Miracle-dz/UniFAR-FTUs huggingface dataset:
Icariin, but Not Genistein, Exerts Osteogenic and Anti-apoptotic Effects in Osteoblastic Cells by Selective Activation of Non-genomic ERα Signaling

Genistein and icariin are flavonoid compounds that exhibit estrogen-like properties in inducing bone formation and reducing bone loss associated with estrogen deficiency in both preclinical and clinical studies. However, the mechanisms that are involved in mediating their estrogenic actions in bone cells are far from clear. The present study aimed to study the signaling pathways that mediate the estrogenic actions of genistein and icariin in osteoblastic cells. The effects of genistein and icariin on the activation of estrogen receptor (ER) and the downstream mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in murine osteoblastic MC3T3-E1 cells and rat osteoblastic UMR-106 cells were studied. As expected, genistein displayed higher binding affinity toward ERβ than ERα and significantly induced estrogen response element (ERE)-dependent transcription in UMR-106 cells in a dose-dependent manner. In contrast, icariin failed to bind to ERα or ERβ and did not induce ERE-dependent transcription in UMR-106 cells at 10-10 to 10-7 M. The effects of genistein (10 nM) and icariin (0.1 μM) on cell proliferation and differentiation in osteoblastic UMR-106 cells were abolished in the presence of ER antagonist ICI 182,780 (1 μM), MAPK inhibitor U0126 (10 μM), and PI3K inhibitor LY294002 (10 μM). Genistein at 10 nM rapidly induced ERK1/2 phosphorylation at 5–10 min in UMR-106 cells and the phosphorylation of ERα at both Ser118 and Ser167 in both MC3T3-E1 and transfected UMR-106 cells whereas icariin at 0.1 μM rapidly activated both ERK1/2 and Akt phosphorylation in UMR-106 cells and subsequent ERα phosphorylation at both Ser118 and Ser167 in MC3T3-E1 and transfected UMR-106 cells. Confocal imaging studies confirmed that the phosphorylation of ERα at Ser 118 and Ser 167 by genistein and icariin in MC3T3-E1 cells was mediated via MAPK- and PI3K-dependent pathway, respectively. Furthermore, our studies showed that icariin exerted stronger anti-apoptotic effects than genistein and 17β-estradiol (E2) and inhibited the cleavage of downstream caspase-3 in MC3T3-E1 cells induced by a potent PI3K inhibitor, PI828 (at 2 μM). These results indicated that the mechanisms that mediate the estrogenic actions of icariin in osteoblastic cells are different from those of genistein.
Stream: Decentralized opportunistic inter-coflow scheduling for datacenter networks

Coflow scheduling can improve application-level communication performance for data-parallel clusters. However, most prior coflow scheduling schemes are based on the centralized approach, which achieve good performance but suffers from high control overhead and scalability issue. On the other hand, state of the art decentralized solution requires switch modification, which makes it hard to implement. In this paper, we present Stream, the decentralized and readilyimplementable solution for coflow scheduling. The key idea of Stream is to opportunistically take advantage of many-to-one and many-to-many coflow patterns to coordinate coflows without resorting to the centralized controller, and then emulate shortest coflow first scheduling to minimize the average coflow completion time (CCT). We implement Stream with existing commodity switches and show its performance using both testbed experiments and large-scale simulations. Our evaluation results show that Stream's performance is comparable to the centralized solution, and outperforms the state of the art decentralized scheme by 1.77x on average.
The Process of Writing Research Articles in English and Getting Published: A Case Study

