Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative facile methods for preparing graphene oxide–hydroxyapatite for bone tissue engineering

Motivated by the success of using graphene oxide (GO) as a nanofiller of composites, there is a drive to search for this new kind of carbon material as a bioactive component in ceramic materials. In the present study, biomineralized GO was prepared by two different approaches, represented by in situ sol–gel synthesis and biomimetic treatment. It was found that in the biocomposites obtained by the sol–gel approach, the spindle‐like hydroxyapatite nanoparticles, with a diameter of ca. 5 ± 0.37 nm and a length of ca. 70 ± 2.5 nm, were presented randomly and strongly on the surface. The oxygen‐containing functional groups, such as hydroxyl and carbonyl, present on the basal plane and edges of the GO sheets, play an important role in anchoring calcium ions, as demonstrated by FT–IR and TEM investigations. A different result was obtained for biocomposites after biomimetic treatment: an amorphous calcium phosphate on GO sheet was observed after 5 days of treatment. These different approaches resulted in a diverse effect on the proliferation and differentiation of osteogenic mesenchymal stem cells. In fact, in biocomposites prepared by the sol–gel approach the expression of an early marker of osteogenic differentiation, ALP, increases with the amount of GO in the first days of cell culture. Meanwhile, biomimetic materials sustain cell viability and proliferation, even if the expression of alkaline phosphatase activity in a basal medium is delayed. These findings may provide new prospects for utilizing GO‐based hydroxyapatite biocomposites in bone repair, bone augmentation and coating of biomedical implants and broaden the application of GO sheets in biological areas. Copyright © 2016 John Wiley & Sons, Ltd.
Both Regulatory T Cells and Antitumor Effector T Cells Are Primed in the Same Draining Lymph Nodes during Tumor Progression1

The peripheral tolerance mechanism prevents effective antitumor immunity, even though tumor cells possess recognizable tumor-associated Ags. Recently, it has been elucidated that regulatory T cells (Treg) play a critical role in maintaining not only self-tolerance, but also tolerance of tumor cells. However, because the Treg that maintain self-tolerance arise naturally in the thymus and are thought to be anergic in peripheral, it is still unclear where and when Treg for tumor cells are generated. In this study we analyze tumor-draining lymph nodes (LNs) and demonstrate that both antitumor effector T cells and Treg capable of abrogating the antitumor reactivity of the effector T cells are primed in the same LNs during tumor progression. The regulatory activity generated in tumor-draining LNs exclusively belonged to the CD4+ T cell subpopulation that expresses both CD25 and a high level of CD62L. Forkhead/winged helix transcription factor gene expression was detected only in the CD62LhighCD4+CD25+ T cells. CD62LhighCD4+CD25+ Treg and CD62LlowCD4+CD25+ T cells, which possess effector T cell functions, had comparable expression of LFA-1, VLA-4, CTLA-4, lymphocyte activation gene-3, and glucocorticoid-induced TNFR. Thus, only CD62L expression could distinguish regulatory CD4+CD25+ cells from effector CD4+CD25+ cells in draining LNs as a surface marker. The Treg generated in tumor-draining LNs possess the same functional properties as the Treg that arise naturally in the thymus but recognize tumor-associated Ag. CD62LhighCD4+CD25+ Treg contained a subpopulation that expressed CD86. Blocking experiments revealed that ligation of CTLA-4 on effector T cells by CD86 on Treg plays a pivotal role in regulating CD4+ effector T cells.
Inattentional blindness: the role of perceptual load, effects of stimulus type and position, and development over childhood.

Inattentional blindness refers to a failure to detect visible objects when attention is engaged in a task. Despite the central role for attention implied by its name, there is surprisingly little evidence that inattentional blindness indeed results from inattention. In this thesis I provide such evidence in demonstrating that rates of inattentional blindness critically depend on the extent to which a relevant task exhausts attentional capacity (under high perceptual load) or leaves spare capacity (under low perceptual load) for determining awareness of task-irrelevant stimuli. This was found when load was increased by requiring a more subtle line-length judgment in the traditional inattentional blindness cross-task, or by increasing the number of items in a visual search task. Further experiments generalised the effects of perceptual load on awareness across simple shapes and meaningful objects, and for irrelevant stimuli appearing in the periphery and at fixation. By contrast, upright (but not inverted) faces reached awareness regardless of the level of perceptual load in the relevant task. These findings are consistent with previous behavioural perceptual load studies using reaction time (RT) measures of task-irrelevant processing (Lavie, 1995 Lavie, Ro & Russell, 2003 see Lavie, 2005 for review) and support the conclusion that perceptual load determines conscious awareness. The experiments also found no advantage for awareness at fixation versus awareness at the periphery, highlighting a potential dissociation between awareness measures and distracter effects on RTs (which have previously shown such an advantage, Beck & Lavie, 2005). Finally, this thesis presents a preliminary investigation of the development of awareness as measured by rates of inattentional blindness under different levels of task load in children and in adults. Results demonstrated a clear pattern of increasing awareness with increasing age, and lend partial support to the notion that the development of attentional capacity underlies this trend in awareness.
Kaposi's Sarcoma-Associated Herpesvirus Reactivation Is Regulated by Interaction of Latency-Associated Nuclear Antigen with Recombination Signal Sequence-Binding Protein Jκ, the Major Downstream Effector of the Notch Signaling Pathway

