1,964 research outputs found

    Experience vs. Age in the Bumblebee, Bombus huntii

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    Technical communication. Perspectives for the Eighties, part 2

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    The importance of technical writing as a separate discipline is suggested. Some specific areas addressed were: technical writing skills industry needs, definitions of technical writing, the hows and whys of inhouse writing, and the nature of the composing process in technical comunication

    Technical Communication: Perspectives for the Eighties, Part 1. Proceedings of the Technical Communications Sessions at the 32Nd Annual Meeting of the Conference on College Composition and Communication

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    Proceeding of the technical communication sessions at the 32nd annual meeting of the Conference on College Composition and Communication held in Dallas, Texas, March 26-28, 1981 are summarized. The proceeding suggest that technical communication has become an important subfield and is becoming an intrinsic part of many undergraduate curricula. Technical communication as a separate discipline, however, is relatively new. For that reason, proceedings that can make current research available as quickly as possible are suggested for preparation. The following topics were addressed: (1) a history and definition of technical writing, (2) the case method is technical communication (3) teaching technical writing (4) oral communication and rhetorical theory, and (5) new approaches in and practical applications of technical writing

    In Vivo Dissection of the Intrinsically Disordered Receptor Domain of Tim23

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    In the intermembrane space (IMS) of mitochondria, the receptor domain of Tim23 has an essential role during translocation of hundreds of different proteins from the cytosol via the TOM and TIM23 complexes in the outer and inner membranes, respectively. This intrinsically disordered domain, which can even extend into the cytosol, was shown, mostly in vitro, to interact with several subunits of the TOM and TIM23 complexes. To obtain molecular understanding of this organizational hub in the IMS, we dissected the IMS domain of Tim23 in vivo. We show that the interaction surface of Tim23 with Tim50 is larger than previously thought and reveal an unexpected interaction of Tim23 with Pam17 in the IMS, impairment of which influences their interaction in the matrix. Furthermore, mutations of two conserved negatively charged residues of Tim23, close to the inner membrane, prevented dimerization of Tim23. The same mutations increased exposure of Tim23 on the mitochondrial surface, whereas dissipation of membrane potential decreased it. Our results reveal an intricate network of Tim23 interactions in the IMS, whose influence is transduced across two mitochondrial membranes, ensuring efficient translocation of proteins into mitochondria. (C) 2020 The Author(s). Published by Elsevier Ltd

    Understanding NF-ÎșB signaling via mathematical modeling

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    Mammalian inflammatory signaling, for which NF-ÎșB is a principal transcription factor, is an exquisite example of how cellular signaling pathways can be regulated to produce different yet specific responses to different inflammatory insults. Mathematical models, tightly linked to experiment, have been instrumental in unraveling the forms of regulation in NF-ÎșB signaling and their underlying molecular mechanisms. Our initial model of the IÎșB–NF-ÎșB signaling module highlighted the role of negative feedback in the control of NF-ÎșB temporal dynamics and gene expression. Subsequent studies sparked by this work have helped to characterize additional feedback loops, the input–output behavior of the module, crosstalk between multiple NF-ÎșB-activating pathways, and NF-ÎșB oscillations. We anticipate that computational techniques will enable further progress in the NF-ÎșB field, and the signal transduction field in general, and we discuss potential upcoming developments

    Efficacy and safety of P11-4 for the treatment of periodontal defects in dogs

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    Objectives: This study's aim was to investigate the safety and performance of a self-assembling peptide matrix (SAPM) P11-4 for the treatment of periodontal disease in a controlled pre-clinical study. Materials and methods: Acute buccal bony dehiscence defects (LxW: 5 × 3 mm) were surgically created on the distal root of four teeth on one mandible side of 7 beagle dogs followed by another identical surgery 8 weeks later on the contralateral side. SAPM P11-4 (with and without root conditioning with 24% EDTA (T1, T2)), EmdogainÂź (C) and a sham intervention (S) were randomly applied on the four defects at each time point. Four weeks after the second surgery and treatment, the animals were sacrificed, the mandibles measured by micro-computed tomography (”-CT) and sections of the tissue were stained and evaluated histologically. Results: Clinically and histologically, no safety concerns or pathological issues due to the treatments were observed in any of the study groups at any time point. All groups showed overall similar results after 4 and 12 weeks of healing regarding new cementum, functionality of newly formed periodontal ligament and recovery of height and volume of the new alveolar bone and mineral density. Conclusion: A controlled clinical study in humans should be performed in a next step as no adverse effects or safety issues, which might affect clinical usage of the product, were observed. Clinical relevance: The synthetic SAPM P11-4 may offer an alternative to the animal-derived product EmdogainÂź in the future

    Migraine in postmenopausal women and the risk of invasive breast cancer.

