1,139 research outputs found
Gate-controllable spin-battery
We propose a gate-controllable spin-battery for spin current. The
spin-battery consists of a lateral double quantum dot under a uniform magnetic
field. A finite DC spin-current is driven out of the device by controlling a
set of gate voltages. Spin-current can also be delivered in the absence of
charge-current. The proposed device should be realizable using present
technology at low temperature.Comment: 3 pages, 3 figures, accepted by Appl. Phys. Let
Pharmacokinetic/Pharmacodynamic Correlation of Cefquinome Against Experimental Catheter-Associated Biofilm Infection Due to Staphylococcus aureus.
Biofilm formations play an important role in Staphylococcus aureus pathogenesis and contribute to antibiotic treatment failures in biofilm-associated infections. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of cefquinome against an experimental catheter-related biofilm model due to S. aureus, including three clinical isolates and one non-clinical isolate. The minimal inhibitory concentration (MIC), minimal biofilm inhibitory concentration (MBIC), biofilm bactericidal concentration (BBC), minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) and in vitro time-kill curves of cefquinome were studied in both planktonic and biofilm cells of study S. aureus strains. The in vivo post-antibiotic effects (PAEs), PK profiles and efficacy of cefquinome were performed in the catheter-related biofilm infection model in murine. A sigmoid E max model was utilized to determine the PK/PD index that best described the dose-response profiles in the model. The MICs and MBICs of cefquinome for the four S. aureus strains were 0.5 and 16 μg/mL, respectively. The BBCs (32-64 μg/mL) and MBECs (64-256 μg/mL) of these study strains were much higher than their corresponding BPC values (1-2 μg/mL). Cefquinome showed time-dependent killing both on planktonic and biofilm cells, but produced much shorter PAEs in biofilm infections. The best-correlated PK/PD parameters of cefquinome for planktonic and biofilm cells were the duration of time that the free drug level exceeded the MIC (fT > MIC, R (2) = 96.2%) and the MBIC (fT > MBIC, R (2) = 94.7%), respectively. In addition, the AUC24h/MBIC of cefquinome also significantly correlated with the anti-biofilm outcome in this model (R (2) = 93.1%). The values of AUC24h/MBIC for biofilm-static and 1-log10-unit biofilm-cidal activity were 22.8 and 35.6 h; respectively. These results indicate that the PK/PD profiles of cefquinome could be used as valuable guidance for effective dosing regimens treating S. aureus biofilm-related infections
Recommended from our members
Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection.
Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P < 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA
Phenotypic Characterization of Osteoarthritic Osteocytes from the Sclerotic Zones: A Possible Pathological Role in Subchondral Bone Sclerosis
Subchondral bone sclerosis is a well-recognised manifestation of osteoarthritis (OA). The osteocyte cell network is now considered to be central to the regulation of bone homeostasis; however, it is not known whether the integrity of the osteocyte cell network is altered in OA patients. The aim of this study was to investigate OA osteocyte phenotypic changes and its potential role in OA subchondral bone pathogenesis. The morphological and phenotypic changes of osteocytes in OA samples were investigated by micro-CT, SEM, histology, immunohistochemistry, TRAP staining, apoptosis assay and real-time PCR studies. We demonstrated that in OA subchondral bone, the osteocyte morphology was altered showing rough and rounded cell body with fewer and disorganized dendrites compared with the osteocytes in control samples. OA osteocyte also showed dysregulated expression of osteocyte markers, apoptosis, and degradative enzymes, indicating that the phenotypical changes in OA osteocytes were accompanied with OA subchondral bone remodelling (increased osteoblast and osteoclast activity) and increased bone volume with altered mineral content. Significant alteration of osteocytes identified in OA samples indicates a potential regulatory role of osteocytes in subchondral bone remodelling and mineral metabolism during OA pathogenesis
Fe-based high temperature superconductivity with Tc=31K bordering an insulating antiferromagnet in (Tl,K)FexSe2 Crystals
Up to now, there have been two material families, the cuprates and the
iron-based compounds with high-temperature superconductivity (HTSC). An
essential open question is whether the two classes of materials share the same
essential physics. In both, superconductivity (SC) emerges when an
antiferromagnetical (AFM) ordered phase is suppressed. However, in cuprates,
the repulsive interaction among the electrons is so strong that the parent
compounds are "Mott insulators." By contrast, all iron-based parents are
metallic. One perspective is that the iron-based parents are weakly correlated
and that the AFM arises from a strong "nesting" of the Fermi surfaces. An
alternative view is that the electronic correlations in the parents are still
sufficiently strong to place the system close to the boundary between
itinerancy and electronic localization. A key strategy to differentiate theses
views is to explore whether the iron-based system can be tuned into a Mott
insulator. Here we identify an insulating AFM in (Tl,K)FexSe2 by introducing
Fe-vacancies and creating superconductivity in the Fe-planar. With the
increasing Fe-content, the AFM order is reduced. When the magnetism is
eliminated, a superconducting phase with Tc as high as 31K (and a Tc onset as
high as 40K) is induced. Our findings indicate that the correlation effect
plays a crucial role in the iron-based superconductors. (Tl,K)FexSe2,
therefore, represents the first Fe-based high temperature superconductor near
an insulating AFM.Comment: 20 pages, 8 figure
The biological function of type I receptors of bone morphogenetic protein in bone
Bone morphogenetic proteins (BMPs) have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors (BMPRI and BMPRII). In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 (ALK2, also called type IA activin receptor), activin-like kinase 3 (ALK3, also called BMPRIA), and activin-like kinase 6 (ALK6, also called BMPRIB). The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future
Recommended from our members
Identification of domestication-related loci associated with flowering time and seed size in soybean with the RAD-seq genotyping method
Flowering time and seed size are traits related to domestication. However, identification of domestication-related loci/genes of controlling the traits in soybean is rarely reported. In this study, we identified a total of 48 domestication-related loci based on RAD-seq genotyping of a natural population comprising 286 accessions. Among these, four on chromosome 12 and additional two on chromosomes 11 and 15 were associated with flowering time, and four on chromosomes 11 and 16 were associated with seed size. Of the five genes associated with flowering time and the three genes associated with seed size, three genes Glyma11g18720, Glyma11g15480 and Glyma15g35080 were homologous to Arabidopsis genes, additional five genes were found for the first time to be associated with these two traits. Glyma11g18720 and Glyma05g28130 were co-expressed with five genes homologous to flowering time genes in Arabidopsis, and Glyma11g15480 was co-expressed with 24 genes homologous to seed development genes in Arabidopsis. This study indicates that integration of population divergence analysis, genome-wide association study and expression analysis is an efficient approach to identify candidate domestication-related genes
- …