bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymmetric ring structure of Vps4 required for ESCRT-III disassembly
Authors: Caillat Christophe , Macheboeuf Pauline , Wu Yuanfei , McCarthy Andrew A. , Boeri-Erba Elisabetta , Effantin Gregory , Göttlinger Heinrich G. , Weissenhorn Winfried , Renesto Patricia 
Published: December 2015

AbstractThe vacuolar protein sorting 4 AAA–ATPase (Vps4) recycles endosomal sorting complexes required for transport (ESCRT-III) polymers from cellular membranes. Here we present a 3.6-Å X-ray structure of ring-shaped Vps4 from Metallosphera sedula (MsVps4), seen as an asymmetric pseudohexamer. Conserved key interface residues are shown to be important for MsVps4 assembly, ATPase activity in vitro, ESCRT-III disassembly in vitro and HIV-1 budding. ADP binding leads to conformational changes within the protomer, which might propagate within the ring structure. All ATP-binding sites are accessible and the pseudohexamer binds six ATP with micromolar affinity in vitro. In contrast, ADP occupies one high-affinity and five low-affinity binding sites in vitro, consistent with conformational asymmetry induced on ATP hydrolysis. The structure represents a snapshot of an assembled Vps4 conformation and provides insight into the molecular motions the ring structure undergoes in a concerted action to couple ATP hydrolysis to ESCRT-III substrate disassembly.
Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection
Authors: Zuo Teng , Sun Jianfeng , Wang Guiqin , Jiang Liwei , Zuo Yanan , Li Danyang , Shi Xuanling , Liu Xi , Fan Shilong , Ren Huanhuan , Hu Hongxing , Sun Lina , Zhou Boping , Liang Mifang , Zhou Paul , Wang Xinquan , Zhang Linqi 
Published: December 2015

AbstractUnderstanding the mechanism of protective antibody recognition against highly pathogenic avian influenza A virus H5N1 in humans is critical for the development of effective therapies and vaccines. Here we report the crystal structure of three H5-specific human monoclonal antibodies bound to the globular head of hemagglutinin (HA) with distinct epitope specificities, neutralization potencies and breadth. A structural and functional analysis of these epitopes combined with those reported elsewhere identifies four major vulnerable sites on the globular head of H5N1 HA. Chimeric and vulnerable site-specific mutant pseudoviruses are generated to delineate broad neutralization specificities of convalescent sera from two individuals who recovered from the infection with H5N1 virus. Our results show that the four vulnerable sites on the globular head rather than the stem region are the major neutralizing targets, suggesting that during natural H5N1 infection neutralizing antibodies against the globular head work in concert to provide protective antibody-mediated immunity.
Mica Nanoparticle, STB-HO Eliminates the Human Breast Carcinoma Cells by Regulating the Interaction of Tumor with its Immune Microenvironment
Authors: Kang Tae-Wook , Kim Hyung-Sik , Lee Byung-Chul , Shin Tae-Hoon , Choi Soon Won , Kim Yoon-Jin , Lee Hwa-Yong , Jung Yeon-Kwon , Seo Kwang-Won , Kang Kyung-Sun 
Published: December 2015

AbstractMica, an aluminosilicate mineral, has been proven to possess anti-tumor and immunostimulatory effects. However, its efficacy and mechanisms in treating various types of tumor are less verified and the mechanistic link between anti-tumor and immunostimulatory effects has not been elucidated. We sought to investigate the therapeutic effect of STB-HO (mica nanoparticles) against one of the most prevalent cancers, the breast cancer. STB-HO was orally administered into MCF-7 xenograft model or directly added to culture media and tumor growth was monitored. STB-HO administration exhibited significant suppressive effects on the growth of MCF-7 cells in vivo, whereas STB-HO did not affect the proliferation and apoptosis of MCF-7 cells in vitro. To address this discrepancy between in vivo and in vitro results, we investigated the effects of STB-HO treatment on the interaction of MCF-7 cells with macrophages, dendritic cells (DCs) and natural killer (NK) cells, which constitute the cellular composition of tumor microenvironment. Importantly, STB-HO not only increased the susceptibility of MCF-7 cells to immune cells, but also stimulated the immunocytes to eliminate cancer cells. In conclusion, our study highlights the possible role of STB-HO in the suppression of MCF-7 cell growth via the regulation of interactions between tumor cells and anti-tumor immune cells.
The isolation and characterization of CTC subsets related to breast cancer dormancy
Authors: Vishnoi Monika , Peddibhotla Sirisha , Yin Wei , T. Scamardo Antonio , George Goldy C. , Hong David S. , Marchetti Dario 
Published: December 2015

