Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitric Oxide Inhibits the Transcription Repressor Yin-Yang 1 Binding Activity at the Silencer Region of the Fas Promoter: A Pivotal Role for Nitric Oxide in the Up-Regulation of Fas Gene Expression in Human Tumor Cells1

NO has been increasingly implicated in control of the transcriptional machinery and serves as an intracellular second messenger to modify gene expression. We have demonstrated that NO up-regulated Fas receptor expression in ovarian carcinoma cell lines, albeit the mechanism involved is not known. Thus, we hypothesized that NO, directly or indirectly, may modify the transcriptional machinery that is responsible for the increased expression of the Fas gene. We examined the effect of NO on Fas gene expression using a Fas promoter-driven luciferase reporter system. Transient transfection of AD10 cells with pGL-3-FasP demonstrated that the IFN-γ-dependent NO generation increases the trans-activation of the Fas promoter, and this increase was blocked by the NOS inhibitor (NG-monomethyl-l-arginine), but could be restored by the addition of the NO donor S-nitroso-N-acetylpenicillamine. Systematic deletion of the Fas promoter revealed that the functional region responsible for the NO-mediated effect was located at the silencer region, suggesting that NO may be responsible for the disruption of a repressor mechanism. We demonstrate that NO up-regulates the expression of the Fas receptor on AD10 cells via the specific inactivation of the transcription repressor yin-yang 1 DNA binding activity to the silencer region of the Fas promoter. These findings reveal a new mechanism of NO-mediated gene regulation by interfering with a repressor transcription factor at the silencer region of the Fas promoter.
Cdk2‐dependent phosphorylation of Id2 modulates activity of E2A‐related transcription factors

The helix–loop–helix (HLH) protein Id2 is thought to affect the balance between cell growth and differentiation by negatively regulating the function of basic‐helix–loop–helix (bHLH) transcription factors. Id2 acts by forming heterodimers that are unable to bind to specific (E‐box) DNA sequences. Here we show that this activity can be overcome by phosphorylation of a serine residue within a consensus target site for cyclin‐dependent kinases (Cdks). In vitro, Id2 can be phosphorylated by either cyclin E‐Cdk2 or cyclin A‐Cdk2 but not by cyclin D‐dependent kinases. Analogous phosphorylation occurs in serum‐stimulated human diploid fibroblasts at a time in late G1 consistent with the appearance of active cyclin E–Cdk2. The phosphorylation of Id2 in these cells correlates with the restoration of a distinct E‐box‐dependent DNA‐binding complex, suggesting that the levels of this complex are modulated by both the abundance and phosphorylation status of Id2. These data provide a link between cyclin‐dependent kinases and bHLH transcription factors that may be critical for the regulation of cell proliferation and differentiation.
Finite Element Modeling of Multi-Walled Carbon Nanotubes

Finite element modeling is used to simulate carbon nanotubes, CNTs. A three-dimensional finite element (FE) model for Armchair, Chiral and Zigzag single-walled carbon nanotube (SWCNT), double-walled carbon nanotube (DWCNT) and multi-walled carbon nanotube (MWCNT) is presented here. The model development is based on the assumption that carbon nanotubes, when subjected to loading, behave like space-frame structures. The bonds between the carbon atoms are considered as connecting load-carrying members, while the carbon atoms themselves as joints of the members. The nodes are placed at the locations of the carbon atoms and the bonds between them are modeled using threedimensional elastic beam elements. Young modulus is finally calculated. The Young's modulus of Chiral configuration is found to be the largest among the three configurations, while that of the Zigzag is the lowest. Index Term-finite element method, nanostructured materials, carbon nanotubes, CNT, multi -walled carbon
Effect of Ag additions on the Bi1.6Pb0.4Sr 2Co1.8Ox thermoelectric properties

This research has been supported by the Spanish Ministry of Science and Innovation (Project MAT2008-00429) and the Universidad de Zaragoza (Project UZ2011-TEC-03). The authors wish to thank the Gobierno de Aragon (Consolidated Research Groups T87 and T12) for financial support and to C. Gallego, C. Estepa and J. A. Gomez for their technical assistance. Sh. Rasekh acknowledges a JAE-PreDoc2010 grant from the CSIC.
New developments in localized scleroderma

