Miracle-dz/UniFAR-FTUs huggingface dataset:
Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis

Objective To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). Method We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon–intron boundaries, and 5 kb flanking DNA in the 5′ and 3′ UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into ‘mild’ and ‘severe’ groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. Results Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10−5), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10−3). There was no observed association between radiographic severity and HLA-B*27. Conclusions These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.
Two‐weekly dose‐adjusted (DA)‐EPOCH‐like chemotherapy with high‐dose dexamethasone plus rituximab (DA‐EDOCH14‐R) in poor‐prognostic untreated diffuse large B‐cell lymphoma

The activity and safety of two‐weekly dose‐adjusted (DA)‐EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)‐like chemotherapy with high‐dose dexamethasone plus rituximab (DA‐EDOCH14‐R) was explored in 20 patients with previously untreated poor prognosis diffuse large B‐cell lymphoma (DLBCL). The main outcomes were compared with those of 27 poor‐prognosis patients enrolled into a previous trial of 3‐weekly DA‐EPOCH‐R. Toxicity was manageable and there were no therapy‐related deaths. Three‐year progression‐free survival (PFS) was superior in the DA‐EDOCH14‐R group (95% vs. 74%, P = 0·08). Importantly, this improvement in PFS with the two‐weekly DA‐EDOCH14‐R was particularly notable in patients with an age‐adjusted International Prognostic Index of 3 (100% vs. 30%, P < 0·001).
Accuracy evaluations of axial localisation algorithms in confocal microscopy

The localisation accuracy of axial peaks is an important factor for height determination in a confocal microscope. Several algorithms have been proposed for height extraction in surface topography measurements. However, some algorithms ignore the influence of error and discrete sampling on the accuracy. This paper analyzes the localisation accuracy of some common algorithms under different aberrations and random errors, and discusses the effect of axial scanning interval on the accuracy of each algorithm. Finally, we get the application scope of each algorithm. Our results offer a reference for selecting algorithms for confocal metrology.
High glucose‐induced oxidative stress and mitochondrial dysfunction in neurons

The current study examines the association between glucose induction of reactive oxygen species (ROS), mitochondrial (Mt) depolarization, and programmed cell death in primary neurons. In primary dorsal root ganglion (DRG) neurons, 45 mM glucose rapidly induces a peak rise in ROS Corresponding to a 50% increase in mean Mt size at 6 h (P<0.001). This is coupled with loss of regulation of the Mt membrane potential (Mt membrane hyperpolarization, followed by depolarization, MMD), partial depletion of ATP, and activation of caspase‐3 and ‐9. Glucose‐induced activation of ROS, MMD, and caspase‐3 and ‐9 activation is inhibited by myxothiazole and thenoyltrifluoroacetone (P<0.001), which inhibit specific components of the Mt electron transfer chain. Similarly, MMD and caspase‐3 activation are inhibited by 100 fM bongkrekic acid (an inhibitor of the adenosine nucleotide translocase ANT). These results indicate that mild increases in glucose induce ROS and Mt swelling that precedes neuronal apoptosis. Glucotoxicity is blocked by inhibiting ROS induction, MMD, or caspase cleavage by specific inhibitors of electron transfer, or by stabilizing the ANT. —Russell, J. W. , Golovoy, D. , Vincent, A. M. , Mahendru, P., Olzmann, J. A. , Mentzer, A. , Feldman, E. L. High glucose‐induced oxidative stress and mitochondrial dysfunction in neurons. FASEB J. 16, 1738–1748 (2002)
MESSENGER Observations of Mercury’s Exosphere: Detection of Magnesium and Distribution of Constituents

