTWs can generate. This result may provide key insight and an alternative perspective towards designing formable and strong magnesium alloys.
mTORC1 and CK2 coordinate ternary and eIF4F complex assembly
Authors: Gandin Valentina , Masvidal Laia , Cargnello Marie , Gyenis Laszlo , McLaughlan Shannon , Cai Yutian , Tenkerian Clara , Morita Masahiro , Balanathan Preetika , Jean-Jean Olivier , Stambolic Vuk , Trost Matthias , Furic Luc , Larose Louise , Koromilas Antonis E. , Asano Katsura , Litchfield David , Larsson Ola , Topisirovic Ivan 
Published: April 2016

AbstractTernary complex (TC) and eIF4F complex assembly are the two major rate-limiting steps in translation initiation regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway, respectively. How TC and eIF4F assembly are coordinated, however, remains largely unknown. We show that mTOR suppresses translation of mRNAs activated under short-term stress wherein TC recycling is attenuated by eIF2α phosphorylation. During acute nutrient or growth factor stimulation, mTORC1 induces eIF2β phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2α phosphorylation and bolsters TC recycling. Accordingly, eIF2β mediates the effect of mTORC1 on protein synthesis and proliferation. In addition, we demonstrate a formerly undocumented role for CK2 in regulation of translation initiation, whereby CK2 stimulates phosphorylation of eIF2β and simultaneously bolsters eIF4F complex assembly via the mTORC1/4E-BP pathway. These findings imply a previously unrecognized mode of translation regulation, whereby mTORC1 and CK2 coordinate TC and eIF4F complex assembly to stimulate cell proliferation.
Quantized conductance coincides with state instability and excess noise in tantalum oxide memristors
Authors: Yi Wei , Savel'ev Sergey E. , Medeiros-Ribeiro Gilberto , Miao Feng , Zhang M.-X. , Yang J. Joshua , Bratkovsky Alexander M. , Williams R. Stanley 
Published: April 2016

AbstractTantalum oxide memristors can switch continuously from a low-conductance semiconducting to a high-conductance metallic state. At the boundary between these two regimes are quantized conductance states, which indicate the formation of a point contact within the oxide characterized by multistable conductance fluctuations and enlarged electronic noise. Here, we observe diverse conductance-dependent noise spectra, including a transition from 1/f2 (activated transport) to 1/f (flicker noise) as a function of the frequency f, and a large peak in the noise amplitude at the conductance quantum GQ=2e2/h, in contrast to suppressed noise at the conductance quantum observed in other systems. We model the stochastic behaviour near the point contact regime using Molecular Dynamics–Langevin simulations and understand the observed frequency-dependent noise behaviour in terms of thermally activated atomic-scale fluctuations that make and break a quantum conductance channel. These results provide insights into switching mechanisms and guidance to device operating ranges for different applications.
Repression of GSK3 restores NK cell cytotoxicity in AML patients
Authors: Parameswaran Reshmi , Ramakrishnan Parameswaran , Moreton Stephen A. , Xia Zhiqiang , Hou Yongchun , Lee Dean A. , Gupta Kalpana , deLima Marcos , Beck Rose C. , Wald David N. 
Published: April 2016

AbstractNatural killer cells from acute myeloid leukaemia patients (AML-NK) show a dramatic impairment in cytotoxic activity. The exact reasons for this dysfunction are not fully understood. Here we show that the glycogen synthase kinase beta (GSK3β) expression is elevated in AML-NK cells. Interestingly, GSK3 overexpression in normal NK cells impairs their ability to kill AML cells, while genetic or pharmacological GSK3 inactivation enhances their cytotoxic activity. Mechanistic studies reveal that the increased cytotoxic activity correlates with an increase in AML-NK cell conjugates. GSK3 inhibition promotes the conjugate formation by upregulating LFA expression on NK cells and by inducing ICAM-1 expression on AML cells. The latter is mediated by increased NF-κB activation in response to TNF-α production by NK cells. Finally, GSK3-inhibited NK cells show significant efficacy in human AML mouse models. Overall, our work provides mechanistic insights into the AML-NK dysfunction and a potential NK cell therapy strategy.
Fabrication of slender elastic shells by the coating of curved surfaces
Authors: Lee A. , Brun P. -T. , Marthelot J. , Balestra G. , Gallaire F. , Reis P. M. 
Published: April 2016