Purpose of reviewLocalized scleroderma, also known as morphea, is the most frequent form of scleroderma in childhood. Early diagnosis, appropriate assessment and effective treatment may improve the long-term outcome. Recent findingsRecent studies, regarding the microchimerism theory or the mechanism of action of phototherapy, have yielded important information on the disease etiopathogenesis. Others have added interesting contributions on new outcome measures for the disease assessment and for the development of future therapeutic trials. Previous results, using methotrexate and phototherapy, have been confirmed. A successful use of bosentan, an endothelin receptor antagonist with vasodilatative and antifibrotic properties for refractory cutaneous ulcerations in pansclerotic morphea, opens new horizons of treatment. SummaryStudies over the past year highlight the role of some outcome measures in the disease assessment and monitoring, with important implications both for the clinical practice and future clinical trials.
Control of Viremia and Prevention of AIDS following Immunotherapy of SIV-Infected Macaques with Peptide-Pulsed Blood

Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIVmac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably ∼10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans.
Identifying Autism in a Brief Observation

BACKGROUND: Pediatricians, neurologists, and geneticists are important sources for autism surveillance, screening, and referrals, but practical time constraints limit the clinical utility of behavioral observations. We analyzed behaviors under favorable conditions (ie, video of autism evaluations reviewed by experts) to determine what is optimally observable within 10-minute samples, asked for referral impressions, and compared these to formal screening and developmental testing results. METHODS: Participants (n = 42, aged 15 to 33 months) were typically developing controls and children who screened positive during universal autism screening within a large community pediatric practice. Diagnostic evaluations were performed after screening to determine group status (autism, language delay, or typical). Licensed psychologists with toddler and autism expertise, unaware of diagnostic status, analyzed two 10-minute video samples of participants’ autism evaluations, measuring 5 behaviors: Responding, Initiating, Vocalizing, Play, and Response to Name. Raters were asked for autism referral impressions based solely on individual 10-minute observations. RESULTS: Children who had autism showed more typical behavior (89% of the time) than atypical behavior (11%) overall. Expert raters missed 39% of cases in the autism group as needing autism referrals based on brief but highly focused observations. Significant differences in cognitive and adaptive development existed among groups, with receptive language skills differentiating the 3 groups. CONCLUSIONS: Brief clinical observations may not provide enough information about atypical behaviors to reliably detect autism risk. High prevalence of typical behaviors in brief samples may distort clinical impressions of atypical behaviors. Formal screening tools and general developmental testing provide critical data for accurate referrals.
An insider's guide to the microtubule cytoskeleton of Giardia

Giardia intestinalis is a zoonotic, parasitic protist with a complex microtubule cytoskeleton critical for motility, attachment, intracellular transport, cell division and transitioning between its two life cycle stages – the cyst and the trophozoite. This review focuses on the structures of the primary elements of the microtubule cytoskeleton and cytoskeletal dynamics throughout this complex giardial life cycle. The giardial cytoskeleton has both highly dynamic elements and more stable MT structures, including several novel structures like the ventral disc that change conformation via unknown mechanisms. While our knowledge of the giardial cytoskeleton is primarily cytological, the completed Giardia genome and recently developed reverse genetic tools affords an opportunity to uncover the mechanisms of Giardia's cytoskeletal dynamics. Fundamental areas of giardial cytoskeletal biology remain to be explored, including high resolution imaging and compositional characterization of cytoskeletal structures required for elucidating the molecular mechanisms of cytoskeletal functioning.
Quality Driven Frame Rate Optimization for Rate Constrained Video Encoding