Anadili Ingilizce olmayan ve Ingilizce yazmak zorunda olan akademisyenlerin makalelerini indekslerde taranan dergilerde yayinlatmalari, onlarin oldukca uzun ve zor bir surecten gecmelerini gerektirir. Bu calismada, Ingilizceyi yabanci dil olarak kullanan dort Turk akademisyenle (iki fizikci, iki insat muhendisi) gorustuk ve Ingilizce makale yazarken ve onlari yayinlatmaya calisirken icinden gectikleri surecleri analiz ettik. Ingilizce dergilerde makale yayinlatmanin zorluklari hakkinda daha fazla ic goru kazanmak icin indekslerde taranan dergilerde yayinlanmis makalesi olmayan dort akademisyen (bir tarihci, bir dilbilimci, bir sosyolog ve bir egitim bilimci) ile daha gorusme yaptik. Turk universitelerinde docentlik kadrosu alabilmek icin, akademisyenlerin indekslerde taranan ve cogu Ingilizce olan dergilerde makale yayinlatmalari bir zorunluluktur. Ancak bu surec, Amerika Birlesik Devletleri’nde ya da Ingiltere’de uzun sure bulunmamis ve yazma konusunda herhangi bir formal egitim almamis akademisyenler icin cok daha zordur. Yaptigimiz gorusmeler ve gozlem sureci, fen ve muhendislik alanlarinda yayinlanan makalelerin onceden yerlesmis kurallar ve kaliplar cercevesinde yazildigini, bu alanlarda makale yazmanin mekanik bir surec gibi algilandigini ve bu yuzden da sosyal bilimlerle ilgili makalelerden daha kolay yazilip yayinlandigini gostermektedir
Electron acceptor availability alters carbon and energy metabolism in a thermoacidophile

The thermoacidophilic Acidianus strain DS80 displays versatility in its energy metabolism and can grow autotrophically and heterotrophically with elemental sulfur (S°), ferric iron (Fe3+ ) or oxygen (O2 ) as electron acceptors. Here, we show that autotrophic and heterotrophic growth with S° as the electron acceptor is obligately dependent on hydrogen (H2 ) as electron donor; organic substrates such as acetate can only serve as a carbon source. In contrast, organic substrates such as acetate can serve as electron donor and carbon source for Fe3+ or O2 grown cells. During growth on S° or Fe3+ with H2 as an electron donor, the amount of CO2 assimilated into biomass decreased when cultures were provided with acetate. The addition of CO2 to cultures decreased the amount of acetate mineralized and assimilated and increased cell production in H2 /Fe3+ grown cells but had no effect on H2 /S° grown cells. In acetate/Fe3+ grown cells, the presence of H2 decreased the amount of acetate mineralized as CO2 in cultures compared to those without H2 . These results indicate that electron acceptor availability constrains the variety of carbon sources used by this strain. Addition of H2 to cultures overcomes this limitation and alters heterotrophic metabolism.
Liposomes derivatized with multimeric copies of KCCYSL peptide as targeting agents for HER-2-overexpressing tumor cells

Mixed liposomes, obtained by coaggregation of 1,2-dioleoyl-sn-glycero-3-phosphocholine and of the synthetic monomer containing a gadolinium complex ([C18]2DTPA[Gd]) have been prepared. Liposomes externally decorated with KCCYSL (P6.1 peptide) sequence in its monomeric, dimeric, and tetrameric forms are studied as target-selective delivery systems toward cancer cells overexpressing human epidermal growth factor receptor-2 (HER-2) receptors. Derivatization of liposomal surface with targeting peptides is achieved using the postmodification method: the alkyne-peptide derivative Pra-KCCYSL reacts, through click chemistry procedures, with a synthetic surfactant modified with 1, 2, or 4 azido moieties previously inserted in liposome formulation. Preliminary in vitro data on MDA-MB-231 and BT-474 cells indicated that liposomes functionalized with P6.1 peptide in its tetrameric form had better binding to and uptake into BT-474 cells compared to liposomes decorated with monomeric or dimeric versions of the P6.1 peptide. BT-474 cells treated with liposomes functionalized with the tetrameric form of P6.1 showed high degree of liposome uptake, which was comparable with the uptake of anti-HER-2 antibodies such as Herceptin. Moreover, magnetic MRI experiments have demonstrated the potential of liposomes to act as MRI contrast agents.
The new economy as a gateway to leisure travelling: experiences of highly skilled Indian professionals in Europe

