1,729 research outputs found

    Bridge Pile Response to Lateral Soil Movement Induced by Installation of Controlled Modulus Columns

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    © 2016 The Authors. Published by Elsevier B.V. Controlled modulus columns (CMC) for ground improvement are installed using a hollow stem displacement auger to induce lateral soil displacement effect, followed by grout injection. While the method reduces spoils, the excessive lateral soil displacement may damage adjacent structures. Although there has been growing interest in quantifying such effects, only a handful of studies have been attempted. This paper presents the results of a numerical investigation on the CMC installation effect on an existing bridge pile using the three-dimensional finite difference software package FLAC3D. It has been found that when the CMC is long and the existing bridge pile is slender, the pile bending moment and pile lateral movement, induced by the CMC installation effect, can be significant

    Spontaneous expectoration of pulmonary metastases in a child with osteogenic sarcoma

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148355/1/pbc27611.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148355/2/pbc27611_am.pd

    Molecular basis of FIR-mediated c-myc transcriptional control

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    The far upstream element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream of the c-myc promoter. Then, FBP recruits its specific repressor (FIR), which acts as an on/off transcriptional switch. Here we describe the molecular basis of FIR recruitment, showing that the tandem RNA recognition motifs of FIR provide a platform for independent FUSE DNA and FBP protein binding and explaining the structural basis of the reversibility of the FBP-FIR interaction. We also show that the physical coupling between FBP and FIR is modulated by a flexible linker positioned sequentially to the recruiting element. Our data explain how the FUSE system precisely regulates c-myc transcription and suggest that a small change in FBP-FIR affinity leads to a substantial effect on c-Myc concentration.MRC Grant-in-aid U11757455

    Bilateral simultaneous rupture of the quadriceps tendon in a patient with psoriasis: a case report and review of the literature

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    <p>Abstract</p> <p>Introduction</p> <p>Bilateral quadriceps tendon rupture is not common in the absence of systemic disease. Patients with chronic systemic diseases such as uremia and systemic lupus erythematosus and patients who are being treated with systemic steroids or local steroid injections are more prone to tendon rupture. The tendon can rupture spontaneously or as a result of trauma. We report an unusual case of simultaneous bilateral traumatic quadriceps tendon rupture in a patient with psoriasis who was being treated with topical steroid preparations.</p> <p>Case presentation</p> <p>A 57-year-old Caucasian man with a known history of psoriasis, for which he was being treated with topical steroid preparations, presented to our hospital with clinical signs of bilateral quadriceps tendon rupture after he fell while walking down stairs. The diagnosis was confirmed by bilateral ultrasound scans of the thighs. The patient underwent surgery to repair both quadriceps tendons. Post-operatively, the patient was immobilized first in bilateral cylinder casts for six weeks, then in knee braces for the next four weeks. His knees were actively mobilized during physiotherapy.</p> <p>Conclusion</p> <p>Bilateral quadriceps tendon rupture is a rare occurrence in patients with psoriasis who are being treated with topical steroids.</p

    Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

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    Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

    Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

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    Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

    Attention to Speech-Accompanying Gestures: Eye Movements and Information Uptake

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    There is growing evidence that addressees in interaction integrate the semantic information conveyed by speakers’ gestures. Little is known, however, about whether and how addressees’ attention to gestures and the integration of gestural information can be modulated. This study examines the influence of a social factor (speakers’ gaze to their own gestures), and two physical factors (the gesture’s location in gesture space and gestural holds) on addressees’ overt visual attention to gestures (direct fixations of gestures) and their uptake of gestural information. It also examines the relationship between gaze and uptake. The results indicate that addressees’ overt visual attention to gestures is affected both by speakers’ gaze and holds but for different reasons, whereas location in space plays no role. Addressees’ uptake of gesture information is only influenced by speakers’ gaze. There is little evidence of a direct relationship between addressees’ direct fixations of gestures and their uptake

    Anticancer Gene Transfer for Cancer Gene Therapy

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    Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

    Comparison of Statistical Population Reconstruction Using Full and Pooled Adult Age-Class Data

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    BACKGROUND: Age-at-harvest data are among the most commonly collected, yet neglected, demographic data gathered by wildlife agencies. Statistical population construction techniques can use this information to estimate the abundance of wild populations over wide geographic areas and concurrently estimate recruitment, harvest, and natural survival rates. Although current reconstruction techniques use full age-class data (0.5, 1.5, 2.5, 3.5, … years), it is not always possible to determine an animal's age due to inaccuracy of the methods, expense, and logistics of sample collection. The ability to inventory wild populations would be greatly expanded if pooled adult age-class data (e.g., 0.5, 1.5, 2.5+ years) could be successfully used in statistical population reconstruction. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the performance of statistical population reconstruction models developed to analyze full age-class and pooled adult age-class data. We performed Monte Carlo simulations using a stochastic version of a Leslie matrix model, which generated data over a wide range of abundance levels, harvest rates, and natural survival probabilities, representing medium-to-big game species. Results of full age-class and pooled adult age-class population reconstructions were compared for accuracy and precision. No discernible difference in accuracy was detected, but precision was slightly reduced when using the pooled adult age-class reconstruction. On average, the coefficient of variation (i.e., SE(θ)/θ) increased by 0.059 when the adult age-class data were pooled prior to analyses. The analyses and maximum likelihood model for pooled adult age-class reconstruction are illustrated for a black-tailed deer (Odocoileus hemionus) population in Washington State. CONCLUSIONS/SIGNIFICANCE: Inventorying wild populations is one of the greatest challenges of wildlife agencies. These new statistical population reconstruction models should expand the demographic capabilities of wildlife agencies that have already collected pooled adult age-class data or are seeking a cost-effective method for monitoring the status and trends of our wild resources
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