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is the major biological cofactor contributing to development of Kaposi's sarcoma. KSHV establishes a latent infection in human B cells expressing the latency-associated nuclear antigen (LANA), a critical factor in the regulation of viral latency. LANA controls KSHV latent infection through repression of RTA, an activator of many lytic promoters. RTA activates the expression of several lytic viral genes by interacting with recombination signal sequence-binding protein Jκ (RBP-Jκ), a transcriptional repressor and the target of the Notch signaling pathway. The recognition that a number of KSHV lytic gene promoters, including RTA, contain RBP-Jκ binding sites raised the possibility that RBP-Jκ-mediated repression may be central to the establishment of latency. Here, we tested this hypothesis by examining the regulation of RTA by LANA through binding to RBP-Jκ. This study demonstrates that LANA physically associates with RBP-Jκ in vitro and in KSHV-infected cells, with the complex formed capable of binding to RBP-Jκ cognate sequences. RBP-Jκ binding sites within the RTA promoter have been found to be critical for LANA-mediated repression. Our study describes a novel mechanism through which LANA maintains KSHV latency by targeting a major downstream effector of the Notch signaling pathway.
Attenuation of Phosphorylation-dependent Activation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Disease-causing Mutations at the Transmission Interface*

Cystic fibrosis transmembrane conductance regulator (CFTR) is a multidomain membrane protein that functions as a phosphorylation-regulated anion channel. The interface between its two cytosolic nucleotide binding domains and coupling helices conferred by intracellular loops extending from the channel pore domains has been referred to as a transmission interface and is thought to be critical for the regulated channel activity of CFTR. Phosphorylation of the regulatory domain of CFTR by protein kinase A (PKA) is required for its channel activity. However, it was unclear if phosphorylation modifies the transmission interface. Here, we studied purified full-length CFTR protein using spectroscopic techniques to determine the consequences of PKA-mediated phosphorylation. Synchrotron radiation circular dichroism spectroscopy confirmed that purified full-length wild-type CFTR is folded and structurally responsive to phosphorylation. Intrinsic tryptophan fluorescence studies of CFTR showed that phosphorylation reduced iodide-mediated quenching, consistent with an effect of phosphorylation in burying tryptophans at the transmission interface. Importantly, the rate of phosphorylation-dependent channel activation was compromised by the introduction of disease-causing mutations in either of the two coupling helices predicted to interact with nucleotide binding domain 1 at the interface. Together, these results suggest that phosphorylation modifies the interface between the catalytic and pore domains of CFTR and that this modification facilitates CFTR channel activation.
Prophylactic administration of haloperidol plus midazolam reduces postoperative nausea and vomiting better than using each drug alone in patients undergoing middle ear surgery

Aims: The efficacy of using midazolam or haloperidol for prevention of postoperative nausea and vomiting (PONV) has been investigated before. The main object of the present study was to evaluate the anti-emetic effects of combining administration of intravenous haloperidol with intravenous midazolam on PONV in patients underwent middle ear surgery in comparison with using each drug alone. Methods: Study design was randomized, double-blind, placebo-controlled. 80 patients, aged 18-60 years, scheduled for middle ear surgery in Kashani Hospital Medical Center under general anesthesia were enrolled in this randomized, double-blind, placebo-controlled study. Patients were divided into 4 groups of 20 each and received haloperidol 2 mg i.v. (Group H); midazolam 2 mg i.v. (Group M); haloperidol 2 mg plus midazolam 2 mg i.v. (Group HM); saline i.v. (Group C). The incidences of PONV and complete response were evaluated at 0-2 hours after arrival to the PACU and 2-24 hours after arrival to the ward in 4 groups. Results: Patients in group HM had significantly lower incidence of PONV compared with groups H, M, and C throughout 0-24 h (P<00.5). The HM group had the lowest incidence of PONV (0-2, 2-24, and 0-24 h) and the highest incidence of complete response. Postoperative anti-emetic requirement was significantly less in group HM compared with group M or H (P<0.05). Conclusion: Combine administration of haloperidol 2 mg plus midazolam 2 mg significantly reduced PONV better than using each drug alone in patients underwent middle ear surgery under general anesthesia.
Therapeutic Efficacy in Experimental Polyarthritis of Viral-Driven Enkephalin Overproduction in Sensory Neurons