Abstract This article investigates India’s professionals’ tourist mobilities during on-site assignments in continental Europe. The concept of experiential cultural capital is introduced to highlight the sociocultural symbolic significance of experiences of travelling for leisure enabled by one’s professional career. The study (conducted between 2007 and 2013) is based on ethnographic research online and in-depth face-to-face interviews with 76 Indian expatriates working in the information, communication and technology (ICT) sector in Brussels. This complementary approach of online and offline research enabled the observation of practices of status distinction, which deepened the understanding of Indian professionals’ tourist mobility. The data of the lived experiences of leisure travelling enabled by professional career trajectories illustrate practices of capital accumulation. In addition, they show how India’s youth, inscribed in new economy sectors, such as the ICT sector, seize the volatile opportunities offered by changing global economic and political conditions. Moreover, this research indicates how occupational identity is intertwined with particular practices of leisure travelling as the organisational culture might influence leisure opportunities. Therefore, by participating in and managing this symbolic resource of tourist mobility, professionals signal their economic success to their family and peers in order to be recognised as such.
Ceritinib Enhances the Efficacy of Substrate Chemotherapeutic Agent in Human ABCB1-Overexpressing Leukemia Cells In Vitro, In Vivo and Ex-Vivo

Background/Aims: Multidrug resistance (MDR) triggered by ATP binding cassette (ABC) transporters, such as ABCB1, ABCC1, and ABCG2, is a key obstacle for successful cancer chemotherapy. There is currently no FDA-approved MDR modulator that can be used in clinic. Ceritinib, a selective ALK inhibitor, has been approved as the second-line treatment for ALK-positive non-small cell lung cancer. Here, we examined the role of ceritinib in leukemia associated MDR in therapy. Methods: The cell proliferation was detected by MTT assay. The flow cytometry was used to detect the expression of cell surface protein and to detect the accumulation and efflux of rhodamine 123 (Rh123) or doxorubicin (Dox) in cells. The RT-PCR and Western blot were performed to detect the gene expression and protein expression levels, respectively. Results: We found that ceritinib enhanced the efficacy of substrate chemotherapeutic agent in ABCB1-overexpressing K562/adr leukemia cells both in vitro and in vivo models, but neither in sensitive parental K562 leukemia cells nor in ABCC1-overexpressing HL-60/adr leukemia cells. Mechanistically, ceritinib significantly increased the intracellular accumulation of Rh123 or Dox but did neither alter ABCB1 expressions at both protein and mRNA levels nor block the phosphorylations of AKT and ERK1/2 at the concentration of MDR reversal. Importantly, ceritinib also increased the intracellular accumulation of Dox and enhanced the efficacy of Dox in primary leukemia cells in ex-vivo. Conclusion: Our results suggested that ceritinib enhanced the efficacy of substrate chemotherapeutic agent on inhibition of leukemia cell growth in vitro, in vivo and ex-vivo, which linked to block ABCB1 function, pumping out its substrate conventional chemotherapeutic agent, thereby increasing the intracellular accumulation. These suggest the combination of ceritinib and substrate chemotherapeutic drugs maybe an effective treatment of resistant leukemia patients with ABCB1-mediated MDR.
Does the increased hydrophobicity of the interior and hydrophilicity of the exterior of an enzyme structure reflect its increased thermostability ?

The values of hydrophobicity of internal and external elements of the secondary structure of three Bacillus ~-amylase (fl~)s barrel domains have been calculated in order to investigate whether there is some correlation between the values and the enzyme stability. All the values have been referred to the number of amino acids in the oiven fl-sheet or ~-helix to eliminate the differences caused by non-equal length of the sheet or helix. Hydrophobicity units obtained have been averaged according to the number of internal (all [l-strands and helix ~7) and external (helices ctl-~6 and ~8) elements of secondary structure of the ~-amylase ([i~)a barrel. The averaged hydrophobicity units have been found to correlate with the thermal stability of the three Bacillus ~-amylases in terms of the increased hydrophobicity of the interior as well as the increased hydrophilicity of the exterior of the (fl~)a barrel domain for the ~-amylase with increased thermostability.
Simulations and experiments showing the origin of multiwavelength mode locking in femtosecond, Yb-fiber lasers