AbstractUncovering CTCs phenotypes offer the promise to dissect their heterogeneity related to metastatic competence. CTC survival rates are highly variable and this can lead to many questions as yet unexplored properties of CTCs responsible for invasion and metastasis vs dormancy. We isolated CTC subsets from peripheral blood of patients diagnosed with or without breast cancer brain metastasis. CTC subsets were selected for EpCAM negativity but positivity for CD44+/CD24− stem cell signature; along with combinatorial expression of uPAR and int β1, two markers directly implicated in breast cancer dormancy mechanisms. CTC subsets were cultured in vitro generating 3D CTC tumorspheres which were interrogated for biomarker profiling and biological characteristics. We identified proliferative and invasive properties of 3D CTC tumorspheres distinctive upon uPAR/int β1 combinatorial expression. The molecular characterization of uPAR/int β1 CTC subsets may enhance abilities to prospectively identify patients who may be at high risk of developing BCBM.
Incorporating Contact Network Structure in Cluster Randomized Trials
Authors: Staples Patrick C. , Ogburn Elizabeth L. , Onnela Jukka-Pekka 
Published: December 2015

AbstractWhenever possible, the efficacy of a new treatment is investigated by randomly assigning some individuals to a treatment and others to control and comparing the outcomes between the two groups. Often, when the treatment aims to slow an infectious disease, clusters of individuals are assigned to each treatment arm. The structure of interactions within and between clusters can reduce the power of the trial, i.e. the probability of correctly detecting a real treatment effect. We investigate the relationships among power, within-cluster structure, cross-contamination via between-cluster mixing and infectivity by simulating an infectious process on a collection of clusters. We demonstrate that compared to simulation-based methods, current formula-based power calculations may be conservative for low levels of between-cluster mixing, but failing to account for moderate or high amounts can result in severely underpowered studies. Power also depends on within-cluster network structure for certain kinds of infectious spreading. Infections that spread opportunistically through highly connected individuals have unpredictable infectious breakouts, making it harder to distinguish between random variation and real treatment effects. Our approach can be used before conducting a trial to assess power using network information and we demonstrate how empirical data can inform the extent of between-cluster mixing.
Differential evolution of a CXCR4-using HIV-1 strain in CCR5wt/wt and CCR5∆32/∆32 hosts revealed by longitudinal deep sequencing and phylogenetic reconstruction
Authors: Le Anh Q. , Taylor Jeremy , Dong Winnie , McCloskey Rosemary , Woods Conan , Danroth Ryan , Hayashi Kanna , Milloy M.-J. , Poon Art F. Y. , Brumme Zabrina L. 
Published: December 2015

AbstractRare individuals homozygous for a naturally-occurring 32 base pair deletion in the CCR5 gene (CCR5∆32/∆32) are resistant to infection by CCR5-using (“R5”) HIV-1 strains but remain susceptible to less common CXCR4-using (“X4”) strains. The evolutionary dynamics of X4 infections however, remain incompletely understood. We identified two individuals, one CCR5wt/wt and one CCR5∆32/∆32, within the Vancouver Injection Drug Users Study who were infected with a genetically similar X4 HIV-1 strain. While early-stage plasma viral loads were comparable in the two individuals (~4.5–5 log10 HIV-1 RNA copies/ml), CD4 counts in the CCR5wt/wt individual reached a nadir of <20 CD4 cells/mm3 within 17 months but remained >250 cells/mm3 in the CCR5∆32/∆32 individual. Ancestral phylogenetic reconstructions using longitudinal envelope-V3 deep sequences suggested that both individuals were infected by a single transmitted/founder (T/F) X4 virus that differed at only one V3 site (codon 24). While substantial within-host HIV-1 V3 diversification was observed in plasma and PBMC in both individuals, the CCR5wt/wt individual’s HIV-1 population gradually reverted from 100% X4 to ~60% R5 over ~4 years whereas the CCR5∆32/∆32 individual’s remained consistently X4. Our observations illuminate early dynamics of X4 HIV-1 infections and underscore the influence of CCR5 genotype on HIV-1 V3 evolution.
Assimilation of the seabird and ship drift data in the north-eastern sea of Japan into an operational ocean nowcast/forecast system
Authors: Miyazawa Yasumasa , Guo Xinyu , Varlamov Sergey M. , Miyama Toru , Yoda Ken , Sato Katsufumi , Kano Toshiyuki , Sato Keiji 
Published: December 2015

