819 research outputs found

    Iron oxide doped boron nitride nanotubes: structural and magnetic properties

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    A first-principles formalism is employed to investigate the interaction of iron oxide (FeO) with a boron nitride (BN) nanotube. The stable structure of the FeO-nanotube has Fe atoms binding N atoms, with bond length of roughly \sim2.1 \AA, and binding between O and B atoms, with bond length of 1.55 \AA. In case of small FeO concentrations, the total magnetic moment is (4μBohr\mu_{Bohr}) times the number of Fe atoms in the unit cell and it is energetically favorable to FeO units to aggregate rather than randomly bind to the tube. As a larger FeO concentration case, we study a BN nanotube fully covered by a single layer of FeO. We found that such a structure has square FeO lattice with Fe-O bond length of 2.11 \AA, similar to that of FeO bulk, and total magnetic moment of 3.94μBohr\mu_{Bohr} per Fe atom. Consistently with experimental results, the FeO covered nanotube is a semi-half-metal which can become a half-metal if a small change in the Fermi level is induced. Such a structure may be important in the spintronics context.Comment: 10 pages, 3 figure

    Results of reoperation on the upper esophageal sphincter

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    AbstractObjective: Reoperation on the upper esophageal sphincter is infrequent. We reviewed our experience in patients who underwent reoperation on the upper esophageal sphincter. Methods: This is a retrospective report of accumulative series from 2 separate institutions. Results: From September 1, 1976, to February 28, 1997, 37 patients underwent reoperation on the upper esophageal sphincter for recurrent or persistent obstructive symptoms. There were 29 men and 8 women. The median age was 69 years (range, 38-87 years). The original indication for the operation was a pharyngoesophageal (Zenker's) diverticulum in 33 patients (89.2%), oculopharyngeal dystrophy in 3 patients (8.1%), and muscular dystrophy in 1 patient (2.7%). One prior upper esophageal sphincter operation had been performed in 26 patients (70.3%), two operations in 9 patients (24.3%), and three operations in 2 patients (5.4%). All patients were symptomatic; 35 patients (94.6%) had dysphagia; 23 patients (62.2%) had regurgitation; and 12 patients (32.4%) had episodes of aspiration. Thirty of the patients (91.0%) with Zenker's diverticulum were found to have a recurrent or persistent diverticulum at reoperation. A diverticulectomy and cricopharyngeal myotomy were performed in 23 patients (62.2%); cricopharyngeal myotomy alone, in 7 patients (18.9%); diverticulopexy and cricopharyngeal myotomy, in 6 patients (16.2%); and diverticulectomy alone, in 1 patient (2.7%). There were no operative deaths. Complications developed in 10 patients (27.0%). Follow-up was complete in 34 patients (91.9%) and ranged from 2 to 149 months (median, 39 mo). Thirty-two patients (94.1%) were improved. Functional results were classified as excellent in 26 patients (76.5%), good in 2 patients (5.9%), fair in 4 patients (11.7%), and poor in 2 patients (5.9%). Conclusions: Reoperation for patients who have persistent or recurrent symptoms after an operation on the upper esophageal sphincter is associated with acceptable morbidity and mortality rates. Resolution of symptoms occurs in most patients. (J Thorac Cardiovasc Surg 1999;117:28-31

    Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK-LKB1 Signaling Axis.

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    Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 may couple cell proliferation to energy homeostasis

    3D Printed PLA Scaffolds to Promote Healing of Large Bone Defects

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    One challenge modern medicine faces is the ability to repair large bone defects and stimulate healing. Small defects typically heal naturally, but large bone defects do not and current solutions are to replace the missing tissue with biologically inert materials such as titanium. This limits the amount of bone healing as the defect is not repaired but rather replaced. The focus of our research is to develop a method of using 3D printing to create biodegradable scaffolds which promote bone in-growth and replacement. To accomplish this we used poly lactic acid (PLA) filament and a desktop 3D printer. To promote bone healing and provide mechanical support our team investigated different design methodologies to provide a scaffold of customizable stiffness while allowing cell attachment and in-growth. Our team used CAD modeling to create unique architecture design systems which we analyzed for stiffness using Finite Element Analysis (FEA). We developed a unit cell method of scaffold construction that allowed for customized stiffness of irregular shapes. We 3D printed our designs using a desktop 3D printer and verified our stiffness through mechanical tension and compression testing. We investigated cell viability of the scaffolds by immersing test specimens in culturing media and fibroblast cells. Fibroblast cells are from the same lineage as osteoblast cells but are much faster growing, allowing for more efficient testing. Specimens were left in the media for one week then a total cell count was performed. Scaffold designs were then evaluated based on stiffness and cell viability. We have produced several different viable models with appropriate stiffness for human trabecular bone and good cellular adhesion

    Discovery, Characterization, and Structure–Activity Relationships of an Inhibitor of Inward Rectifier Potassium (Kir) Channels with Preference for Kir2.3, Kir3.X, and Kir7.1