A stable and self-starting femtosecond breathing-pulse Yb-fiber oscillator is reported, modelocked using the nonlinear polarisation evolution mechanism. A bifurcation between two distinct modes of operation is demonstrated experimentally, producing pulses with a single central wavelength in one state, or following adjustment of the intra-cavity waveplates, the emission of pulses with three distinct central wavelengths. The maximum bandwidth was 72 nm at the -10 dB level and the pulses were compressible externally to 70 fs with energies of 0.75 nJ. The multi-wavelength pulses reported here are significantly shorter than the pico-second pulses previously observed from similar modelocked multi-wavelength sources. Vector simulations based on the nonlinear Schrodinger equation show that the multi-wavelength behaviour is produced by overdriving the nonlinear polarisation evolution based saturable absorber at the peak of the pulse, leading to transmission of the two wings of the strongly chirped pulse. This new insight shows clearly that the three pulses output in the multi-wavelength state are coherent. The agreement between simulation and experimental data shows nonlinear polarisation evolution based modelocked fiber lasers are a suitable platform for studying the nonlinear dynamics underlying the bifurcation of the output.
Drug-coated balloon in superficial femoral artery in-stent restenosis

The femoropopliteal artery is one of the commonest sites of involvement in peripheral artery disease (PAD) leading to intermittent claudication and/or critical limb ischemia. Endovascular therapy for superficial femoral artery (SFA) disease has been recognized as a safe and efficient therapy and is recommended by current guidelines as the first-line approach. Although the widespread use of new-generation, self-expanding, nitinol stents in SFA stenosis has reduced the shortcomings associated with plain old balloon angioplasty (POBA), lumen renarrowing at the stented (in-stent restenosis – ISR) level still represents a relevant clinical problem, because of higher risk of recurrent ISR, occlusion and surgical revascularization compared to de-novo lesions. In this setting, different treatment options are available and drug-coated balloons (DCBs) have shown good results in terms of safety and effectiveness. In this review we examine the results of different trials exploring the outcome of using DCBs for the treatment of SFA ISR. The available data demonstrate that SFA ISR can be safely treated with percutaneous transluminal angioplasty with a DCB, with a reduction in recurrent restenosis and target lesion revascularization (TLR) at least at 1 year after POBA. The consistent and positive results of different registries and randomized trials support the use of DCB to reduce SFA ISR recurrence.
Computational Protein Phenotype Characterization of IL10RA Mutations Causative to Early Onset Inflammatory Bowel Disease (IBD)

The deleterious amino acid substitution mutations in IL-10 receptor alpha gene are most frequently reported in several autoimmune diseases including early onset-inflammatory bowel disease (IBD). Despite the important role of IL-10 RA in maintaining immune homeostasis, the specific structural and functional implications of these mutations on protein phenotype, stability, ligand binding and post translational characteristics is not well explored. Therefore, this study performed the multidimensional computational analysis of IL10RA missense variations causative to pediatric or early onset inflammatory bowel disease (<5 years of age). Our computational algorithmic screening identified the deleterious nature of p. W45G, p. Y57C, p. W69G, p.T84I, p.Y91C, p.R101W, p.R117C, and p.R117H, IBD causative IL10-RA mutations. The sensitivity and specificity analysis of different computational methods showed that CADD outperform SIFT, PolyPhen 2.0, FATHMM, LRT, MetaLR, MetaSVM, PROVEAN and Condel in predicting the pathogenicity of IL10RA mutations. Our three-dimensional protein modeling assays showed that the point mutations cause major drifts in the structural plasticity of IL10 RA molecule and negatively influence its stability. Findings from molecular docking analysis have shown that these point mutations decrease the binding affinity of IL10RA toward IL10 and may likely to disturb the IL10 signaling pathway. This study provides an easy frame work for phenotypic characterization of mutant IL10RA molecule in terms of structure, flexibility and stability aspects. Our approach may also add a new dimension to conventional functional biology assays in quickly studying IL10 RA mutations and also for designing and developing inhibitors for mutant IL10RA molecule.
Research priorities in suicide prevention: A qualitative study of stakeholders’ views