AbstractAt the present time, ocean current is being operationally monitored mainly by combined use of numerical ocean nowcast/forecast models and satellite remote sensing data. Improvement in the accuracy of the ocean current nowcast/forecast requires additional measurements with higher spatial and temporal resolution as expected from the current observation network. Here we show feasibility of assimilating high-resolution seabird and ship drift data into an operational ocean forecast system. Data assimilation of geostrophic current contained in the observed drift leads to refinement in the gyre mode events of the Tsugaru warm current in the north-eastern sea of Japan represented by the model. Fitting the observed drift to the model depends on ability of the drift representing geostrophic current compared to that representing directly wind driven components. A preferable horizontal scale of 50 km indicated for the seabird drift data assimilation implies their capability of capturing eddies with smaller horizontal scale than the minimum scale of 100 km resolved by the satellite altimetry. The present study actually demonstrates that transdisciplinary approaches combining bio-/ship- logging and numerical modeling could be effective for enhancement in monitoring the ocean current.
Comprehensive analysis of lncRNA-mRNA co-expression patterns identifies immune-associated lncRNA biomarkers in ovarian cancer malignant progression
Authors: Guo Qiuyan , Cheng Yan , Liang Tian , He Yanan , Ren Chengcheng , Sun Liyuan , Zhang Guangmei 
Published: December 2015

AbstractOvarian cancer (OV) is the most common and lethal gynecological tumor with a poor prognosis for women; however, the regulatory roles of the long non-coding RNAs (lncRNAs) in ovarian malignant progression are insufficiently understood. Here, we investigated the expression patterns of lncRNAs and mRNAs in the high-throughput molecular profiles of 399 OV patients and constructed a functional lncRNA-mRNA co-expression network across OV malignant progression. We found that two protective lncRNAs, RP11-284N8.3.1 and AC104699.1.1, were not only differentially expressed throughout the progression of malignant OV but were also independently predictive of the survival of patients with different OV stages. A functional analysis of the two lncRNAs predicted their roles in immune system activation and other anti-tumor processes in the OV microenvironment. Integrating these two lncRNAs into an OV risk model was able to significantly stratify patients into different risk groups. Overall, our analysis effectively provides insights into the lncRNA association with malignant OV progression. The two-lncRNA signature is a candidate biomarker for the prognosis of patients with OV and may enable a more accurate prediction of survival.
Laser-tuned whispering gallery modes in a solid-core microstructured optical fibre integrated with magnetic fluids
Authors: Lin Wei , Zhang Hao , Liu Bo , Song Binbin , Li Yuetao , Yang Chengkun , Liu Yange 
Published: December 2015

AbstractA laser-assisted tuning method of whispering gallery modes (WGMs) in a cylindrical microresonator based on magnetic-fluids-infiltrated microstructured optical fibres (MFIMOFs, where MF and MOF respectively refer to magnetic fluid and microstructured optical fibre) is proposed, experimentally demonstrated and theoretically analysed in detail. The MFIMOF is prepared by infiltrating the air-hole array of the MOF using capillary action effect. A fibre-coupling system is set up for the proposed MFIMOF-based microresonator to acquire an extinction ratio up to 25 dB and a Q-factor as large as 4.0 × 104. For the MF-infiltrated MOF, the light propagating in the fibre core region would rapidly spread out and would be absorbed by the MF-rod array cladding to induce significant thermal effect. This has been exploited to achieve a WGM resonance wavelength sensitivity of 0.034 nm/mW, which is ~20 times higher than it counterpart without MF infiltration. The wavelength response of the resonance dips exhibit linear power dependence and owing to such desirable merits as ease of fabrication, high sensitivity and laser-assisted tunability, the proposed optical tuning approach of WGMs in the MFIMOF would find promising applications in the areas of optical filtering, sensing and signal processing, as well as future all-optical networking systems.
Aluminium alloyed iron-silicide/silicon solar cells: A simple approach for low cost environmental-friendly photovoltaic technology
Authors: Kumar Dalapati Goutam , Masudy-Panah Saeid , Kumar Avishek , Cheh Tan Cheng , Ru Tan Hui , Chi Dongzhi 
Published: December 2015