MESSENGER from Mercury The spacecraft MESSENGER passed by Mercury in October 2008, in what was the second of three fly-bys before it settles into the planet's orbit in 2011. Another spacecraft visited Mercury in the mid-1970s, which mapped 45% of the planet's surface. Now, after MESSENGER, only 10% of Mercury's surface remains to be imaged up close. Denevi et al. (p. 613) use this near-global data to look at the mechanisms that shaped Mercury's crust, which likely formed by eruption of magmas of different compositions over a long period of time. Like the Moon, Mercury's surface is dotted with impact craters. Watters et al. (p. 618) describe a well-preserved impact basin, Rembrandt, which is second in size to the largest known basin, Caloris. Unlike Caloris, Rembrandt is not completely filled by material of volcanic origin, preserving clues to its formation and evolution. It displays unique patterns of tectonic deformation, some of which result from Mercury's contraction as its interior cooled over time. Mercury's exosphere and magnetosphere were also observed (see the Perspective by Glassmeier). Magnetic reconnection is a process whereby the interplanetary magnetic field lines join the magnetospheric field lines and transfer energy from the solar wind into the magnetosphere. Slavin et al. (p. 606) report observations of intense magnetic reconnection 10 times as intense as that of Earth. McClintock et al. (p. 610) describe simultaneous, high-resolution measurements of Mg, Ca, and Na in Mercury's exosphere, which may shed light on the processes that create and maintain the exosphere. High-resolution observations of Mercury’s exosphere reveal different spatial distributions of magnesium, calcium, and sodium. Mercury is surrounded by a tenuous exosphere that is supplied primarily by the planet’s surface materials and is known to contain sodium, potassium, and calcium. Observations by the Mercury Atmospheric and Surface Composition Spectrometer during MESSENGER’s second Mercury flyby revealed the presence of neutral magnesium in the tail (anti-sunward) region of the exosphere, as well as differing spatial distributions of magnesium, calcium, and sodium atoms in both the tail and the nightside, near-planet exosphere. Analysis of these observations, supplemented by observations during the first Mercury flyby, as well as those by other MESSENGER instruments, suggests that the distinct spatial distributions arise from a combination of differences in source, transfer, and loss processes.
Sevoflurane Alters Spatiotemporal Functional Connectivity Motifs That Link Resting-State Networks during Wakefulness

Background: The spatiotemporal patterns of correlated neural activity during the transition from wakefulness to general anesthesia have not been fully characterized. Correlation analysis of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) allows segmentation of the brain into resting-state networks (RSNs), with functional connectivity referring to the covarying activity that suggests shared functional specialization. We quantified the persistence of these correlations following the induction of general anesthesia in healthy volunteers and assessed for a dynamic nature over time. Methods: We analyzed human fMRI data acquired at 0 and 1.2% vol sevoflurane. The covariance in the correlated activity among different brain regions was calculated over time using bounded Kalman filtering. These time series were then clustered into eight orthogonal motifs using a K-means algorithm, where the structure of correlated activity throughout the brain at any time is the weighted sum of all motifs. Results: Across time scales and under anesthesia, the reorganization of interactions between RSNs is related to the strength of dynamic connections between member pairs. The covariance of correlated activity between RSNs persists compared to that linking individual member pairs of different RSNs. Conclusions: Accounting for the spatiotemporal structure of correlated BOLD signals, anesthetic-induced loss of consciousness is mainly associated with the disruption of motifs with intermediate strength within and between members of different RSNs. In contrast, motifs with higher strength of connections, predominantly with regions-pairs from within-RSN interactions, are conserved among states of wakefulness and sevoflurane general anesthesia.
Targeting of Interferon-Beta to Produce a Specific, Multi-Mechanistic Oncolytic Vaccinia Virus

Background Oncolytic viruses hold much promise for clinical treatment of many cancers, but a lack of systemic delivery and insufficient tumor cell killing have limited their usefulness. We have previously demonstrated that vaccinia virus strains are capable of systemic delivery to tumors in mouse models, but infection of normal tissues remains an issue. We hypothesized that interferon-beta (IFN-β) expression from an oncolytic vaccinia strain incapable of responding to this cytokine would have dual benefits as a cancer therapeutic: increased anticancer effects and enhanced virus inactivation in normal tissues. We report the construction and preclinical testing of this virus. Methods and Findings In vitro screening of viral strains by cytotoxicity and replication assay was coupled to cellular characterization by phospho-flow cytometry in order to select a novel oncolytic vaccinia virus. This virus was then examined in vivo in mouse models by non-invasive imaging techniques. A vaccinia B18R deletion mutant was selected as the backbone for IFN-β expression, because the B18R gene product neutralizes secreted type-I IFNs. The oncolytic B18R deletion mutant demonstrated IFN-dependent cancer selectivity and efficacy in vitro, and tumor targeting and efficacy in mouse models in vivo. Both tumor cells and tumor-associated vascular endothelial cells were targeted. Complete tumor responses in preclinical models were accompanied by immune-mediated protection against tumor rechallenge. Cancer selectivity was also demonstrated in primary human tumor explant tissues and adjacent normal tissues. The IFN-β gene was then cloned into the thymidine kinase (TK) region of this virus to create JX-795 (TK−/B18R−/IFN-β+). JX-795 had superior tumor selectivity and systemic intravenous efficacy when compared with the TK−/B18R− control or wild-type vaccinia in preclinical models. Conclusions By combining IFN-dependent cancer selectivity with IFN-β expression to optimize both anticancer effects and normal tissue antiviral effects, we were able to achieve, to our knowledge for the first time, tumor-specific replication, IFN-β gene expression, and efficacy following systemic delivery in preclinical models.
Utilizing Dependency Language Models for Graph-based Dependency Parsing Models