Video quality under rate constraint is mainly controlled by the frame rate and the quantization parameter. This work proposes a mechanism to obtain the optimal frame rate that maximizes video quality under rate constraint. Based on an objective metric of video quality that can reflect subjective quality, this work first proposes a video quality-frame rate-rate constraint model. Second, the relationship between model parameters and video characteristics is formulized. Finally, this work proposes an efficient frame rate optimization mechanism. Experimental results show that the optimal frame rate estimated by our mechanism is identical to the actual optimal frame rate under most bit rate constraints for both training sequences and new test sequences. In addition, the quality loss caused by the estimation error is generally limited within 0.8 dB in our experiments.
Nature of curvature coupling of amphiphysin with membranes depends on its bound density

Cells are populated by a vast array of membrane-binding proteins that execute critical functions. Functions, like signaling and intracellular transport, require the abilities to bind to highly curved membranes and to trigger membrane deformation. Among these proteins is amphiphysin 1, implicated in clathrin-mediated endocytosis. It contains a Bin-Amphiphysin-Rvs membrane-binding domain with an N-terminal amphipathic helix that senses and generates membrane curvature. However, an understanding of the parameters distinguishing these two functions is missing. By pulling a highly curved nanotube of controlled radius from a giant vesicle in a solution containing amphiphysin, we observed that the action of the protein depends directly on its density on the membrane. At low densities of protein on the nearly flat vesicle, the distribution of proteins and the mechanical effects induced are described by a model based on spontaneous curvature induction. The tube radius and force are modified by protein binding but still depend on membrane tension. In the dilute limit, when practically no proteins were present on the vesicle, no mechanical effects were detected, but strong protein enrichment proportional to curvature was seen on the tube. At high densities, the radius is independent of tension and vesicle protein density, resulting from the formation of a scaffold around the tube. As a consequence, the scaling of the force with tension is modified. For the entire density range, protein was enriched on the tube as compared to the vesicle. Our approach shows that the strength of curvature sensing and mechanical effects on the tube depends on the protein density.
Microstructure and fatigue strength of high performance gear steels

Observations on some steels used in high performance gears are presented in this thesis. The object was to understand how microstructure and residual stress influenced mechanical properties, particularly fatigue strength. The investigations were carried out using fatigue testing, metallographic techniques, shot peening, hardness testing and Xray diffraction to determine residual stress and the amount of retained austenite. The work is divided into two main parts. In the first part, the opportunity was taken of investigating a batch of case-carburised gears manufactured from 17CrNiMo6 steel that contained an abnormally high level of retained austenite. The benefits or otherwise of retained austenite is a matter of some controversy in the literature and this was an opportunity of testing the effect of high retained austenite in gears. In the second part, the properties of a recently formulated through hardening steel was investigated. The steel is inexpensive and capable of being fully hardened by air-cooling. It is believed that use of the material could reduce the cost of gear manufacture by eliminating the carburisation process, oil quenching and the subsequent need to correct distortions that arise from quenching. Gears were manufactured using l7CrNiMo6 steel. After carburization, one batch was found to have an abnormally high level of retained austenite (40 to 60%). Normally, gears with this level of retained austenite would be rejected. Nevertheless, gears from this batch were found to have surface and bending fatigue strengths that were not very different from those with much lower retained austenite contents. Despite the fact that the material is relatively soft, it was found that a very thin surface layer had hardened during back-to-back gear testing, probably by strain-induced transformation of the retained austenite. It was deduced that this thin layer of hardened material is sufficient to maintain a good level of surface contact fatigue strength. The second part of the work includes a basic study of the through-hardening steel. The study includes heat treatment and hardness, estimation of fracture toughness and the development of residual stress during heat treatment. Specialised standing contact fatigue (SCF) tests were also done using this material. The SCF test consists of cyclic loading of a hard ball in contact with the surface of the specimen, which is meant to simulate asperity contact in surface contact fatigue. Radial cracks or ring cracks or both are nucleated just outside the indentation circle in these tests, depending on the load and the development of plasticity. The stresses near the indentation were modelled using Finite Element analysis and were found to be consistent with the experimental results. Finally, the effect of residual compressive stress induced by shot peeing was studied using the SCF test. It was found that shot peening suppressed the formation of radial cracks.
Purification and properties of an acetylxylan esterase from Fibrobacter succinogenes S85