AbstractVarious manufacturing techniques exist to produce double-curvature shells, including injection, rotational and blow molding, as well as dip coating. However, these industrial processes are typically geared for mass production and are not directly applicable to laboratory research settings, where adaptable, inexpensive and predictable prototyping tools are desirable. Here, we study the rapid fabrication of hemispherical elastic shells by coating a curved surface with a polymer solution that yields a nearly uniform shell, upon polymerization of the resulting thin film. We experimentally characterize how the curing of the polymer affects its drainage dynamics and eventually selects the shell thickness. The coating process is then rationalized through a theoretical analysis that predicts the final thickness, in quantitative agreement with experiments and numerical simulations of the lubrication flow field. This robust fabrication framework should be invaluable for future studies on the mechanics of thin elastic shells and their intrinsic geometric nonlinearities.
Multi-terminal Josephson junctions as topological matter
Authors: Riwar Roman-Pascal , Houzet Manuel , Meyer Julia S. , Nazarov Yuli V. 
Published: April 2016

AbstractTopological materials and their unusual transport properties are now at the focus of modern experimental and theoretical research. Their topological properties arise from the bandstructure determined by the atomic composition of a material and as such are difficult to tune and naturally restricted to ≤3 dimensions. Here we demonstrate that n-terminal Josephson junctions with conventional superconductors may provide novel realizations of topology in n−1 dimensions, which have similarities, but also marked differences with existing 2D or 3D topological materials. For n≥4, the Andreev subgap spectrum of the junction can accommodate Weyl singularities in the space of the n−1 independent superconducting phases, which play the role of bandstructure quasimomenta. The presence of these Weyl singularities enables topological transitions that are manifested experimentally as changes of the quantized transconductance between two voltage-biased leads, the quantization unit being 4e2/h, where e is the electric charge and h is the Planck constant.
A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer
Authors: Wu Sherry Y. , Rupaimoole Rajesha , Shen Fangrong , Pradeep Sunila , Pecot Chad V. , Ivan Cristina , Nagaraja Archana S. , Gharpure Kshipra M. , Pham Elizabeth , Hatakeyama Hiroto , McGuire Michael H. , Haemmerle Monika , Vidal-Anaya Viviana , Olsen Courtney , Rodriguez-Aguayo Cristian , Filant Justyna , Ehsanipour Ehsan A. , Herbrich Shelley M. , Maiti Sourindra N. , Huang Li , Kim Ji Hoon , Zhang Xinna , Han Hee-Dong , Armaiz-Pena Guillermo N. , Seviour Elena G. , Tucker Sue , Zhang Min , Yang Da , Cooper Laurence J. N. , Ali-Fehmi Rouba , Bar-Eli Menashe , Lee Ju-Seog , Ram Prahlad T. , Baggerly Keith A. , Lopez-Berestein Gabriel , Hung Mien-Chie , Sood Anil K. 
Published: April 2016

AbstractA deeper mechanistic understanding of tumour angiogenesis regulation is needed to improve current anti-angiogenic therapies. Here we present evidence from systems-based miRNA analyses of large-scale patient data sets along with in vitro and in vivo experiments that miR-192 is a key regulator of angiogenesis. The potent anti-angiogenic effect of miR-192 stems from its ability to globally downregulate angiogenic pathways in cancer cells through regulation of EGR1 and HOXB9. Low miR-192 expression in human tumours is predictive of poor clinical outcome in several cancer types. Using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes, we show that miR-192 delivery leads to inhibition of tumour angiogenesis in multiple ovarian and renal tumour models, resulting in tumour regression and growth inhibition. This anti-angiogenic and anti-tumour effect is more robust than that observed with an anti-VEGF antibody. Collectively, these data identify miR-192 as a central node in tumour angiogenesis and support the use of miR-192 in an anti-angiogenesis therapy.
Signature of coexistence of superconductivity and ferromagnetism in two-dimensional NbSe2 triggered by surface molecular adsorption
Authors: Zhu Xiaojiao , Guo Yuqiao , Cheng Hao , Dai Jun , An Xingda , Zhao Jiyin , Tian Kangzhen , Wei Shiqiang , Cheng Zeng Xiao , Wu Changzheng , Xie Yi 
Published: April 2016

