Miracle-dz/UniFAR-FTUs huggingface dataset:
5,6-Dimethylxanthenone-4-acetic Acid (DMXAA) Activates Stimulator of Interferon Gene (STING)-dependent Innate Immune Pathways and Is Regulated by Mitochondrial Membrane Potential*

Background: 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) activates intracellular signaling through uncharacterized pathways similar to those engaged by bacterial pathogens. Results: Mitochondrial targeting agents and absence of STING impair the response to DMXAA in mouse macrophages. Conclusion: Mitochondrial membrane potential is required for optimal response to DMXAA. Significance: This study illustrates that mitochondrial physiology is pivotal in the host response to DMXAA and possibly bacterial pathogens. The chemotherapeutic agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a potent inducer of type I IFNs and other cytokines. This ability is essential for its chemotherapeutic benefit in a mouse cancer model and suggests that it might also be useful as an antiviral agent. However, the mechanism underlying DMXAA-induced type I IFNs, including the host proteins involved, remains unclear. Recently, it was reported that the antioxidant N-acetylcysteine (NAC) decreased DMXAA-induced TNF-α and IL-6, suggesting that oxidative stress may play a role. The goal of this study was to identify host proteins involved in DMXAA-dependent signaling and determine how antioxidants modulate this response. We found that expression of IFN-β in response to DMXAA in mouse macrophages requires the mitochondrial and endoplasmic reticulum resident protein STING. Addition of the antioxidant diphenylene iodonium (DPI) diminished DMXAA-induced IFN-β, but this decrease was independent of both the NADPH oxidase, Nox2, and de novo generation of reactive oxygen species. Additionally, IFN-β up-regulation by DMXAA was inhibited by agents that target the mitochondrial electron transport chain and, conversely, loss of mitochondrial membrane potential correlated with diminished innate immune signaling in response to DMXAA. Up-regulation of Ifnb1 gene expression mediated by cyclic dinucleotides was also impaired by DPI, whereas up-regulation of Ifnb1 mRNA due to cytosolic double-stranded DNA was not. Although both stimuli signal through STING, cyclic dinucleotides interact directly with STING, suggesting that recognition of DMXAA by STING may also be mediated by direct interaction.
Comparative effectiveness of advanced wound dressings for patients with chronic venous leg ulcers: A systematic review

The purpose of this study was to systematically review the literature on the benefits and harms of advanced wound dressings on wound healing, mortality, quality of life, pain, condition of the wound bed, and adverse events for patients with chronic venous leg ulcers as compared with treatment with compression alone. We searched for primary studies in the databases of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature® from January 1980 through July 2012. Each study title, abstract, and full article was evaluated by two independent reviewers. Thirty‐seven studies met our specific search criteria, although most evidence was of low or insufficient quality. Cellular dressings, collagen, and some antimicrobial dressings may improve healing rates of chronic venous leg ulcers vs. compression alone or other dressings. Limited data were available on other outcomes. The poor quality of the literature limits conclusions and necessitates future, well‐conducted studies to evaluate the effectiveness of advanced wound dressings on chronic venous ulcers.
Retinal segmented layers with strong aquaporin-4 expression suffered more injuries in neuromyelitis optica spectrum disorders compared with optic neuritis with aquaporin-4 antibody seronegativity detected by optical coherence tomography