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    The inward rectifier family of potassium (Kir) channels is comprised of at least 16 family members exhibiting broad and often overlapping cellular, tissue, or organ distributions. The discovery of disease-causing mutations in humans and experiments on knockout mice has underscored the importance of Kir channels in physiology and in some cases raised questions about their potential as drug targets. However, the paucity of potent and selective small-molecule modulators targeting specific family members has with few exceptions mired efforts to understand their physiology and assess their therapeutic potential. A growing body of evidence suggests that G protein-coupled inward rectifier K (GIRK) channels of the Kir3.X subfamily may represent novel targets for the treatment of atrial fibrillation. In an effort to expand the molecular pharmacology of GIRK, we performed a thallium (Tl+) flux-based high-throughput screen of a Kir1.1 inhibitor library for modulators of GIRK. One compound, termed VU573, exhibited 10-fold selectivity for GIRK over Kir1.1 (IC50 = 1.9 and 19 μM, respectively) and was therefore selected for further study. In electrophysiological experiments performed on Xenopus laevis oocytes and mammalian cells, VU573 inhibited Kir3.1/3.2 (neuronal GIRK) and Kir3.1/3.4 (cardiac GIRK) channels with equal potency and preferentially inhibited GIRK, Kir2.3, and Kir7.1 over Kir1.1 and Kir2.1.Tl+ flux assays were established for Kir2.3 and the M125R pore mutant of Kir7.1 to support medicinal chemistry efforts to develop more potent and selective analogs for these channels. The structure–activity relationships of VU573 revealed few analogs with improved potency, however two compounds retained most of their activity toward GIRK and Kir2.3 and lost activity toward Kir7.1. We anticipate that the VU573 series will be useful for exploring the physiology and structure–function relationships of these Kir channels

    H3K36 Methylation Promotes Longevity by Enhancing Transcriptional Fidelity

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    Epigenetic mechanisms, including histone post-translational modifications, control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging phenomenon of shortened life span, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a life span screen in Saccharomyces cerevisiae that is designed to identify amino acid residues of histones that regulate yeast replicative aging. Our results reveal that lack of sustained histone H3K36 methylation is commensurate with increased cryptic transcription in a subset of genes in old cells and with shorter life span. In contrast, deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes, suppresses cryptic transcript initiation, and extends life span. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to loss of transcriptional precision that is detrimental to life span, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity

    Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort

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    Background β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (Type I) reactions mediated by antigen-specific IgE. Objective To identify genetic predisposing factors for immediate reactions to β-lactam antibiotics. Methods Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study (GWAS) was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort. Results GWAS identified rs71542416 within the Class II HLA region as the top hit (P = 2x10-14); this was in linkage disequilibrium with HLA-DRB1*10:01 (OR = 2.93 P = 5.4x10-7) and HLA-DQA1*01:05 (OR=2.93, P=5.4x10-7). Haplotype analysis identified that HLA-DRB1*10:01 was a risk factor even without the HLA-DQA1*01:05 allele. The association with HLA-DRB1*10:01 was replicated in another cohort, with the meta-analysis of the discovery and replication cohorts showing that HLA-DRB1*10:01 increased the risk of immediate hypersensitivity at a genome-wide level (OR = 2.96 P=4.1x10-9). No association with HLA-DRB1*10:01 was identified in 268 patients with delayed hypersensitivity reactions to β-lactams. Conclusion HLA-DRB1*10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required. Clinical implications This novel insight into the mechanisms of immediate reactions associated with penicillins may be of use in risk stratifying patients where penicillin cannot be excluded as an etiological agent

    The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial

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    Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/Vurea, a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome

    Testing Laser-Structured Antimicrobial Surfaces Under Space Conditions: The Design of the ISS Experiment BIOFILMS

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    Maintaining crew health and safety are essential goals for long-term human missions to space. Attaining these goals requires the development of methods and materials for sustaining the crew’s health and safety. Paramount is microbiological monitoring and contamination reduction. Microbial biofilms are of special concern, because they can cause damage to spaceflight equipment and are difficult to eliminate due to their increased resistance to antibiotics and disinfectants. The introduction of antimicrobial surfaces for medical, pharmaceutical and industrial purposes has shown a unique potential for reducing and preventing biofilm formation. This article describes the development process of ESA’s BIOFILMS experiment, that will evaluate biofilm formation on various antimicrobial surfaces under spaceflight conditions. These surfaces will be composed of different metals with and without specified surface texture modifications. Staphylococcus capitis subsp. capitis, Cupriavidus metallidurans and Acinetobacter radioresistens are biofilm forming organisms that have been chosen as model organisms. The BIOFILMS experiment will study the biofilm formation potential of these organisms in microgravity on the International Space Station on inert surfaces (stainless steel AISI 304) as well as antimicrobial active copper (Cu) based metals that have undergone specific surface modification by Ultrashort Pulsed Direct Laser Interference Patterning (USP-DLIP). Data collected in 1 x g has shown that these surface modifications enhance the antimicrobial activity of Cu based metals. In the scope of this, the interaction between the surfaces and bacteria, which is highly determined by topography and surface chemistry, will be investigated. The data generated will be indispensable for the future selection of antimicrobial materials in support of human- and robotic-associated activities in space exploration
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