AbstractFerromagnetism is usually deemed incompatible with superconductivity. Consequently, the coexistence of superconductivity and ferromagnetism is usually observed only in elegantly designed multi-ingredient structures in which the two competing electronic states originate from separate structural components. Here we report the use of surface molecular adsorption to induce ferromagnetism in two-dimensional superconducting NbSe2, representing the freestanding case of the coexistence of superconductivity and ferromagnetism in one two-dimensional nanomaterial. Surface-structural modulation of the ultrathin superconducting NbSe2 by polar reductive hydrazine molecules triggers a slight elongation of the covalent Nb–Se bond, which weakens the covalent interaction and enhances the ionicity of the tetravalent Nb with unpaired electrons, yielding ferromagnetic ordering. The induced ferromagnetic momentum couples with conduction electrons generating unique correlated effects of intrinsic negative magnetoresistance and the Kondo effect. We anticipate that the surface molecular adsorption will be a powerful tool to regulate spin ordering in the two-dimensional paradigm.
Prediction of a native ferroelectric metal
Authors: Filippetti Alessio , Fiorentini Vincenzo , Ricci Francesco , Delugas Pietro , Íñiguez Jorge 
Published: April 2016

AbstractOver 50 years ago, Anderson and Blount discussed symmetry-allowed polar distortions in metals, spawning the idea that a material might be simultaneously metallic and ferroelectric. While many studies have ever since considered such or similar situations, actual ferroelectricity—that is, the existence of a switchable intrinsic electric polarization—has not yet been attained in a metal, and is in fact generally deemed incompatible with the screening by mobile conduction charges. Here we refute this common wisdom and show, by means of first-principles simulations, that native metallicity and ferroelectricity coexist in the layered perovskite Bi5Ti5O17. We show that, despite being a metal, Bi5Ti5O17 can sustain a sizable potential drop along the polar direction, as needed to reverse its polarization by an external bias. We also reveal striking behaviours, as the self-screening mechanism at work in thin Bi5Ti5O17 layers, emerging from the interplay between polar distortions and carriers in this compound.
In situ microscopy of the self-assembly of branched nanocrystals in solution
Authors: Sutter Eli , Sutter Peter , Tkachenko Alexei V. , Krahne Roman , de Graaf Joost , Arciniegas Milena , Manna Liberato 
Published: April 2016

AbstractSolution-phase self-assembly of nanocrystals into mesoscale structures is a promising strategy for constructing functional materials from nanoscale components. Liquid environments are key to self-assembly since they allow suspended nanocrystals to diffuse and interact freely, but they also complicate experiments. Real-time observations with single-particle resolution could have transformative impact on our understanding of nanocrystal self-assembly. Here we use real-time in situ imaging by liquid-cell electron microscopy to elucidate the nucleation and growth mechanism and properties of linear chains of octapod-shaped nanocrystals in their native solution environment. Statistical mechanics modelling based on these observations and using the measured chain-length distribution clarifies the relative importance of dipolar and entropic forces in the assembly process and gives direct access to the interparticle interaction. Our results suggest that monomer-resolved in situ imaging combined with modelling can provide unprecedented quantitative insight into the microscopic processes and interactions that govern nanocrystal self-assembly in solution.
Legacy effects of short-term intentional weight loss on total body and thigh composition in overweight and obese older adults
Authors: Chmelo E A , Beavers D P , Lyles M F , Marsh A P , Nicklas B J , Beavers K M 
Published: April 2016

Abstract
Objective:
Weight regain following intentional weight loss may negatively impact body composition, accelerating fat regain and increasing risk of physical disability. The purpose of this study was to compare long-term changes in whole body and thigh composition in obese older adults who intentionally lost and then partially regained weight to obese older adults who remained weight stable.

Subjects/Methods:
This pilot study analyzed total body (dual-energy X-ray absorptiometry (DXA)) and thigh (computed tomography (CT)) composition data collected from 24 older (65–79 years) adults 18 months after completion of a 5-month randomized trial that compared resistance training alone (RT) with RT plus caloric restriction (RT+CR).

