Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequence‐selective, pH‐dependent binding to DNA of benzophenanthridine alkaloids

The sequence selectivity associated with binding to DNA of three alkaloids belonging to the benzophenanthridine family has been analysed by DNase I footprinting, and the results were compared with those obtained from an analysis of the behaviour of the standard intercalator, ethidium bromide. Like the ethidium, the benzophenanthridine compunds appear to bind best to regions of mixed nucleotide sequence, especially those containing alternating purines and pyrimidines, although there are some notable differences in behaviour. There is also a marked lack of binding to sequences such as (AT)n, where n⩾3. The binding to DNA of the benzophenanthridines is specifically related to the hydrogen ion concentration of the medium, in that the DNase I footprints are considerably enhanced when the reaction is performed at a pH below 7.0. We discuss these results in terms of a greater preponderance of the intercalating species being present at lower pH.
Realizing Auditor Independence in China: Insights from the Local Context

This study contributes to context-based auditing research by providing insights into the realization of auditor independence in China’s politico-economic and cultural context. Given the increasing legitimizing power and wide diffusion of Western corporate governance and accountability, it is crucial to examine the practice of imported concepts in countries such as China, where the development of accounting profession has taken a different path and been shaped by contextual influences different from those of Anglo-American countries. Twenty-one semi-structured interviews were used to obtain insights into auditor independence. The findings suggest a discrepancy between the imported construct of auditor independence and China’s institutional context. China’s politico-economic and social contexts have narrowed construction of auditor independence to its economic dimension. Given the pervasiveness of guanxi, low legal risk, and intense competition in the audit services market, Chinese auditors are under pressure to lower audit fees, avoid issuing qualified opinions, and provide additional advice and assistance on financial reporting. We argue that when auditor independence, as developed in Western economies, is implemented in transitional economies, there is a need to take into account its ability to adapt. Keywords: Auditing, Auditor Independence, China, Local Context To cite this document: Huiying Wu and Sammy Xiaoyan Ying, "Realizing Auditor Independence in China: Insights from the Local Context", Contemporary Management Research, Vol.12, No.2, pp. 245-272, 2016. Permanent link to this document: http://dx.doi. org/10.7903/cmr.15201
Wafer-level-package for Bulk Acoustic Wave (BAW) filters

Silicon based Bulk-Acoustic-Wave (BAW) filters utilize mainstream wafer processing and can create significant customer benefit in terms of cost, performance and size. Similar to conventional SAW filters the package is a dominant cost contributor as long as ceramic cavity packages are used. For both SAW and BAW the active area may not be coated with any package material. We report on an innovative process which enables to manufacture BAW filters in cheap plastic SMD packages similar to packages in use for diodes and transistors. Our process is based photo-epoxy SU-8 which allows to build air-cavities above the active areas of a filter. The process is cheap as it is done on wafer level and fits well into a CMOS manufacturing environment.
Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial.

CONTEXT High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined. OBJECTIVE To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI. DESIGN, SETTING, AND PATIENTS Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010. INTERVENTIONS High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months. MAIN OUTCOME MEASURES The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days. RESULTS At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001). CONCLUSIONS Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00645918.
Clustering based online automatic objective reduction to aid many-objective optimization

Starting from scalability to visualization, several challenges come into play when multi-objective optimization algorithms are applied to many-objective optimization problems. These challenges can be tackled using objective reduction algorithms. This work proposes a correlation based objective reduction algorithm. The set of points representing the Pareto-Front are clustered based on correlation distance. The constituent objectives belonging to the most compact cluster are pruned except the centroid. The reduction and search proceed while alternating between full set and reduced set. Number of clusters is gradually increased in order to zoom in the correlation structure of the objectives and the algorithm stops when the number of clusters equals to the number of objectives. This objective reduction leads to automatic detection of number of objectives, faster convergence as one or more number of objectives can be eliminated in reduction stages and improved performance as both global exploration and local exploitation of the search space are considered. The proposed approach of objective reduction is coupled with a differential evolution based multi-objective optimization technique to develop a solution framework for many-objective optimization problems. The efficacy of the proposed approach is tested on several benchmark functions viz. DTLZ1, DTLZ2, DTLZ3 and DTLZ4 for 10 and 20 objectives. Convergence metric and hypervolume indicator are used for comparing the performance of the proposed solution framework with other popular multi-objective optimization algorithms.
Treatment with drugs able to reduce iodine efflux significantly increases the intracellular retention time in thyroid cancer cells stably transfected with sodium iodide symporter complementary deoxyribonucleic acid.