Rheumatoid arthritis is characterized by erosive inflammation of the joints, new bone proliferation, and ankylosis, leading to severely reduced locomotion and intense chronic pain. In a model of this disease, adjuvant-induced polyarthritis in the rat, neurons involved in pain transmission and control undergo plastic changes, especially at the spinal level. These changes affect notably neurons that contain opioids, such as enkephalins deriving from preproenkephalin A (PA) precursor protein. Using recombinant herpes simplex virus containing rat PA cDNA, we enhanced enkephalin synthesis in sensory neurons of polyarthritic rats. This treatment markedly improved locomotion and reduced hyperalgesia. Furthermore, the progression of bone destruction slowed down, which is the most difficult target to reach in the treatment of patients suffering from arthritis. These data demonstrate the therapeutic efficacy of enkephalin overproduction in a model of systemic inflammatory and painful chronic disorder.
Incidence and natural history of hepatitis E virus coinfection among HIV-infected patients

Objectives:To know the prevalence, incidence and factors associated with hepatitis E virus (HEV) infection in HIV-infected individuals in Spain, as well as to provide information on the natural history of HIV/HEV coinfection. Design:Prospective cohort study. Methods:Serum HEV IgG antibodies were tested in 613 HIV-infected patients at baseline and 2 years thereafter. Positive samples were tested for HEV-RNA. In patients with seroconversion, changes in liver function tests, serum HEV IgM antibodies and HEV RNA in samples collected between the baseline and the final time points were analyzed. Results:One hundred and sixty-one (26%) patients tested positive for serum HEV IgG antibodies at baseline. HEV exposure was more common in men than in women (28 vs. 18%; P = 0.022) and increased linearly with age: 16, 26 and 44% in younger than 40, from 40 to 49 and older than 50 years, respectively (P = 0.000002). One patient bore the serum HEV-RNA at baseline. Eighteen (4%) HEV-seronegative patients seroconverted during the follow-up. None of the factors predicted seroconversion. One patient with seroconversion developed acute hepatitis and four mild hypertransaminasemia without another apparent cause. No case of seroconversion evolved to chronic HEV infection. Seroreversion was detected in 19% of the HEV-seropositive patients at baseline. Patients with seroreversion showed more commonly CD4+ cell counts below 500 cells/&mgr;l than those who remained seropositive (77 vs. 46%; P = 0.004). Conclusions:Exposure to HEV among HIV-infected patients in Spain is very common, and this increases with age. Evolution to chronic infection is extremely unusual. Most cases of acute HEV infection seem to be clinically and biochemically unexpressive, therefore going unnoticed.
Distributed Algorithms for Consensus and Coordination in the Presence of Packet-Dropping Communication Links - Part II: Coefficients of Ergodicity Analysis Approach

In this two-part paper, we consider multicomponent systems in which each component can iteratively exchange information with other components in its neighborhood in order to compute, in a distributed fashion, the average of the components' initial values or some other quantity of interest (i.e., some function of these initial values). In particular, we study an iterative algorithm for computing the average of the initial values of the nodes. In this algorithm, each component maintains two sets of variables that are updated via two identical linear iterations. The average of the initial values of the nodes can be asymptotically computed by each node as the ratio of two of the variables it maintains. In the first part of this paper, we show how the update rules for the two sets of variables can be enhanced so that the algorithm becomes tolerant to communication links that may drop packets, independently among them and independently between different transmission times. In this second part, by rewriting the collective dynamics of both iterations, we show that the resulting system is mathematically equivalent to a finite inhomogenous Markov chain whose transition matrix takes one of finitely many values at each step. Then, by using e a coefficients of ergodicity approach, a method commonly used for convergence analysis of Markov chains, we prove convergence of the robustified consensus scheme. The analysis suggests that similar convergence should hold under more general conditions as well.
Epithelial-mesenchymal transition mediates anoikis resistance and enhances invasion in pleural effusion-derived human lung cancer cells

Epithelial-mesenchymal transition (EMT) is implicated in cancer pathological processes, particularly cancer invasion and metastasis. The present study demonstrated that EMT was critical for the metastasic potential of lung cancer cells isolated from a patient. P1 primary lung cancer cells were found to exhibit increased anoikis resistance compared with established A549, H23 and H460 lung cancer cells. Results of migration and invasion assays revealed that the invasion capability of P1 and A549 cells was higher than that of H23 and H460 cells. However, the migration of P1 cells was similar to that of H23 and H460 cells while A549 demonstrated a superior migrating ability. Western blot analysis indicated that while E-cadherin levels in all lung cancer cells were identified as comparable, P1 cells expressed the highest levels of N-cadherin. In the present study, detachment of cells was demonstrated for the first time to stimulate further transition of E-cadherin to N-cadherin. In addition, this obervation was more pronounced in P1 cells. These observations highlight the importance of EMT in cancer metastasis. In order to study the effect of ethnicity on cancer cell behavior, in the future a large number of Thai patient-derived cell lines must be analyzed.
Mapping‐by‐sequencing in complex polyploid genomes using genic sequence capture: a case study to map yellow rust resistance in hexaploid wheat