Most previous graph-based parsing models increase decoding complexity when they use high-order features due to exact-inference decoding. In this paper, we present an approach to enriching high-order feature representations for graph-based dependency parsing models using a dependency languagemodel and beam search. The dependency language model is built on a large-amount of additional auto-parsed data that is processed by a baseline parser. Based on the dependency language model, we represent a set of features for the parsing model. Finally, the features are efficiently integrated into the parsing model during decoding using beam search. Our approach has two advantages. Firstly we utilize rich high-order features defined over a view of large scope and additional large raw corpus. Secondly our approach does not increase the decoding complexity. We evaluate the proposed approach on English and Chinese data. The experimental results show that our new parser achieves the best accuracy on the Chinese data and comparable accuracy with the best known systems on the English data.
Renin–Angiotensin–Aldosterone System Is Not Involved in the Arterial Stiffening Induced by Acute and Prolonged Exposure to High Altitude

This randomized, double-blind, placebo-controlled study was designed to explore the effects of exposure to very high altitude hypoxia on vascular wall properties and to clarify the role of renin–angiotensin–aldosterone system inhibition on these vascular changes. Forty-seven healthy subjects were included in this study: 22 randomized to telmisartan (age, 40.3±10.8 years; 7 women) and 25 to placebo (age, 39.3±9.8 years; 7 women). Tests were performed at sea level, pre- and post-treatment, during acute exposure to 3400 and 5400-m altitude (Mt. Everest Base Camp), and after 2 weeks, at 5400 m. The effects of hypobaric hypoxia on mechanical properties of large arteries were assessed by applanation tonometry, measuring carotid–femoral pulse wave velocity, analyzing arterial pulse waveforms, and evaluating subendocardial oxygen supply/demand index. No differences in hemodynamic changes during acute and prolonged exposure to 5400-m altitude were found between telmisartan and placebo groups. Aortic pulse wave velocity significantly increased with altitude (P<0.001) from 7.41±1.25 m/s at sea level to 7.70±1.13 m/s at 3400 m and to 8.52±1.59 m/s at arrival at 5400 m (P<0.0001), remaining elevated during prolonged exposure to this altitude (8.41±1.12 m/s; P<0.0001). Subendocardial oxygen supply/demand index significantly decreased with acute exposure to 3400 m: from 1.72±0.30 m/s at sea level to 1.41±0.27 m/s at 3400 m (P<0.001), remaining significantly although slightly less reduced after reaching 5400 m (1.52±0.33) and after prolonged exposure to this altitude (1.53±0.25; P<0.001). In conclusion, the acute exposure to hypobaric hypoxia induces aortic stiffening and reduction in subendocardial oxygen supply/demand index. Renin–angiotensin–aldosterone system does not seem to play any significant role in these hemodynamic changes. Clinical Trial Registration— URL: https://www.clinicaltrialsregister. eu/. Unique identifier: 2008-000540-14.
Surface functionalization of polypropylene and polyethylene films with allylamine by γ radiation

Allylamine (AA)-functionalized surfaces for cell adhesion and tissue engineering generated by plasma reactions present several disadvantages, such as amine degradation after 1 week of storage in air and difficulty in achieving a highly specific surface functionalization. In this work, polypropylene (PP) and polyethylene (PE) films were functionalized with AA by γ irradiation to enhance adhesion and compatibility without changing intrinsic bulk properties, thus avoiding the disadvantages of plasma synthesis. Irradiation grafting was realized by a direct and pre-irradiation oxidation method. The effect of different parameters studied were characterized by Fourier transform infrared spectra, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy, and contact angle measurements.
Construction of N-M Interaction Diagram for Reinforced Concrete Columns Strengthened with Steel Jackets Using Plastic Stress Distribution Method

No attempts have been made in developing the N-M interaction diagram for reinforced concrete columns strengthened with steel jackets using the plastic stress distribution method. Therefore, this paper presents an analytical model to construct the N-M interaction diagram for reinforced concrete columns strengthened with steel jackets using the plastic stress distribution method after assuming the behavior of strengthened column to be like composite column and including the effects of confinement on concrete compressive strength. The proposed model was compared with experimental results. The comparisons showed that the model is conservative and it reveals the ultimate strength of the strengthened column. A parametric study has been also carried out to investigate the influence of various parameters on the N-M interaction diagram of the strengthened column. These parameters were: dimensions of steel angle, yield stress of the steel angles, concrete compressive strength and the size of the reinforcement bars used in RC columns. The results made clear the effects of these parameters on the N-M interaction diagram, and encouraged the use of the model in preliminary strengthening studies.
Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles in the brain. Amyloid-β peptides (Aβ) are considered to play a critical role in the onset and progression of AD. Apigenin (4',5,7-trihydroxyflavone) is a pharmacologically active agent. Even though some evidence suggests that it has potential neuroprotective effects, no preexisting study has reported any therapeutic effects of apigenin in AD models. In the present study, we examined the effects of apigenin on cognitive function in APP/PS1 double transgenic AD mice and explored its mechanism(s) of action. Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice. Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels. Moreover, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase. In addition, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex. In conclusion, apigenin may ameliorate AD-associated learning and memory impairment through relieving Aβ burden, suppressing amyloidogenic process, inhibiting oxidative stress, and restoring ERK/CREB/BDNF pathway. Therefore, apigenin appears to represent an alternative medication for the prevention and/or therapy of AD.
Atmospheric effects on laser eye safety and damage to instrumentation

