487 research outputs found

    Mechanical Properties and Durability of Latex-Modified Fiber-Reinforced Concrete: A Tunnel Liner Application

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    This study assessed the mechanical properties and durability of latex-modified fiber-reinforced segment concrete (polyolefin-based macrosynthetic fibers and hybrid fiber-macrosynthetic fiber and polypropylene fiber) for a tunnel liner application. The tested macrosynthetic fiber-reinforced concrete has a better strength than steel fiber-reinforced concrete. The tested concrete with blast furnace slag has a higher chloride ion penetration resistance (less permeable), but its compressive and flexural strengths can be reduced with blast furnace slag content increase. Also, the hybrid fiber-reinforced concrete has higher compressive strength, flexural strength, chloride ion water permeability resistance, impact resistance, and abrasion resistance than the macrosynthetic fiber-reinforced concrete. The modified fiber improved the performance of concrete, and the hybrid fiber was found to control the formation of micro- and macrocracks more effectively. Therefore, overall performance of the hybrid fiber-reinforced concrete was found superior to the other fiber-reinforced concrete mixes tested for this study. The test results also indicated that macrosynthetic fiber could replace the steel fiber as a concrete reinforcement

    The N-Terminal Methionine of Cellular Proteins as a Degradation Signal

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    The Arg/N-end rule pathway targets for degradation proteins that bear specific unacetylated N-terminal residues while the Ac/N-end rule pathway targets proteins through their N^α-terminally acetylated (Nt-acetylated) residues. Here, we show that Ubr1, the ubiquitin ligase of the Arg/N-end rule pathway, recognizes unacetylated N-terminal methionine if it is followed by a hydrophobic residue. This capability of Ubr1 expands the range of substrates that can be targeted for degradation by the Arg/N-end rule pathway because virtually all nascent cellular proteins bear N-terminal methionine. We identified Msn4, Sry1, Arl3, and Pre5 as examples of normal or misfolded proteins that can be destroyed through the recognition of their unacetylated N-terminal methionine. Inasmuch as proteins bearing the Nt-acetylated N-terminal methionine residue are substrates of the Ac/N-end rule pathway, the resulting complementarity of the Arg/N-end rule and Ac/N-end rule pathways enables the elimination of protein substrates regardless of acetylation state of N-terminal methionine in these substrates

    Directly converted patient-specific induced neurons mirror the neuropathology of FUS with disrupted nuclear localization in amyotrophic lateral sclerosis

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    Background Mutations in the fused in sarcoma (FUS) gene have been linked to amyotrophic lateral sclerosis (ALS). ALS patients with FUS mutations exhibit neuronal cytoplasmic mislocalization of the mutant FUS protein. ALS patients fibroblasts or induced pluripotent stem cell (iPSC)-derived neurons have been developed as models for understanding ALS-associated FUS (ALS-FUS) pathology; however, pathological neuronal signatures are not sufficiently present in the fibroblasts of patients, whereas the generation of iPSC-derived neurons from ALS patients requires relatively intricate procedures. Results Here, we report the generation of disease-specific induced neurons (iNeurons) from the fibroblasts of patients who carry three different FUS mutations that were recently identified by direct sequencing and multi-gene panel analysis. The mutations are located at the C-terminal nuclear localization signal (NLS) region of the protein (p.G504Wfs*12, p.R495*, p.Q519E): two de novo mutations in sporadic ALS and one in familial ALS case. Aberrant cytoplasmic mislocalization with nuclear clearance was detected in all patient-derived iNeurons, and oxidative stress further induced the accumulation of cytoplasmic FUS in cytoplasmic granules, thereby recapitulating neuronal pathological features identified in mutant FUS (p.G504Wfs*12)-autopsied ALS patient. Importantly, such FUS pathological hallmarks of the patient with the p.Q519E mutation were only detected in patient-derived iNeurons, which contrasts to predominant FUS (p.Q519E) in the nucleus of both the transfected cells and patient-derived fibroblasts. Conclusions Thus, iNeurons may provide a more reliable model for investigating FUS mutations with disrupted NLS for understanding FUS-associated proteinopathies in ALS

    Ocular vestibular evoked myogenic potentials induced by air-conducted sound in patients with acute brainstem lesions

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    h i g h l i g h t s More than half of the patients with brainstem lesions showed abnormal air-conducted oVEMPs. The main lesion locations responsible for abnormal oVEMPs were the upper medial medulla, and the dorsomedial tegmentum of the pons and midbrain. Areas of the medial longitudinal fasciculus, the crossed ventral tegmental tracts and the oculomotor nucleus may carry the otolith-ocular signals required for oVEMP formation. a b s t r a c t Objective: The ocular vestibular-evoked myogenic potential (oVEMP), a recently documented otolithocular reflex, is considered to reflect the central projections of the primary otolithic afferent fibers to the oculomotor nuclei. The aim of our study is to define air-conducted sound oVEMP abnormality in patients with acute brainstem lesions and to determine the brainstem structures involved in the generation of oVEMPs. Methods: In response to air-conducted tone burst sounds (ACS), oVEMP was measured in 52 patients with acute brainstem lesions. Individualized brainstem lesions were analyzed by means of MRI-based voxel-wise lesion-behavior mapping, and the probabilistic lesion maps were constructed. Results: More than half (n = 28, 53.8%) of the patients with acute brainstem lesions showed abnormal oVEMP in response to ACS. The majority of patients with abnormal oVEMPs had lesions in the dorsomedial brainstem that contains the medial longitudinal fasciculus (MLF), the crossed ventral tegmental tract (CVTT), and the oculomotor nuclei and nerves. Conclusion: MLF, CVTT, and the oculomotor nuclei and nerves appear to be responsible for otolith-ocular responses in the brainstem. Significance: Complemented to cervical VEMP for the uncrossed otolith-spinal function, oVEMP to ACS may be applied to evaluate the crossed otolith-ocular function in central vestibulopathies

    Late Simultaneous Presentation of Left Ventricular Pseudoaneurysm and Tricuspid Regurgitation after Blunt Chest Trauma

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    A 32-yr-old man developed progressive exertional dyspnea 4 yr after blunt chest trauma due to an automobile accident. Two-dimensional echocardiography and computed-tomographic coronary angiography demonstrated a large pseudoaneurysm of the left ventricle and severe tricuspid regurgitation. The patient underwent successful surgical exclusion of the pseudoaneurysm by endoaneurysmal patch closure and repair of the tricuspid valve regurgitation. To the best of our knowledge, this is the first case of these 2 different pathologies presenting late simultaneously after blunt chest trauma and successful surgical repairs in the published literature

    A Case of Postoperative Tuberculous Spondylitis with a Bizarre Course

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    Postoperative infections following spine surgery are usually attributable to bacterial organisms. Staphylococcus aureus is known to be the most common single pathogen leading to this infection, and the number of infections caused by methicillin-resistant Staphylococcus aureus is increasing. However, there is a paucity of literature addressing postoperative infection with Mycobacterium tuberculosis. We encountered a case of tuberculous spondylitis after spine surgery. A man had fever with low back pain three weeks after posterior interbody fusion with instrumentation for a herniated intervertebral disc at the L4-L5 level. He had been treated with antibiotics for an extended period of time under the impression that he had a bacterial infection, but his symptoms and laboratory data had not improved. Polymerase chain reaction for Mycobacterium tuberculosis turned out to be positive. The patient's symptoms finally improved when he was treated with antituberculosis medication
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