Purpose To evaluate retinal segmented layer alterations in optic neuritis (ON) in an AQP4-Ab seropositive (AQP4-Ab+/ON) cohort and in neuromyelitis optica (NMO) with ON eyes (NMO-ON) compared with an AQP4-Ab seronegative ON (AQP4-Ab−/ON) cohort using optical coherence tomography (OCT). Methods We recruited 109 patients with ON (161 eyes) and 47 healthy controls. All patients with ON were subdivided into three subcohorts: 37 patients (54 eyes) with AQP4-Ab+/ON, 45 patients (65 eyes) with AQP4-Ab−/ON and 27 patients (42 eyes) with NMO-ON. All subjects were evaluated for their peripapillary retinal nerve fibre layer (pRNFL) and inner macular segmented layer using OCT. Results AQP4-Ab+/patients with ON had the same structural injury patterns as patients with NMO-ON, and the injury patterns were distinct from those of AQP4-Ab−/patients with ON. NMO-ON and AQP4-Ab+/ON preferentially damaged the pRNFL (all p=0.000), the macular retinal nerve fibre layer (mRNFL; p=0.000 and 0.032, respectively), and the inner plexiform layer (IPL; p=0.000 and 0.006, respectively) without differences in the retinal ganglion cell layer (p=0.106 and 0.374, respectively) compared with AQP4-Ab−/patients with ON. The thickness of the inner nuclear layer (INL) increased in NMO-ON (p=0.043) compared with that of AQP4-Ab−/ON without a significant difference in AQP4-Ab+/ON versus AQP4-Ab−/ON (p=0.353). When the thickness of the inferior nasal quadrant (NI) of the pRNFL was reduced to ≤46.5 μm (area under the curve 0.772, sensitivity 89.2% and specificity 57.5%) 6 months after ON onset, NMO was considered. Conclusions AQP4-Ab+/ON produced similar structural injury patterns as NMO-ON. The pRNFL, mRNFL and IPL in the two types of ON and the INL in NMO-ON suffered more damage than those in AQP4-Ab−/ON, which could be associated with strong aquaporin-4 expression. The thickness of the NI of the pRNFL could be a potential clue for predicting ON progression to definite NMO.
Effects of Masking-Spectrum Slope and Interaural Phase on Detection of Tones

This study examined the effects of masking-spectrum slopes and of practical interaural-phase configurations on the detection of pure tones, with applications to sonar and related detection systems. Experimental parameters included band-limited Gaussian noise with slopes of 0 dB/octave (white noise) and of −3 dB/octave (pink noise) for monotic (NmSm) and three homophasic (NoSo, Nπ/2Sπ/2 and NπSπ) listening conditions. Stimuli were 250-msec. tonal signals from 125 to 4000 Hz masked in a 5000-Hz-wide noise band having band-pressure levels of 70 and of 90 dB re 2 × 10−4 dyn · cm−3. Critical ratios for three Ss were obtained by the method of tracking. There were no significant differences in detection among homophasic configurations. Two-ear listening was in the order of 1 to 2 dB better than one-ear listening. Detection in pink noise was significantly better than detection in white noise, with differences averaging 4.6 dB at 125 Hz and 0.8 dB at higher frequencies.
Evaluation of the Correlation between CD44, Tumor Prognosis and the 5-Year Survival Rate in Patients with Oral Tongue SCC

Introduction: 90% of the tumors in the head and neck are squamous-cell carcinomas (HNSCC), which have overall 5- year survival rate between 50% -60%. CD44 has been shown to be associated with the prognosis. Materials and Methods: Biopsy specimens of 51 patients with oral tongue SCC were evaluated by Immunohistochemistry (IHC) for the CD44 antibody. Results: There was no significant correlation between CD44 and survival (P=0.77), age (P=0.4), CD44 and lymph node metastasis (P=0.87), sex (P=0.947), smoking (P=0.287) and tumor size (P=0.813). However, there was significant correlation between smoking and survival. Conclusion: There are widespread discrepancies among the findings in the literature regarding the prognosis of CD44 expression in OCSCC. Our study shows that the expression of CD44 is not a marker of aggressive behavior in oral tongue SCC. Consequently, CD44 cannot be considered as handy tool to establish the tumor behavior, prognosis and 5- year survival rate of these tumors.
Analysis of Binary Adherence Data in the Setting of Polypharmacy: A Comparison of Different Approaches

Older community-dwelling adults often take multiple medications for numerous chronic diseases. Nonadherence to these medications can have a large public health impact. Therefore, the measurement and modeling of medication adherence in the setting of polypharmacy is an important area of research. We apply a variety of different modeling techniques (standard linear regression; weighted linear regression; adjusted linear regression; naïve logistic regression; beta-binomial (BB) regression; generalized estimating equations (GEE)) to binary medication adherence data from a study in a North Carolina-based population of older adults, where each medication an individual was taking was classified as adherent or nonadherent. In addition, through simulation we compare these different methods based on Type I error rates, bias, power, empirical 95% coverage, and goodness of fit. We find that estimation and inference using GEE is robust to a wide variety of scenarios and we recommend using this in the setting of polypharmacy when adherence is dichotomously measured for multiple medications per person.
Meditative States Based on Yoga Texts and Their Effects on Performance of a Letter-Cancellation Task

