Identification of a Novel Genomic Island Conferring Resistance to Multiple Aminoglycoside Antibiotics in Campylobacter coli

Historically, the incidence of gentamicin resistance in Campylobacter has been very low, but recent studies reported a high prevalence of gentamicin-resistant Campylobacter isolated from food-producing animals in China. The reason for the high prevalence was unknown and was addressed in this study. PCR screening identified aminoglycoside resistance genes aphA-3 and aphA-7 and the aadE–sat4–aphA-3 cluster among 41 Campylobacter isolates from broiler chickens. Importantly, a novel genomic island carrying multiple aminoglycoside resistance genes was identified in 26 aminoglycoside resistant Campylobacter coli strains. Sequence analysis revealed that the genomic island was inserted between cadF and COO1582 on the C. coli chromosome and consists of 14 open reading frames (ORFs), including 6 genes (the aadE–sat4–aphA-3 cluster, aacA-aphD, aac, and aadE) encoding aminoglycoside-modifying enzymes. Analysis by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing indicated that the C. coli isolates carrying this unique genomic island were clonal, and the clone of PFGE subtype III and sequence type (ST) 1625 was particularly predominant among the C. coli isolates examined, suggesting that clonal expansion may be involved in dissemination of this resistance island. Additionally, we were able to transfer this genomic island from C. coli to a Campylobacter jejuni strain using natural transformation under laboratory conditions, and the transfer resulted in a drastic increase in aminoglycoside resistance in the recipient strain. These findings identify a previously undescribed genomic island that confers resistance to multiple aminoglycoside antibiotics. Since aminoglycoside antibiotics are used for treating occasional systemic infections caused by Campylobacter, the emergence and spread of this antibiotic resistance genomic island represent a potential concern for public health

Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200–400 kPa, 4–5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4–20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of’ visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4–5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used

Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

Abstract Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200-400 kPa, 4-5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemicallyadministered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used

Long-lived and disorder-free charge transfer states enable endothermic charge separation in efficient non-fullerene organic solar cells

Funder: HKU | University Research Committee, University of Hong Kong (HKU Research Committee); doi: https://doi.org/10.13039/501100003802Abstract: Organic solar cells based on non-fullerene acceptors can show high charge generation yields despite near-zero donor–acceptor energy offsets to drive charge separation and overcome the mutual Coulomb attraction between electron and hole. Here, we use time-resolved optical spectroscopy to show that free charges in these systems are generated by thermally activated dissociation of interfacial charge-transfer states that occurs over hundreds of picoseconds at room temperature, three orders of magnitude slower than comparable fullerene-based systems. Upon free electron–hole encounters at later times, both charge-transfer states and emissive excitons are regenerated, thus setting up an equilibrium between excitons, charge-transfer states and free charges. Our results suggest that the formation of long-lived and disorder-free charge-transfer states in these systems enables them to operate closely to quasi-thermodynamic conditions with no requirement for energy offsets to drive interfacial charge separation and achieve suppressed non-radiative recombination

Mulberry Leaf Regulates Differentially Expressed Genes in Diabetic Mice Liver Based on RNA-Seq Analysis

The pathogenesis of diabetes mellitus is a complicated process involving much gene regulation. The molecular mechanism of mulberry (Morus alba L.) leaf in the treatment of diabetes is not fully understood. In this study, we used the Illumina HiSeq™ 2,500 platform to explore the liver transcriptome of normal mice, STZ-induced diabetic mice, and mulberry leaf-treated diabetic mice, and we obtained 52,542,956, 52,626,414, and 52,780,196 clean reads, respectively. We identified differentially expressed genes (DEGs) during the pathogenesis of diabetes in mice. The functional properties of DEGs were characterized by comparison with the GO and KEGG databases, and the results show that DEGs are mainly involved in the metabolic pathway. qRT-PCR was used to analyse 27 differential genes involved in liver expression in different groups of diabetic mice. Among the DEGs, the expression of Scube1, Spns3, Ly6a, Igf2, and other genes between the control (C) and diabetic control (DC) groups was significantly upregulated; the expression of Grb10, Mup2, and Fasn was significantly downregulated; the expression of the Sqle, Lss, and Irs2 genes between the C group and diabetic group treated with mulberry (DD) was significantly upregulated; the expression of Fabp2, Ly6a, and Grb10 was significantly downregulated; and the expression of Sqle and Lss was significantly upregulated in the DC and DD groups, but Tap1, Igf2, and Spns3 were significantly downregulated. The results of Western blot validation showed that dynamic changes in proteins, such as IGF2, Ly6a, Grb10, and UBD, occurred to regulate the incidence of diabetes by influencing the insulin receptor substrate (IRS) signaling pathway