Summary Previously we extended the utility of mapping‐by‐sequencing by combining it with sequence capture and mapping sequence data to pseudo‐chromosomes that were organized using wheat–Brachypodium synteny. This, with a bespoke haplotyping algorithm, enabled us to map the flowering time locus in the diploid wheat Triticum monococcum L. identifying a set of deleted genes (Gardiner et al., 2014). Here, we develop this combination of gene enrichment and sliding window mapping‐by‐synteny analysis to map the Yr6 locus for yellow stripe rust resistance in hexaploid wheat. A 110 MB NimbleGen capture probe set was used to enrich and sequence a doubled haploid mapping population of hexaploid wheat derived from an Avalon and Cadenza cross. The Yr6 locus was identified by mapping to the POPSEQ chromosomal pseudomolecules using a bespoke pipeline and algorithm (Chapman et al., 2015). Furthermore the same locus was identified using newly developed pseudo‐chromosome sequences as a mapping reference that are based on the genic sequence used for sequence enrichment. The pseudo‐chromosomes allow us to demonstrate the application of mapping‐by‐sequencing to even poorly defined polyploidy genomes where chromosomes are incomplete and sub‐genome assemblies are collapsed. This analysis uniquely enabled us to: compare wheat genome annotations; identify the Yr6 locus – defining a smaller genic region than was previously possible; associate the interval with one wheat sub‐genome and increase the density of SNP markers associated. Finally, we built the pipeline in iPlant, making it a user‐friendly community resource for phenotype mapping.
ES is more than just a traditional finite-difference approximator

An evolution strategy (ES) variant based on a simplification of a natural evolution strategy recently attracted attention because it performs surprisingly well in challenging deep reinforcement learning domains. It searches for neural network parameters by generating perturbations to the current set of parameters, checking their performance, and moving in the aggregate direction of higher reward. Because it resembles a traditional finite-difference approximation of the reward gradient, it can naturally be confused with one. However, this ES optimizes for a different gradient than just reward: It optimizes for the average reward of the entire population, thereby seeking parameters that are robust to perturbation. This difference can channel ES into distinct areas of the search space relative to gradient descent, and also consequently to networks with distinct properties. This unique robustness-seeking property, and its consequences for optimization, are demonstrated in several domains. They include humanoid locomotion, where networks from policy gradient-based reinforcement learning are significantly less robust to parameter perturbation than ES-based policies solving the same task. While the implications of such robustness and robustness-seeking remain open to further study this work's main contribution is to highlight such differences and their potential importance.
Uptake of N,N′-Diacetylchitobiose [(GlcNAc)2] via the Phosphotransferase System Is Essential for Chitinase Production by Serratia marcescens 2170

ABSTRACT The chiR gene of Serratia marcescens 2170, encoding a LysR-type transcriptional activator, was identified previously as an essential factor for expression of chitinases and a chitin-binding protein, CBP21. To identify other genes that are essential for chitinase production, transposon mutagenesis with mini-Tn5Km1 was carried out, and 25 mutants that were unable to produce chitinases and CBP21 were obtained. Analysis of the mutated gene of one of the mutants, N22, revealed the presence of a pts operon in this bacterium, and a mutation was found in ptsI in the operon. In addition to its inability to produce chitinase, N22 did not grow well on N-acetyl-d-glucosamine (GlcNAc), (GlcNAc)2, and some other carbon sources, most of which were phosphotransferase system (PTS) sugars. Thus, the inability to produce chitinase was assumed to be caused by the defect in uptake of (GlcNAc)2 via the PTS, considering that (GlcNAc)2 is the minimal substrate for chitinase induction and the major product of chitin hydrolysis by chitinases of this bacterium. To confirm this assumption, the chb operon, encoding the (GlcNAc)2-specific enzyme II permease, was cloned by reference to its Escherichia coli counterpart, and the Serratia chb operon was shown to comprise chbB, chbC, bglA, chbR, and chbG. Disruption of chbC drastically reduced production of chitinases and CBP21 and impaired growth on colloidal chitin. These results indicate that uptake of (GlcNAc)2 is mediated by the PTS and that the (GlcNAc)2-specific enzyme II permease constitutes its major pathway. Since (GlcNAc)2 uptake is essential for induction of chitinases and CBP21 production, (GlcNAc)2 appears to be the key molecule in recognition and utilization of chitin by S. marcescens.