Performance in a six-letter cancellation task was studied in 35 male experienced meditators with experience ranging from 6 to 12 months. Each participant was studied in four sessions, two Meditation and two Control sessions. The Control sessions were (i) Cancalata or nontargeted thinking and (ii) Ekagrata or focusing on a single topic, in this case, meditation. The Meditation sessions were (i) Dharana or focusing on the symbol “OM” and (ii) Dhyana or an effortless single-thought (of OM) state. Ekagrata and dharana differ in that the former involves focusing with multiple thoughts whereas the latter involves focusing with a single thought, i.e., the significance of OM. The net scores on the six-letter cancellation task were significantly higher after a session of Dharana and lower after the Cancalata session, while there was no significant change after Ekagrata and Dhyana sessions. Focusing on the symbol OM in Dharana may favorably influence selective attention, concentration, visual scanning abilities, and a repetitive motor response compared to other sessions.
Antioxidants and Anticoccidial Potential of Aqueous Extract from Various Tree Leaves containing Condensed Tannins

The present study was conducted to determine the antioxidant and anticoccidial properties of aqueous extract from condensed tannins (CT) containing tree leaves (Acacia nilotica, Eugenia jambolana, Ficus religiosa, Leucaenea leucocephala and Psidium guajava). The CT content was estimated by using butanol-Hcl method. The CT extracted from various tree leaves in water as solvents and then lyophilized. The antioxidant potential of aqueous extract from various CT sources was evaluated by using multiple in-vitro colorimetric methods which include 1, 1-Diphenyl-2-picrylhydrazyl (DPPH), total reducing power and hydrogen peroxide assays. Ascorbic acid was used as standard antioxidant in our study. However, anticoccidial efficacy of aqueous extract at different concentration (CT: 1, 2, 3 and 4 mg/ml) from various CT sources was performed using coccidial oocysts sporulation inhibition assay. The DPPH free radical scavenging activity was significantly higher in P. guajava as compared to other sources whereas hydrogen peroxide (H2O2) and reducing power activities were significantly (P<0.05) lower in L. leucocephala compared to other CT sources. Sporulation inhibition (%) of Eimeria spp. was significantly (P<0.05) higher in E. jambolana followed by P. guajava, A. nilotica, L. leucocephla while least in F. religiosa. E. jambolana and P. guajava showed maximum sporulation inhibition activity @ 4 mg/ml. It was concluded that CT extracts of A. nilotica, E. jambolana, F. religiosa, L. leucocephala and P. guajava leaves possess the antioxidant and anti-coccidian property and may be eco-friendly sustainable alternative, natural antioxidant, anti-coccidian agent and/or natural feed additive for organic meat production.
The Retroviral Hypermutation Specificity of APOBEC3F and APOBEC3G Is Governed by the C-terminal DNA Cytosine Deaminase Domain*

The human proteins APOBEC3F and APOBEC3G restrict retroviral infection by deaminating cytosine residues in the first cDNA strand of a replicating virus. These proteins have two putative deaminase domains, and it is unclear whether one or both catalyze deamination, unlike their homologs, AID and APOBEC1, which are well characterized single domain deaminases. Here, we show that only the C-terminal cytosine deaminase domain of APOBEC3F and -3G governs retroviral hypermutation. A chimeric protein with the N-terminal cytosine deaminase domain from APOBEC3G and the C-terminal cytosine deaminase domain from APOBEC3F elicited a dinucleotide hypermutation preference nearly indistinguishable from that of APOBEC3F. This 5′-TC→TT mutational specificity was confirmed in a heterologous Escherichia coli-based mutation assay, in which the 5′-CC→CT dinucleotide hypermutation preference of APOBEC3G also mapped to the C-terminal deaminase domain. An N-terminal APOBEC3G deletion mutant displayed a preference indistinguishable from that of the full-length protein, and replacing the C-terminal deaminase domain of APOBEC3F with AID resulted in an AID-like mutational signature. Together, these data indicate that only the C-terminal domain of APOBEC3F and -3G dictates the retroviral minus strand 5′-TC and 5′-CC dinucleotide hypermutation preferences, respectively, leaving the N-terminal domain to perform other aspects of retroviral restriction.
A Model-Driven Approach for the Design, Implementation, and Execution of Software Development Methods