Electro-optical sensors as well as unprotected human eyes are extremely sensitive to laser radiation and can be permanently damaged from direct or reflected beams. Laser detector/eye hazard depends on the interaction between the laser beam and the media in which it traverses. The environmental conditions including terrain features, atmospheric particulate and water content, and turbulence, may alter the laser’s effect on the detector/eye. It is possible to estimate the performance of an electro-optical system as long as the atmospheric propagation of the laser beam can be adequately modeled. More recent experiments and modeling of atmospheric optics phenomena such as inner scale effect, aperture averaging, atmospheric attenuation in NIR-SWIR, and Cn2 modeling justify an update of previous eye/detector safety modeling. In the present work, the influence of the atmospheric channel on laser safety for personnel and instrumentation is shown on the basis of theoretical and experimental data of laser irradiance statistics for different atmospheric conditions. A method for evaluating the probability of damage and hazard distances associated with the use of laser systems in a turbulent atmosphere operating in the visible and NIR-SWIR portions of the electromagnetic spectrum is presented. It can be used as a performance prediction model for directed energy engagement of ground-based or air-based systems.
The synthesis and characterization of platinum nanoparticles: a method of controlling the size and morphology

In this paper, Pt nanoparticles with good shapes of nanocubes and nano-octahedra and well-controlled sizes in the range 5–7 and 8–12 nm, respectively, have been successfully synthesized. The modified polyol method by adding silver nitrate and varying the molar ratio of the solutions of silver nitrate and H2PtCl6 has been used to produce Pt nanoparticles of the size and shape to be controlled. The size and morphology of Pt nanoparticles have been studied by transmission electron microscopy (TEM) and high resolution TEM (HRTEM). The results have shown that their very sharp and good shapes exist in the main forms of cubic, cuboctahedral, octahedral and tetrahedral shapes directly related to the crystal nucleation along various directions of the {100} cubic, {111} octahedral and {111} tetrahedral facets during synthesis. In particular, various irregular and new shapes of Pt nanoparticles have been found. Here, it is concluded that the role of silver ions has to be considered as an important factor for promoting and controlling the development of Pt nanoparticles of {100} cubic, {111} octahedral and {111} tetrahedral facets, and also directly orienting the growth and formation of Pt nanoparticles.
Impaired pulmonary defense against Pseudomonas aeruginosa in VEGF gene inactivated mouse lung

Repeated bacterial and viral infections are known to contribute to worsening lung function in several respiratory diseases, including asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). Previous studies have reported alveolar wall cell apoptosis and parenchymal damage in adult pulmonary VEGF gene ablated mice. We hypothesized that VEGF expressed by type II cells is also necessary to provide an effective host defense against bacteria in part by maintaining surfactant homeostasis. Therefore, Pseudomonas aeruginosa (PAO1) levels were evaluated in mice following lung‐targeted VEGF gene inactivation, and alterations in VEGF‐dependent type II cell function were evaluated by measuring surfactant homeostasis in mouse lungs and isolated type II cells. In VEGF‐deficient lungs increased PAO1 levels and pro‐inflammatory cytokines, TNFα and IL‐6, were detected 24 h after bacterial instillation compared to control lungs. In vivo lung‐targeted VEGF gene deletion (57% decrease in total pulmonary VEGF) did not alter alveolar surfactant or tissue disaturated phosphatidylcholine (DSPC) levels. However, sphingomyelin content, choline phosphate cytidylyltransferase (CCT) mRNA, and SP‐D expression were decreased. In isolated type II cells an 80% reduction of VEGF protein resulted in decreases in total phospholipids (PL), DSPC, DSPC synthesis, surfactant associated proteins (SP)‐B and ‐D, and the lipid transporters, ABCA1 and Rab3D. TPA‐induced DSPC secretion and apoptosis were elevated in VEGF‐deficient type II cells. These results suggest a potential protective role for type II cell‐expressed VEGF against bacterial initiated infection. J. Cell. Physiol. 228: 371–379, 2013. © 2012 Wiley Periodicals, Inc.