AbstractThis work demonstrates the fabrication of silicide/silicon based solar cell towards the development of low cost and environmental friendly photovoltaic technology. A heterostructure solar cells using metallic alpha phase (α-phase) aluminum alloyed iron silicide (FeSi(Al)) on n-type silicon is fabricated with an efficiency of 0.8%. The fabricated device has an open circuit voltage and fill-factor of 240 mV and 60%, respectively. Performance of the device was improved by about 7 fold to 5.1% through the interface engineering. The α-phase FeSi(Al)/silicon solar cell devices have promising photovoltaic characteristic with an open circuit voltage, short-circuit current and a fill factor (FF) of 425 mV, 18.5 mA/cm2 and 64%, respectively. The significant improvement of α-phase FeSi(Al)/n-Si solar cells is due to the formation p+−n homojunction through the formation of re-grown crystalline silicon layer (~5–10 nm) at the silicide/silicon interface. Thickness of the regrown silicon layer is crucial for the silicide/silicon based photovoltaic devices. Performance of the α-FeSi(Al)/n-Si solar cells significantly depends on the thickness of α-FeSi(Al) layer and process temperature during the device fabrication. This study will open up new opportunities for the Si based photovoltaic technology using a simple, sustainable and los cost method.
Anti-sense DNA d(GGCCCC)n expansions in C9ORF72 form i-motifs and protonated hairpins
Authors: Kovanda Anja , Zalar Matja , Šket Primož , Plavec Janez , Rogelj Boris 
Published: December 2015

AbstractThe G4C2 hexanucleotide repeat expansion mutation (HREM) in C9ORF72, represents the most common mutation associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Three main disease mechanisms have been proposed to date: C9ORF72 haploinsufficiency, RNA toxicity and accumulation of dipeptide repeat proteins. Pure GC content of the HREM potentially enables the formation of various non-B DNA structures such as G-quadruplexes and i-motifs. These structures are proposed to act as promoters and regulatory elements affecting replication, transcription and translation of the surrounding region. G-quadruplexes have already been shown on the G-rich sense DNA and RNA strands (G4C2)n, the structure of the anti-sense (G2C4)n strand remains unresolved. Similar C-rich sequences may, under acidic conditions, form i-motifs consisting of two parallel duplexes in a head to tail orientation held together by hemi-protonated C+-C pairs. We show that d(G2C4)n repeats do form i-motif and protonated hairpins even under near-physiological conditions. Rather than forming a DNA duplex, i-motifs persist even in the presence of the sense strand. This preferential formation of G-quadruplex and i-motif/hairpin structures over duplex DNA, may explain HREM replicational and transcriptional instability. Furthermore, i-motifs/hairpins can represent a novel pharmacological target for C9ORF72 associated ALS and FTLD.
Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21
Authors: Zhang Cuiyan , Li Xiaotong , Adelmant Guillaume , Dobbins Jessica , Geisen Christoph , Oser Matthew G. , Wucherpfenning Kai W. , Marto Jarrod A. , Kaelin William G. 
Published: December 2015

SignificanceMany short-lived proteins perform important cellular functions that must be tightly regulated. EID1 is an unstable protein implicated in the control of transcription, differentiation, and genomic integrity. EID1 is particularly unstable in G0 cells. Here we show that an SCF complex containing the orphan F-box only protein FBXO21 is the ubiquitin ligase that recognizes EID1 in both cycling and G0 cells and that it recognizes a modular, peptidic domain within EID1. This degron overlaps with the EID1 region that binds to the retinoblastoma tumor suppressor protein (pRB) and to melanoma-associated antigen (MAGE) proteins, suggesting that multiple proteins compete for binding to EID1 and secondarily influence its ubiquitinylation. This study sheds light on the regulation of EID1, the function of FBXO21, and control of protein turnover by ubiquitin ligases.
Beyond Fab Four
Authors: Babichev E , Charmousis C , Langlois D , Saito R 
Published: December 2015