Los proyectos de desarrollo de software son diversos por naturaleza. Por este motivo, las companias de software se ven forzadas frecuentemente a definir sus metodos de manera interna. Para poder definir metodos de forma efectiva y eficiente, las companias necesitan soluciones sistematicas que esten definidas sobre unos fundamentos metodologicos solidos. Proporcionar estas soluciones es el principal objetivo de la Ingenieria de Metodos. La Ingenieria de Metodos es la disciplina que aborda el diseno, la construccion y la adaptacion de metodos, tecnicas y herramientas para el desarrollo de sistemas de informacion. Durante las dos ultimas decadas, se ha llevado a cabo mucho trabajo de investigacion en esta area. Sin embargo, pese a sus potenciales beneficios, la Ingenieria de Metodos no se aplica ampliamente en contextos industriales. Algunas de las principales causas de esta situacion son la alta complejidad teorica de la Ingenieria de Metodos y la falta de un apropiado soporte software. En esta tesis, pretendemos mitigar algunos de los problemas que afectan a la Ingenieria de Metodos proporcionando una propuesta metodologica innovadora que esta basada en la Ingenieria Dirigida por Modelos (MDE). El uso de MDE permite elevar el nivel de abstraccion, automatizacion y reuso, lo que posibilita una reduccion de la complejidad de nuestra propuesta. Ademas, aprovechando tecnicas de MDE (como por ejemplo el metamodelado, las transformaciones de modelos y los modelos en tiempo de ejecucion), nuestra aproximacion da soporte a tres fases del ciclo de vida de la Ingenieria de Metodos: diseno, implementacion y ejecucion. Esto es a diferencia de las propuestas existentes, las cuales, por lo general, solo dan soporte a una de estas fases. Con el objetivo de proporcionar soporte software para nuestra propuesta, implementamos una herramienta CAME (Computer-Aided Method Engineering) llamada MOSKitt4ME. Para garantizar que MOSKitt4ME proporcionaba la funcionalidad necesaria, definimos un conjunto de requisitos funcionales como paso previo al desarrollo de la herramienta. Tras la defincion de estos requisitos, definimos la arquitectura de la herramienta CAME y, finalmente, implementamos la arquitectura en el contexto de Eclipse. El trabajo desarrollado en esta tesis se evaluo por medio de un estudio donde participaron usuarios finales. En este estudio, MOSKitt4ME se evaluo por medio del Technology Acceptance Model (TAM) y del metodo Think Aloud. Mientras que el TAM permitio medir utilidad y facilidad de uso de forma subjetiva, el metodo Think Aloud permitio analizar estas medidas objetivamente. En general, los resultados obtenidos fueron favorables. MOSKitt4ME fue valorado de forma positiva en cuanto a utilidad y facilidad de uso percibida; ademas, obtuvimos resultados positivos en cuanto al rendimiento objetivo de los usuarios y la dificultad experimentada.
The drunk, the reformer and the teacher: agonistic poetics and the construction of persona in the comic poets of the fifth century

Although the role of competition in Greek cultural and social practices has been well documented and studied, it is only in the last decades that the extent to which it permeates Athenian drama has been realised. The element of competition in Athenian dramatic performances is now widely used as an interpretative tool, especially in Old comedy, where the competitive conditions of performance are overtly articulated. As research on the fragmentary comic poets proliferates, Aristophanes' rivals have become a far more visible element in the scenery of Old Attic comedy and, as a result, the fiercely competitive dimension of comic performances is more easily traced. We are now able to ask questions from new perspectives, and understand better such issues as authorial collaboration, charges of plagiarism, claims of degeneration and decline in the quality of plays and their authors, as well as illustrate the enormous role of audience reception in the interpretation of Old comedy. Aristophanes' bombastic and self-righteous comments regarding himself and his poetry are now read in a more nuanced manner, as a competitive poetic strategy which constructs a fictionalised ‘Aristophanes’.
Bird-keeping in Indonesia: conservation impacts and the potential for substitution-based conservation responses