CONTEXT One of the major limits of gene therapy with sodium iodide symporter (NIS), which enables cells to be subjected to radioiodine therapy, is that NIS-transfected cells rapidly release the intracellular iodine. METHODS We transfected human anaplastic (FRO) and medullary (TT) thyroid cancer-derived cell lines that were unable to take up iodine with human NIS cDNA. The possibility of increasing the iodine retention time by treating the transfected clones with myricetin, lithium, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) was explored. RESULTS We obtained 19 FRO and 16 TT clones stably transfected with NIS. Twelve of 19 FRO and nine of 16 TT clones expressed the full-length NIS mRNA; 11 of 12 FRO and four of nine TT clones were able to take up radioiodine and correctly expressed NIS protein on the plasma membrane. Kinetic analysis of iodide uptake in the two clones (FRO-19 and TT-2) with the highest uptaking activity revealed that the plateau was reached after 30 min by FRO-19 and after 60 min by TT-2. The t(1/2) of the iodide efflux was 9 min in FRO-19 and 20 min in TT-2. The treatment of the two cell lines with four different drugs revealed that DIDS and 17-AAG, but not myricetin and lithium, significantly increased the intracellular iodide retention time in FRO-19, but not in TT-2. CONCLUSIONS We showed that 17-AAG and DIDS prolong the retention time of (131)I in NIS-transfected thyroid tumoral cells, thus reinforcing the hope of using this approach for future clinical application, especially in patients with thyroid carcinoma who are no longer responsive to conventional therapy.
Methamphetamine‐induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling

Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial‐specific fractalkine receptor (CX3CR1) as an important mediator of MPTP‐induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH‐induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild‐type controls. The effects of METH in CX3CR1 knockout mice were not gender‐dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP‐microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal‐resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.
Mirroring and the ontogeny of social cognition

Making sense of the actions and intentions of others is critical for human social functioning and for social-cognitive development. Despite a great deal of interest in the development of action understanding and the broad impact that it can have on the emergence of social abilities (e.g., Brune and Woodward 2007; Wellman et al. 2008; Yamaguchi et al. 2009; Paulus et al. 2014; Krogh-Jespersen et al. in press), relatively little is known about the neural underpinnings of this foundational social-cognitive skill. In this chapter, we review recent research that suggests that mirroring—the process of activating one’s own action control system while observing someone else acting—may be linked to the development of action understanding. The hypothesis that the brain’s action control system shapes the ability to process and respond appropriately to the actions of others was initially inspired by research in animal neuroscience. Rizzolatti and colleagues (1996) identified individual neurons (mirror neurons) in the monkey motor cortex that discharge not only during action production but also when the animal observes another agent produce the relevant action. This finding, combined with parallel discoveries in neuroimaging studies with human adults, has led to wide-ranging proposals about the role that the motor system may play in supporting social cognition and social behavior. Among these predictions is the idea that activating one’s own motor system during perception allows the observer to interpret the actions of others in meaningful ways. Drawing on these action control resources could have wideranging implications for early development, a time when both motor and social abilities undergo foundational organization (Ferrari et al. 2013; Woodward and Gerson 2014). In this chapter, we consider one of these potential implications by exploring the evidence that mirroring may facilitate a fundamental aspect of action understanding—interpreting others’ actions in terms of their goal structure—in the first years of life. For adults, the perception of others’ actions as goal-directed is robust and automatic (Spunt and Lieberman 2013). When others reach for objects, for example, adults rapidly decipher the meaning behind this action at several levels, from the most basic (e.g., reaching for a plate) to the increasing abstract (e.g., beginning to clear the table). In this chapter,
LMP1 of Epstein-Barr Virus Induces Proliferation of Primary Mouse Embryonic Fibroblasts and Cooperatively Transforms the Cells with a p16-Insensitive CDK4 Oncogene