Abstract
We show that the two additional Lagrangians that appear in theories beyond Horndeski can be reexpressed in terms of simple generalizations of the ‘John’ and ‘Paul’ terms of the Fab Four theories. We find that these extended Fab Four satisfy the same properties of self-tuning as the original Fab Four.
LoCuSS: Testing hydrostatic equilibrium in galaxy clusters
Authors: Smith G. P. , Mazzotta P. , Okabe N. , Ziparo F. , Mulroy S. L. , Babul A. , Finoguenov A. , McCarthy I. G. , Lieu M. , Bahé Y. M. , Bourdin H. , Evrard A. E. , Futamase T. , Haines C. P. , Jauzac M. , Marrone D. P. , Martino R. , May P. E. , Taylor J. E. , Umetsu K. 
Published: December 2015

Abstract
We test the assumption of hydrostatic equilibrium in an X-ray luminosity selected sample of 50 galaxy clusters at 0.15 &lt; z &lt; 0.3 from the Local Cluster Substructure Survey (LoCuSS). Our weak-lensing measurements of M500 control systematic biases to sub-4 per cent, and our hydrostatic measurements of the same achieve excellent agreement between XMM–Newton and Chandra. The mean ratio of X-ray to lensing mass for these 50 clusters is $\mathrel {\beta _{\rm X}}\;= 0.95\pm 0.05$, and for the 44 clusters also detected by Planck, the mean ratio of Planck mass estimate to LoCuSS lensing mass is $\mathrel {\beta _{\rm P}}\;= 0.95\pm 0.04$. Based on a careful like-for-like analysis, we find that LoCuSS, the Canadian Cluster Comparison Project, and Weighing the Giants agree on $\mathrel {\beta _{\rm P}}\;\simeq 0.9{\rm -}0.95$ at 0.15 &lt; z &lt; 0.3. This small level of hydrostatic bias disagrees at ∼5σ with the level required to reconcile Planck cosmology results from the cosmic microwave background and galaxy cluster counts.
Long-term Results After Extensive Soft Tissue Release in Very Severe Congenital Clubfeet
Authors: Alkar Fanny , Louahem Djamel , Bonnet Frédérique , Patte Karine , Delpont Marion , Cottalorda Jérôme 
Published: December 2015

Background:
The purpose of this study was to determine the long-term results, at an average follow-up of 22 years, in 66 patients (105 clubfeet) with very severe congenital idiopathic clubfeet according to the Dimeglio-Bensahel scale.

Methods:
Patients were treated with an extensive soft tissue release in infancy. Results of the treatment were assessed according to the 100-point system of Ghanem-Seringe. At the latest follow-up, all participants were evaluated with regard to pain and the overall function of the lower extremities. At the latest follow-up, anteroposterior and lateral radiographs of the affected foot and the contralateral normal foot, when applicable, were performed.

Results:
In total, 92% of the patients were satisfied. The mean functional score of Ghanem-Seringe was 70.4 points. No foot had an excellent result, 19 feet had a good result, 16 had a fair result, and 70 had a poor result. A total of 86 feet were painful after strenuous activities or during walking. Eleven patients walked with a limp. In total, 82 feet were stiff. Ankle dorsiflexion and plantar flexion averaged 4.0±4.5 degrees and 19.9±10.7 degrees. Bone deformations such as flattening of the talar dome were observed in 93 feet. Among these feet, the Ghanem score was significantly lower (P<0.05). Necrosis of the navicular was present in 28 feet and subluxation in 82 feet. In total, 32 feet had moderate osteoarthritis.

Discussion:
Results revealed that despite anatomically and radiologically imperfect clubfeet, most patients demonstrated satisfaction. Satisfaction was not significantly correlated with residual deformity, but with the sensation of a normal gait by the patient and the high initial Dimeglio-Bensahel score. Female patients were significantly less satisfied than male patients because they were more constrained in their social life than boys. Their main dissatisfaction was the atrophy of the calf. We noted several residual deformations. Plantar release seems to contribute to the high rate of overcorrection in our series. Extensive posterolateral and plantar releases in very severe clubfeet was responsible for sequelae, morphologic, anatomic, and functional, especially in adulthood. Deterioration of results over time was confirmed by our series.

Level of Evidence:
Level IV.