Bird-keeping is an extremely popular pastime in Indonesia, where there is a thriving internal market in both wild-caught and captive-bred birds. However, little is known about whether the scale of bird-keeping represents a genuine conservation threat to native populations. Here we present the results of the largest ever survey of bird-keeping among households in Indonesia's five major cities. Birds were found to be urban Indonesia's most popular pet (kept by 21.8% of survey households) and we conservatively estimate that as many as 2.6 million birds are kept in the five cities sampled. Of bird-keeping households, 78.5% kept domestic species and/or commercially bred species and 60.2% kept wild-caught birds that we classified into three conservation categories: native songbirds, native parrots and imported songbirds. Compared to non-bird owners, households keeping wild-caught birds in all three conservation categories were richer and better educated, whereas households owning commercially-bred species were richer but not better educated and households keeping domestic species did not differ in educational or socio-economic status. We conclude that bird-keeping in Indonesia is at a scale that warrants a conservation intervention and that promoting commercially-bred alternatives may be an effective and popular solution.
Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function.

Insulin, the central hormone controlling the utilization of fuel, is initially synthesized in pancreatic beta cells as its relatively inactive precursor, proinsulin. A series of enzymes that process prohormones act on proinsulin to produce mature insulin and C peptide. Abnormalities in the secretory products of beta cells are a rare but well-documented cause of impairment in glucose tolerance and hyperinsulinemia.1 Two specific syndromes have been defined. First, mutations in the insulin gene that lead to the production of biologically ineffective insulin have been described in several families.2–4 All cases described to date have involved heterozygotes who produce normal insulin .
DTI at long diffusion time improves fiber tracking

While diffusion‐tensor‐imaging tractography provides remarkable in vivo anatomical connectivity of the central nervous system, the majority of DTI studies to date are predominantly limited to tracking large white‐matter fibers. This study investigated DTI tractography using long diffusion time (tdiff) to improve tracking of thinner fibers in fixed rhesus monkey brains. Stimulated Echo Acquisition Mode (STEAM) sequence on a 3T Siemens TRIO was modified to include a diffusion module. DTI was acquired using STEAM with tdiff of 48 and 192 ms with matched signal‐to‐noise ratios (SNR). Comparisons were also made with the conventional double‐spin echo (DSE) at a short tdiff of 45 ms. Not only did the fractional anisotropy increase significantly with the use of long diffusion time, but directional entropy measures indicated that there was an increased coherence amongst neighboring tensors. Further, the magnitude of the major eigenvector was larger at the tdiff = 192 ms as compared to the short tdiff. Probabilistic connectivity maps at long tdiff showed larger areas of connectivity with the use of long diffusion time, which traversed deeper into areas of low anisotropy. With tractography, it was found that the length of the fibers, increased by almost 10% in the callosal fibers that branch into the paracentral gyrus, the precentral gyrus and the post central gyrus. A similar increase of about 20% was observed in the fibers of the internal capsule. These findings offer encouraging data that DTI at long diffusion time could improve tract tracing of small fibers in areas of low fractional anisotropy (FA), such as at the interfaces of white matter and grey matter. Copyright © 2010 John Wiley & Sons, Ltd.
Peer Victimization and Psychosocial Adjustment in Children: Current Knowledge and Future Directions

Childhood peer victimization is the experience of being a target of peers’ aggressive behavior. Peer victimization is a common occurrence and has been concurrently and prospectively linked to significant psychological distress. This paper provides a review of the extant literature on the relationship between peer victimization and psychosocial adjustment in nonclinical and pediatric populations. Clinical applications of this literature, as well as directions for future study, are presented.
Effects of inhibitors of hydrogen sulphide synthesis on rat colonic motility

BACKGROUND AND PURPOSE The role of hydrogen sulphide (H2S) as a putative endogenous signalling molecule in the gastrointestinal tract has not yet been established. We investigated the effect of D,L‐propargylglycine (PAG), an inhibitor of cystathionine γ‐lyase (CSE), amino‐oxyacetic acid (AOAA) and hydroxylamine (HA), inhibitors of cystathionine β‐synthase (CBS) on rat colonic motility.
Stabilization of discrete time linear systems by static output feedback

This note proposes a systematic approach for the static output feedback control design for discrete time linear systems. It is shown that if the open loop system satisfies some particular structural conditions, a static output feedback gain can be calculated easily, using a formula only involving the original system matrices. Among the conditions the system has to satisfy, the stronger relies on a minimum phase argument. Square and nonsquare systems are considered.