An acetylxylan esterase (EC 3.1.1.6) was purified to apparent homogeneity from the nonsedimentable extracellular culture fluid of Fibrobacter succinogenes S85 grown on cellulose. This enzyme had an apparent molecular mass of 55 kDa and an isoelectric point of 4.0. The temperature and pH optima were 45 degrees C and 7.0, respectively. The apparent Km and Vmax were 2.7 mM and 9,100 U/mg, respectively, for the hydrolysis of alpha-naphthyl acetate. The enzyme cleaved acetyl residues from birchwood acetylxylan but did not hydrolyze carboxymethylcellulose, larchwood xylan, ferulic acid-arabinose-xylose polymer, p-nitrophenyl-alpha-L-arab-inofuranoside, or longer-chain naphthyl fatty acid esters. The esterase enzyme may play a role in enhancing hemicellulose degradation by F. succinogenes, thereby allowing it greater access to cellulose present in forage cell walls.
Genotype-dependent serologic reactivities in patients infected with hepatitis C virus in the United States.

OBJECTIVE To evaluate the serologic reactivities in patients infected with different hepatitis C virus (HCV) genotypes to four HCV proteins that are components of the second-generation recombinant immunoblot assay. MATERIAL AND METHODS Serum samples from 36 patients with chronic HCV infection were obtained. RNA was extracted by using chaotropic lysis and isopropanol precipitation. Reverse-transcriptase polymerase chain reaction of the NS-5 region was performed, followed by automated single-pass dideoxy sequencing of desalted amplification products. Classification of isolated HCV subtypes was based on Simmonds' system. All samples were tested for antibodies to proteins 5-1-1, C100-3, C33c, and C22-3 with the second-generation recombinant immunoblot assay. RESULTS Reactivity to protein 5-1-1 was significantly lower for patients with genotypes 2b and 3a than for those infected with HCV types 1a or 1b (P < 0.05). Antibody reactivity to the C100-3 protein was also reduced in patients infected with HCV types 2b and 3a. CONCLUSION These data indicate that the genotype-dependent differences in serologic reactivities are substantial among patients with chronic HCV infection.
Analgesic effect of intrathecal bumetanide is accompanied by changes in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain

Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the specific sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression increased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These findings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassium-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassium-chloride co-transporter 1.
Monte Carlo analysis of parameter uncertainty in matrix models for the weed Cirsium vulgare

Summary 1. Parameter uncertainty challenges the use of matrix models because it violates key assumptions underlying elasticity analyses. We have developed a matrix model to compare Monte Carlo methods with elasticity analyses for estimation of the relative importance of factors in the asymptotic population growth rate, λ , of Cirsium vulgare (spear thistle) in Nebraska, USA. 2. We calculated λ for a base model using 11 parameter estimates available for Nebraska populations plus eight extracted from the literature, causing parameter uncertainty. We then calculated λ for 10 000 alternative models using Monte Carlo parameter estimation; parameters were drawn from the full range of each parameter in the literature and partial rank correlation analysis (PRCC) was used to order the parameters by the magnitude of their effect on λ . 3. Monte Carlo analysis found that insect floral herbivory, affecting the regeneration transition, was the most important parameter affecting λ , whereas elasticity analyses suggested that the transition from small to medium size was the most significant. Statistical comparison, using PRCC vs. lower level elasticity (LLE), showed that the Monte Carlo analysis provided a more accurate assessment. 4. As λ > 1 in 99% of the model runs even with significant floral herbivory, we added two parameters influenced by weed management (probability of large thistles dying without producing seed and proportion of seeds that failed to germinate). Simulations that included reductions in these parameters, along with floral herbivory, led to λ < 1 in 17% of the runs, suggesting these three factors interact to produce the low densities observed for this invasive thistle in our study area. 5. Synthesis and applications. This study demonstrates the utility of the Monte Carlo approach for modelling weed dynamics with parameter uncertainty and multiple, potentially interacting, parameters. Invasive population growth by C. vulgare could be limited by a combination of weed management practices and the biotic resistance imposed by native floral herbivores.