Results:
Mean loss of body mass in the RT+CR group (n=13) was 7.1±2.4 kg during the 5-month intervention (74% fat mass; 26% lean mass; all P<0.01), whereas RT (n=11) remained weight stable (+0.3±1.8 kg; P=0.64). Differential group effects were observed for all DXA and CT body composition measures at 5 months (all P⩽0.01); however, by 23 months, group differences persisted only for total body (RT+CR: 81.6±10.0 kg vs RT: 88.5±14.9 kg; P=0.03) and lean (RT+CR: 50.8±9.3 kg vs RT: 54.4±12.0 kg; P<0.01) mass. All RT+CR participants regained weight from 5 to 23 months (mean gain=+4.8±2.6 kg; P<0.01). Total fat mass and all thigh fat volumes increased, whereas thigh muscle volume decreased, during the postintervention follow-up in RT+CR (all P⩽0.01). In the RT group, body mass did not change from 5 to 23 months (−0.2±0.9 kg; P=0.87). Decreased total thigh volume, driven by the loss of thigh muscle volume, were the only postintervention body composition changes observed in the RT group (both P<0.04).

Conclusions:
Short-term body composition benefits of an RT+CR intervention may be lost within 18 months after completion of the intervention.
Ultraconserved region-containing Transformer 2β4 controls senescence of colon cancer cells
Authors: Kajita K , Kuwano Y , Satake Y , Kano S , Kurokawa K , Akaike Y , Masuda K , Nishida K , Rokutan K 
Published: April 2016

AbstractUltraconserved regions (UCRs) are >200 bp genomic segments with perfect human-to-rodent sequence identity. Transcribed UCRs constitute a new category of noncoding RNAs whose functions remain poorly understood. The human transformer 2β (TRA2B) gene contains a 419-bp UCR spanning the 276-bp exon 2 and its neighboring introns. TRA2B exon 2 has premature stop codons, whereas an exon 2-containing splice variant (TRA2β4) was expressed preferentially in the nuclei of human colon cancer cells. TRA2β4 knockdown p53-independently stimulated CDKN1A transcription and increased p21, resulting in the appearance of senescent cells. Biotin pull-down and RNA immunoprecipitation assays revealed that TRA2β4 interacted with Sp1 through a Sp1-binding sequence (485-GGGG-488) in a stem-loop structure of exon 2. Mutation of this sequence (485-AAGG-488) disrupted the stem-loop structure, blocked the interaction with Sp1 and increased CDKN1A transcription. Overexpression of TRA2β4 significantly decreased CDKN1A mRNA levels and accelerated cell growth, but the introduction of the mutation in the Sp1-binding sequence completely canceled these effects. Taken together, TRA2β4 may sequester Sp1 from occupying promoters of target genes including CDKN1A, promoting cell growth by interrupting the senescence-related gene expression program. This novel function of TRA2β4 may uncover an oncogenic function of transcribed UCRs.
BRCA1 positively regulates FOXO3 expression by restricting FOXO3 gene methylation and epigenetic silencing through targeting EZH2 in breast cancer
Authors: Gong C , Yao S , Gomes A R , Man E P S , Lee H J , Gong G , Chang S , Kim S-B , Fujino K , Kim S-W , Park S K , Lee J W , Lee M H ,   KOHBRA study group, Khoo U S , Lam E W-F 
Published: April 2016