Abstract The current study sought to inform priority setting in Australian suicide prevention research, by seeking stakeholders’ views on where future priorities might lie. Three group interviews were conducted with a total of 28 participants. Group interview participants stressed that priority should be given to evaluating the efficacy of specific interventions and examining the response of the health and community service systems. They felt that the epidemiological profile of suicidal individuals had been explored, at least with respect to rates and individual-level risk factors, and that the above evaluative activities should focus on groups identified as having particularly high levels of risk. Most saw limited value in continuing to explore individual-level risk factors ad infinitum, and felt that the time had come to move on to considering wider societal influences on suicide and individual-level protective factors. Many felt that evaluation efforts should employ mixed methods, should be multidisciplinary and should be relevant to the Australian context. They also argued that there was scope for increasing the utility of research findings by communicating them in a manner that would enable them to be utilised by policy-makers, planners and practitioners. Several called for a more cohesive framework for suicide prevention that could guide suicide prevention research. The current study provides some guidance with respect to the direction Australia’s suicide prevention research agenda should take. A priority-driven approach to suicide prevention research will ensure that the research endeavour provides the most useful information for those whose day-to-day work involves trying to prevent suicide.
Toll Like Receptor 2 signaling as a target for Ara-LAM mediated protection in Man LAM induced pathogenesis

Mannosylated Lipoarabinomannan (Man-LAM) produced by virulent Mycobacteria favors mycobacterial pathogenesis by the suppression of pro-inflammatory microenvironment within the host cell, but Arabinosylated Lipoarabinomannan (Ara-LAM) from avirulent mycobacteria evokes pro-inflammatory responses via induction of Toll like receptor-2 (TLR-2) mediated signaling. In this study, we investigated whether Ara-LAM could induce the TLR-2 signaling and pro-inflammatory cytokine gene transcription during Man-LAM induced pathogenesis in murine macrophages. Ara-LAM pre-treatment (3  g/ml) of Man-LAM treated macrophages induced association of TLR-2 with its downstream factor MyD88 and subsequently of MyD88 and IRAKs, leading to Ikk phosphorylation, IkB-  degradation, finally translocation and DNA binding of NF-B. These events culminated in the up-regulation of cytokines TNF-  and IL-12, nitrite generation and iNOS mRNA expression, which could be abrogated significantly by treatment of macrophages with TLR-2 specific siRNA as well as anti-TLR-2 monoclonal antibody. Based on our observations, we strongly report the TLR-2 mediated protection of Ara-LAM during Man-LAM-mediated pathogenesis.
Automatic detection of apical roots in oral radiographs

The apical root regions play an important role in analysis and diagnosis of many oral diseases. Automatic detection of such regions is consequently the first step toward computer-aided diagnosis of these diseases. In this paper we propose an automatic method for periapical root region detection by using the state-of-theart machine learning approaches. Specifically, we have adapted the AdaBoost classifier for apical root detection. One challenge in the task is the lack of training cases especially for diseased ones. To handle this problem, we boost the training set by including more root regions that are close to the annotated ones and decompose the original images to randomly generate negative samples. Based on these training samples, the Adaboost algorithm in combination with Haar wavelets is utilized in this task to train an apical root detector. The learned detector usually generates a large amount of true and false positives. In order to reduce the number of false positives, a confidence score for each candidate detection result is calculated for further purification. We first merge the detected regions by combining tightly overlapped detected candidate regions and then we use the confidence scores from the Adaboost detector to eliminate the false positives. The proposed method is evaluated on a dataset containing 39 annotated digitized oral X-Ray images from 21 patients. The experimental results show that our approach can achieve promising detection accuracy.
Optimal control of weighted networks based on node connection strength

Exploring how connection strengths between nodes affect the cost in controlling complex networks with fixed topological structure is an important issue both in theory and applications. In this paper, by considering optimal control of the networks, a matrix function optimization model is proposed to address such an issue. With pre-given input matrix, a normalized gradient descent method (NPGM) is developed to solve the optimization problem, so as to obtain the optimal connection strength matrix. With proposed NPGM, we find that a network adaptively changes its connection strength such that several control-flow subnetworks are self-formed. Moreover, we further point out that the control cost with optimal weight matrix is smallest when pre-located controller sources distribute evenly. These findings provide a comprehensive understanding of the impact of connection link weight on control cost for complex networks.
The democratization of deep learning in TASS 2017

This research work is partially supported by REDES project (TIN2015-65136-C2-1-R) and SMART project (TIN2017-89517-P) from the Spanish Government, and a grant from the Fondo Europeo de Desarrollo Regional (FEDER). Eugenio Martinez Camara was supported by the Juan de la Cierva Formacion Programme (FJCI-2016-28353) from the Spanish Government.