Impact investing in the era of collaborative governance : an empirical study on four cases in Hong Kong

Impact investing, a new form of investment intended to create positive social and environmental impacts beyond financial returns, has prevailed around the globe. As a hybrid concept, impact investing embodies social responsibility and financial sustainability, and its development has been a collaborative effort engaging players from the public, private and third sectors. Such an unprecedented convergence of tri-sector stakeholders has also brought about new challenges. Despite the proliferation of research reports of impact investing in the practitioners’ field, little systematic study has been devoted to understanding the intractability of effective collaboration and its policy perspective in this cross-sector arena. Hong Kong has also been enthusiastic about impact investing, however, not all of the momentum has translated into concrete actions. Local players are still trapped in their own silos with limited investing activities, and “cross-sector collaboration”remains a black box. An empirical inquiry into the collaborative issues in Hong Kong’s local context is long overdue. Given the launch of the Social Innovation and Entrepreneurship Fund by the Hong Kong SAR, the policy implications of impact investing and the role of government can be explored using concrete examples. To address the challenge confronting collaboration, this study seeks answers to three research questions. First, what factors influence impact investors to collaborate with other stakeholders? Second, how are the collaborative dynamics shaped to induce impact-investing activities? Third, what effect does government intervention have on this collaboration? The research design is framed by the collaborative governance model, rested on the theoretical foundation of collective action. As an exploratory study, the literature review draws upon a board set of extant frameworks and propositions to generate observable implications such as resource dependency theory and power dynamics to understand the motives, means and barriers in collaboration. It is a multi-phased qualitative case study on four impact investors in Hong Kong through analysis of documents, interviews and observations. Process-tracing and multiple narratives are employed to further develop two embedded cases of collaborative projects. The cross-case comparison reveals how starting conditions and collaboration process affect different types of impact investors/venture philanthropists, with both commonalities and variations in the generic rationale of stakeholder engagement and specific consideration on typical investment. The paradoxes of embeddedness vs publicness, and institutionalization vs joint discretion are discussed. Recommendations are made on the respective roles backbone organization and government could play to best use impact investing in the era of collaborative governance for a better society.published_or_final_versionPolitics and Public AdministrationMasterMaster of Philosoph

Ligand assisted growth of perovskite single crystals with low defect density

A low defect density in metal halide perovskite single crystals is critical to achieve high performance optoelectronic devices. Here we show the reduction of defect density in per[1]ovskite single crystals grown by a ligand-assisted solution process with 3‐(decyldimethy[1]lammonio)‐propane‐sulfonate inner salt (DPSI) as an additive. DPSI ligands anchoring with lead ions on perovskite crystal surfaces not only suppress nucleation in solution, but also regulate the addition of proper ions to the growing surface, which greatly enhances the crystal quality. The grown CH3NH3PbI3 crystals show better crystallinity and a 23-fold smaller trap density of 7 × 1010 cm−3 than the optimized control crystals. The enhanced material properties result in significantly suppressed ion migration and superior X-ray detection sensitivity of CH3NH3PbI3 detectors of (2.6 ± 0.4) × 106 µC Gy−1 air cm−2 for 60 kVp X-ray and the lowest detectable dose rate reaches (5.0 ± 0.7) nGy s−1 , which enables reduced radiation dose to patients in medical X-ray diagnostics