AbstractBRCA1 mutation or depletion correlates with basal-like phenotype and poor prognosis in breast cancer but the underlying reason remains elusive. RNA and protein analysis of a panel of breast cancer cell lines revealed that BRCA1 deficiency is associated with downregulation of the expression of the pleiotropic tumour suppressor FOXO3. Knockdown of BRCA1 by small interfering RNA (siRNA) resulted in downregulation of FOXO3 expression in the BRCA1-competent MCF-7, whereas expression of BRCA1 restored FOXO3 expression in BRCA1-defective HCC70 and MDA-MB-468 cells, suggesting a role of BRCA1 in the control of FOXO3 expression. Treatment of HCC70 and MDA-MB-468 cells with either the DNA methylation inhibitor 5-aza-2'-deoxycitydine, the N-methyltransferase enhancer of zeste homologue 2 (EZH2) inhibitor GSK126 or EZH2 siRNA induced FOXO3 mRNA and protein expression, but had no effect on the BRCA1-competent MCF-7 cells. Chromatin immunoprecipitation (ChIP) analysis demonstrated that BRCA1, EZH2, DNMT1/3a/b and histone H3 lysine 27 trimethylation (H3K27me3) are recruited to the endogenous FOXO3 promoter, further advocating that these proteins interact to modulate FOXO3 methylation and expression. In addition, ChIP results also revealed that BRCA1 depletion promoted the recruitment of the DNA methyltransferases DNMT1/3a/3b and the enrichment of the EZH2-mediated transcriptional repressive epigenetic marks H3K27me3 on the FOXO3 promoter. Methylated DNA immunoprecipitation assays also confirmed increased CpG methylation of the FOXO3 gene on BRCA1 depletion. Analysis of the global gene methylation profiles of a cohort of 33 familial breast tumours revealed that FOXO3 promoter methylation is significantly associated with BRCA1 mutation. Furthermore, immunohistochemistry further suggested that FOXO3 expression was significantly associated with BRCA1 status in EZH2-positive breast cancer. Consistently, high FOXO3 and EZH2 mRNA levels were significantly associated with good and poor prognosis in breast cancer, respectively. Together, these data suggest that BRCA1 can prevent and reverse FOXO3 suppression via inhibiting EZH2 and, consequently, its ability to recruit the transcriptional repressive H3K27me3 histone marks and the DNA methylases DNMT1/3a/3b, to induce DNA methylation and gene silencing on the FOXO3 promoter.
The SMAC mimetic, LCL-161, reduces survival in aggressive MYC-driven lymphoma while promoting susceptibility to endotoxic shock
Authors: West A C , Martin B P , Andrews D A , Hogg S J , Banerjee A , Grigoriadis G , Johnstone R W , Shortt J 
Published: April 2016

AbstractInhibitor of apoptosis proteins (IAPs) antagonize caspase activation and regulate death receptor signaling cascades. LCL-161 is a small molecule second mitochondrial activator of caspase (SMAC) mimetic, which both disengages IAPs from caspases and induces proteasomal degradation of cIAP-1 and -2, resulting in altered signaling through the NFκB pathway, enhanced TNF production and sensitization to apoptosis mediated by the extrinsic pathway. SMAC mimetics are undergoing clinical evaluation in a range of hematological malignancies. Burkitt-like lymphomas are hallmarked by a low apoptotic threshold, conveying sensitivity to a range of apoptosis-inducing stimuli. While evaluating LCL-161 in the Eμ-Myc model of aggressive Burkitt-like lymphoma, we noted unexpected resistance to apoptosis induction despite ‘on-target’ IAP degradation and NFκB activation. Moreover, LCL-161 treatment of lymphoma-bearing mice resulted in apparent disease acceleration concurrent to augmented inflammatory cytokine-release in the same animals. Indiscriminate exposure of lymphoma patients to SMAC mimetics may therefore be detrimental due to both unanticipated prolymphoma effects and increased susceptibility to endotoxic shock.
Dcc Mediates Functional Assembly of Peripheral Auditory Circuits
Authors: Kim Young J. , Wang Sheng-zhi , Tymanskyj Stephen , Ma Le , Tao Huizhong W. , Zhang Li I. 
Published: April 2016

AbstractProper structural organization of spiral ganglion (SG) innervation is crucial for normal hearing function. However, molecular mechanisms underlying the developmental formation of this precise organization remain not well understood. Here, we report in the developing mouse cochlea that deleted in colorectal cancer (Dcc) contributes to the proper organization of spiral ganglion neurons (SGNs) within the Rosenthal’s canal and of SGN projections toward both the peripheral and central auditory targets. In Dcc mutant embryos, mispositioning of SGNs occurred along the peripheral auditory pathway with misrouted afferent fibers and reduced synaptic contacts with hair cells. The central auditory pathway simultaneously exhibited similar defective phenotypes as in the periphery with abnormal exit of SGNs from the Rosenthal’s canal towards central nuclei. Furthermore, the axons of SGNs ascending into the cochlear nucleus had disrupted bifurcation patterns. Thus, Dcc is necessary for establishing the proper spatial organization of SGNs and their fibers in both peripheral and central auditory pathways, through controlling axon targeting and cell migration. Our results suggest that Dcc plays an important role in the developmental formation of peripheral and central auditory circuits and its mutation may contribute to sensorineural hearing loss.