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    BACKGROUND: The frequency of migraine headache changes at various times of a woman's reproductive cycle. Menarche, menses, pregnancy, and perimenopause may carry a different migraine risk conceivably because of fluctuating estrogen levels, and in general, migraine frequency is associated with falling estrogen levels. Given the strong relationship between endogenous estrogen levels and breast cancer risk, migraine sufferers may experience a reduced risk of breast cancer. METHODS: We combined data from two population-based case-control studies to examine the relationship between migraine and risk of postmenopausal invasive breast cancer among 1,199 ductal carcinoma cases, 739 lobular carcinoma cases, and 1,474 controls 55 to 79 years of age. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Women who reported a clinical diagnosis of migraine had reduced risks of ductal carcinoma (OR, 0.67; 95% CI, 0.54-0.82) and lobular carcinoma (OR, 0.68; 95% CI, 0.52-0.90). These associations were primarily limited to hormone receptor-positive tumors as migraine was associated with a 0.65-fold (95% CI, 0.51-0.83) reduced risk of estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+) ductal carcinoma. The reductions in risk observed were seen among migraine sufferers who did and did not use prescription medications for their migraines. CONCLUSIONS: These data suggest that a history of migraine is associated with a decreased risk of breast cancer, particularly among ER+/PR+ ductal and lobular carcinomas. Because this is the first study to address an association between migraine history and breast cancer risk, additional studies are needed to confirm this finding

    Development and application of a 3D periodontal in vitro model for the evaluation of fibrillar biomaterials

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    Background: Periodontitis is a chronic inflammation of the tooth supporting structures that finally can lead to tooth loss. As chronic periodontitis is associated with systemic diseases multiple approaches have been followed to support regeneration of the destructed tissue. But very few materials are actually used in the clinic. A new and promising group of biomaterials with advantageous biomechanical properties that have the ability to support periodontal regeneration are self-assembling peptides (SAP). However, there is still a lack of 3D periodontal models that can evaluate the migration potential of such novel materials. Methods: All experiments were performed with primary human periodontal ligament fibroblasts (HPLF). Migration capacity was assessed in a three-dimensional model of the human periodontal ligament by measuring the migration distance of viable cells on coated (Enamel Matrix Protein (EMP), P11–4, collagen I) or uncoated human dentin. Cellular metabolic activity on P11–4 hydrogels was assessed by a metabolic activity assay. Deposition of ECM molecules in a P11–4 hydrogel was visualized by immunostaining of collagen I and III and fibrillin I. Results: The 3D periodontal model was feasible to show the positive effect of EMP for periodontal regeneration. Subsequently, self-assembling peptide P11–4 was used to evaluate its capacity to support regenerative processes in the 3D periodontal model. HPLF coverage of the dentin surface coated with P11–4 increased significantly over time, even though delayed compared to EMP. Cell viability increased and inclusion of ECM proteins into the biomaterial was shown. Conclusion: The presented results indicate that the 3D periodontal model is feasible to assess periodontal defect coverage and that P11–4 serves as an efficient supporter of regenerative processes in the periodontal ligament. Clinical relevance: The establishment of building-block synthetic polymers offers new opportunities for clinical application in dentistry. Self-assembling peptides represent a new generation of biomaterials as they are able to respond dynamically to the changing environment of the biological surrounding. Especially in the context of peri-implant disease prevention and treatment they enable the implementation of new concepts

    Multifunctional PLGA nanoparticles combining transferrin-targetability and pH-stimuli sensitivity enhanced doxorubicin intracellular delivery and in vitro antineoplastic activity in MDR tumor cells

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    Targeted delivery aims to enhance cellular uptake and improve therapeutic outcome with higher disease specificity. The expression of transferrin receptor (TfR) is upregulated on tumor cells, which make the protein Tf and its receptor vastly relevant when applied to targeting strategies. Here, we proposed Tf-decorated pH-sensitive PLGA nanoparticles containing the chemosensitizer poloxamer as a carrier for doxorubicin delivery to tumor cells (Tf-DOX-PLGA-NPs), aiming at alleviating multidrug resistance (MDR). We performed a range of in vitro studies to assess whether targeted NPs have the ability to improve DOX antitumor potential on resistant NCI/ADR-RES cells. All evaluations of the Tf-decorated NPs were performed comparatively to the nontargeted counterparts, aiming to evidence the real role of NP surface functionalization, along with the benefits of pH-sensitivity and poloxamer, in the improvement of antiproliferative activity and reversal of MDR. Tf-DOX-PLGA-NPs induced higher number of apoptotic events and ROS generation, along with cell cycle arrest. Moreover, they were efficiently internalized by NCI/ADR-RES cells, increasing DOX intracellular accumulation, which supports the greater cell killing ability of these targeted NPs with respect to MDR cells. Altogether, these findings supported the effectiveness of the Tf-surface modification of DOX-PLGA-NPs for an improved antiproliferative activity. Therefore, our pH-responsive Tf-inspired NPs are a promising smart drug delivery system to overcome MDR effect at some extent, enhancing the efficacy of DOX antitumor therapy
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