Influence of anchor uncertainty on the failure probability of reinforced slope

To explore the influence of anchor uncertainty on the failure probability of reinforced slopes, the uncertainty of anchors is considered through the following two approaches: one assumes that the friction force on the unit surface of the contact surface between the anchor and the anchor solid is a log-normal distribution variable, and the other introduces the attenuation coefficient of the friction force on the unit surfaceof the contact surface between the anchor and the anchor solid to consider the uncertainty of the anchor during construction and maintenance. The limit equilibrium method and Monte Carlo sampling method are used to calculate and compare the variation curve of the failure probability of the reinforced slope through two approaches.Finally, the effectiveness of the proposed method is validated against an example of the slope retaining project of the Shenzhen Holiday Inn foundation pit.The results show that the failure probability of the reinforced slope increases gradually with the increase range in the coefficient of variation of unit surface friction on the contact surface between the anchor and the anchor solid under the same soil statistical parameters, and the increase range is between 18.03% and 41.90% for the first approach. For the second approach, the failure probability of the reinforced slope increases rapidly with the decrease in the attenuation coefficient of the anchor ranging from 1.0 to 0.0, and the increase range is between 55.64% and 124.90%. Under the same attenuation coefficient, the failure probability of the reinforced slope increases with the increase in the number of attenuation anchors. The research results provide decision support for the management of anchors during construction and operation

Cs(I) Cation Enhanced Cu(II) Catalysis of Water Oxidation

We report here a new catalytic water oxidation system based on Cu­(II) ions and a remarkable countercation effect on the catalysis. In a concentrated fluoride solution at neutral to weakly basic pHs, simple Cu­(II) salts are highly active and robust in catalyzing water oxidation homogeneously. F^– in solution acts as a proton acceptor and an oxidatively robust ligand. F^– coordination prevents precipitation of Cu­(II) as CuF₂/Cu­(OH)₂ and lowers potentials for accessing high-oxidation-state Cu by delocalizing the oxidative charge over F^– ligands. Significantly, the catalytic current is greatly enhanced in a solution of CsF compared to those of KF and NaF. Although countercations are not directly involved in the catalytic redox cycle, UV–vis and ¹⁹F nuclear magnetic resonance measurements reveal that coordination of F^– to Cu­(II) is dependent on countercations by Coulombic interaction. A less intense interaction between F^– and well-solvated Cs⁺ as compared with Na⁺ and K⁺ leads to a more intense coordination of F^– to Cu­(II), which accounts for the improved catalytic performance

Preparation of a new polymeric ionic liquid-based monolith for stir cake sorptive extraction and its application in the extraction of inorganic anions

In this study, a novel stir cake sorptive extraction (SCSE) sorbent based on polymeric ionic liquid-based monolith (PILM) for the extraction of inorganic anions was prepared. In the presence of a porogen solvent containing 1-propanol and dimethylformamid, an ionic liquid, 1-ally-3-methylimidazolium chloride was used as monomer to copolymerize in situ with ethylene dimethacrylate to form PILM. The effect of preparation conditions such as ratio of functional monomer to cross-linker, content of porogenic solvent on the extraction efficiencies were investigated in detail. The PILM was characterized by elemental analysis, scanning electron microscopy, mercury intrusion porosimetry and infrared spectroscopy. In order to investigate the extraction capacity of PILM-SCSE for inorganic anions, the SCSE was combined with ion chromatography with conductivity detection, F-, Cl-, NO2-, Br-, NO3-, PO43- and SO42- were selected as detected solutes. Several extractive parameters, including pH values in sample matrix, desorption solvent, extraction and desorption time were optimized. The results showed that under the optimum experimental conditions, low detection limits (S/N = 3) and quantification limits (S/N= 10) of the proposed method for the target anions were achieved within the range of 0.11-2.08 and 0.37-6.88 mu g/L, respectively. The method also showed good linearity, simplicity, practicality and low cost for the extraction inorganic anions. Finally, the proposed method was successfully used to detect different water samples include commercial purified water, tab water and river water. Acceptable recoveries and satisfactory repeatability were obtained. To the best of our knowledge, this is the first to use polymeric ionic liquid to enrich inorganic anions. (c) 2012 Elsevier B.V. All rights reserved.National Natural Science Foundation of China [21077085]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry; New Century Excellent Talents in Fujian Province University; Fundamental Research Funds for the Central Universities [CXB2011037