ABSTRACT The latent membrane protein LMP1 of Epstein-Barr virus (EBV) is often present in EBV-associated malignancies including nasopharyngeal carcinoma and Hodgkin's lymphoma. Previous work demonstrates that the LMP1 gene of EBV is sufficient to transform certain established rodent fibroblast cell lines and to induce the tumorigenicity of some human epithelial cell lines. In addition, LMP1 plays pleiotropic roles in cell growth arrest, differentiation, and apoptosis, depending on the background of the target cells. To examine the roles of LMP1 in cell proliferation and growth regulation in primary culture cells, we constructed a recombinant retrovirus containing an LMP1 gene. With this retrovirus, LMP1 was shown to stimulate the proliferation of primary mouse embryonic fibroblasts (MEF cells). It has a mitogenic activity for MEF cells, as demonstrated by an immediate induction of cell doubling time. In addition, it significantly extends the passage number of MEF cells to more than 30 after retroviral infection, compared with less than 5 for uninfected MEF cells. Furthermore, LMP1 cooperates with a p16-insensitive CDK4 R24C oncogene in transforming MEF cells. Our results provide the first evidence of the abilities of the LMP1 gene, acting alone, to effectively induce the proliferation of primary MEF cells and of its cooperativity with another cellular oncogene in transforming primary cells.
TOWARD EARLY-WARNING DETECTION OF GRAVITATIONAL WAVES FROM COMPACT BINARY COALESCENCE

Rapid detection of compact binary coalescence (CBC) with a network of advanced gravitational-wave detectors will offer a unique opportunity for multi-messenger astronomy. Prompt detection alerts for the astronomical community might make it possible to observe the onset of electromagnetic emission from CBC. We demonstrate a computationally practical filtering strategy that could produce early-warning triggers before gravitational radiation from the final merger has arrived at the detectors.
Steady state migratory RelB+ langerin+ dermal dendritic cells mediate peripheral induction of antigen‐specific CD4+CD25+Foxp3+ regulatory T cells

Tolerance to self‐antigens expressed in peripheral organs is maintained by CD4+ CD25+ Foxp3+ Treg cells, which are generated as a result of thymic selection or peripheral induction. Here, we demonstrate that steady‐state migratory DCs from the skin mediated Treg conversion in draining lymph nodes of mice. These DCs displayed a partially mature MHC IIint CD86int CD40hi CCR7+ phenotype, used endogenous TGF‐β for conversion and showed nuclear RelB translocation. Deficiency of the alternative NF‐κB signaling pathway (RelB/p52) reduced steady‐state migration of DCs. These DCs transported and directly presented soluble OVA provided by s.c. implanted osmotic minipumps, as well as cell‐associated epidermal OVA in transgenic K5‐mOVA mice to CD4+ OVA‐specific TCR‐transgenic OT‐II T cells. The langerin+ dermal DC subset, but not epidermal Langerhans cells, mediated conversion of naive OT‐II×RAG‐1−/− T cells into proliferating CD4+ CD25+ Foxp3+ Tregs. Thus, our data suggest that steady‐state migratory RelB+ TGF‐β+ langerin+ dermal DCs mediate peripheral Treg conversion in response to epidermal antigen in skin‐draining lymph nodes.
Toxic effects of some alcohol and ethylene glycol derivatives on Cladosporium resinae

Eleven commercially available alcohol and ethylene glycol derivatives were tested for their toxicity toward a problem organism in jet fuel, Cladosporium resinae. In the presence of glucose, 20% (vol/vol) ethylene glycol monomethyl ether prevented spore germination and mycelial growth, and 10% (vol/vol) 2-ethoxybutanol, 10% 2-isopropoxyethanol, 10% 3-methoxybutanol, 5% 2-butyloxyethanol, 5% ethylene glycol dibutyl ether, and 5% diethylene glycol monobutyl ether were found to have similar effects. In a biphasic kerosene-water system, 3-methoxybutanol, 2-butyloxyethanol, and diethylene glycol monobutyl ether were again found to be more toxic than ethylene glycol monomethyl ether. Considerable potassium efflux, protein leakage, and inhibition of endogenous respiration were observed in the presence of the more toxic compounds. 2-Butyloxyethanol also caused loss of sterols from cells.
Michigan Infrared Combiner (MIRC): commissioning results at the CHARA Array

The Michigan Infrared Combiner (MIRC) has been designed for two primary goals: 1) imaging with all six CHARA telescopes simultaneously in the near-infrared, 2) direct detection of "hot Jupiter" exoplanets using precision closure phases. In September 2005, MIRC was commissioned on-sky at the CHARA Array on Mt. Wilson, CA, successfully combining light from 4 telescopes simultaneously. After a brief overview of MIRC features and design philosophy, we provide detailed description of key components and present results of laboratory tests. Lastly, we present first results from the commissioning run, focusing on engineering performance. We also present remarkable on-sky closure phase results from the first night of recorded data with the best-ever demonstrated closure phase stability and precision (ΔΦ = 0.03 degrees).
The Sticking Heartbeat Aperture Resynchronization Protocol

As wireless sensor networks become more ubiquitous in the world, the need for lightweight, resilient time synchronization protocols is apparent. Wireless nodes' internal clocks are subject to drift over time due to manufacturing imperfections and environmental changes. While various protocols have been introduced that attempt to correct for this drift, they each have their own peculiarities and issues. This paper presents a new protocol, the Sticking Heartbeat Aperture Resynchronization Protocol (SHARP), that reduces synchronization error and resolves shortcomings of existing protocols. We have implemented and compared SHARP to two existing (and noteworthy) time synchronization protocols, Reference Broadcast Synchronization (RBS) and Simple Synchronization Protocol (SISP), on Atmel ATMega328p based microcontroller platforms with IEEE 802.15. 4 Xbee radio modules. We show that SHARP exhibits a higher level of synchronization than SISP (which in turn exhibited much better performance than RBS), while requiring significantly fewer messages.
Expression and Function of the Cholinergic System in Immune Cells

T and B cells express most cholinergic system components—e.g., acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase, and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Using ChATBAC-eGFP transgenic mice, ChAT expression has been confirmed in T and B cells, dendritic cells, and macrophages. Moreover, T cell activation via T-cell receptor/CD3-mediated pathways upregulates ChAT mRNA expression and ACh synthesis, suggesting that this lymphocytic cholinergic system contributes to the regulation of immune function. Immune cells express all five mAChRs (M1–M5). Combined M1/M5 mAChR-deficient (M1/M5-KO) mice produce less antigen-specific antibody than wild-type (WT) mice. Furthermore, spleen cells in M1/M5-KO mice produce less tumor necrosis factor (TNF)-α and interleukin (IL)-6, suggesting M1/M5 mAChRs are involved in regulating pro-inflammatory cytokine and antibody production. Immune cells also frequently express the α2, α5, α6, α7, α9, and α10 nAChR subunits. α7 nAChR-deficient (α7-KO) mice produce more antigen-specific antibody than WT mice, and spleen cells from α7-KO mice produce more TNF-α and IL-6 than WT cells. This suggests that α7 nAChRs are involved in regulating cytokine production and thus modulate antibody production. Evidence also indicates that nicotine modulates immune responses by altering cytokine production and that α7 nAChR signaling contributes to immunomodulation through modification of T cell differentiation. Together, these findings suggest the involvement of both mAChRs and nAChRs in the regulation of immune function. The observation that vagus nerve stimulation protects mice from lethal endotoxin shock led to the notion of a cholinergic anti-inflammatory reflex pathway, and the spleen is an essential component of this anti-inflammatory reflex. Because the spleen lacks direct vagus innervation, it has been postulated that ACh synthesized by a subset of CD4+ T cells relays vagal nerve signals to α7 nAChRs on splenic macrophages, which downregulates TNF-α synthesis and release, thereby modulating inflammatory responses. However, because the spleen is innervated solely by the noradrenergic splenic nerve, confirmation of an anti-inflammatory reflex pathway involving the spleen requires several more hypotheses to be addressed. We will review and discuss these issues in the context of the cholinergic system in immune cells.
Thoracic high-resolution computed tomographic findings in dogs with canine idiopathic pulmonary fibrosis.

OBJECTIVES To identify features of canine idiopathic pulmonary fibrosis (CIPF) using high-resolution computed tomography (HRCT), and to correlate these features with clinical stages of the disease. METHODS Ten dogs with signalment, history and clinical signs highly suggestive of CIPF were investigated. Thoracic radiography, haematology and biochemistry profiles, bronchoscopy and bronchoalveolar lavage and HRCT were performed in each case. The dogs were classified as having mild, moderate or severe stages of the disease based on their clinical presentation and radiographic signs. Features identified by HRCT were correlated with these disease stages. RESULTS HRCT showed a spectrum of pulmonary changes and it was possible to match some of these to the stage of CIPF. CLINICAL SIGNIFICANCE HRCT is used extensively in humans in the diagnosis and treatment planning of idiopathic pulmonary fibrosis. This preliminary study identifies the high-resolution computed tomographic features of CIPF in a small group of dogs. With further work it may be possible to use HRCT as a non-invasive tool for diagnosing, staging and therapeutically monitoring CIPF.