Liquid-immersion laser micromachining of GaN grown on sapphire

Liquid-immersion nanosecond-pulsed laser micromachining is introduced as an efficient way for device isolation and rapid prototyping on GaN-on-sapphire wafer. Using deionized water as an ambient medium for laser micromachining, smooth trenches that are free from redeposition can be formed in the GaN layer. Coupled with the large difference between the ablation thresholds and ultraviolet absorption coefficients of GaN and sapphire, the GaN/sapphire interface can be left undamaged after the ablation process. This technique overcomes the limitation of heat accumulation in nanosecond-pulse regime, and offers a cost-effective alternative to ultrashort-pulse laser micromachining. In this report, the advantages offered by liquid immersion are elucidated in terms of improved heat conduction, increased plasma-induced recoil pressure due to water confinement, weakened plasma shielding effect in water, and the collapse of cavitation bubbles. Simulation results show that the reduced fluctuation of temperature profile over time in water could be correlated with the reduced redeposition of Ga from thermal decomposition at the trench sidewalls. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 31 May 201

Interconnected alternating-current light-emitting diode arrays isolated by laser micromachining

The fabrication and operation of a monolithic InGaN alternating-current light-emitting diode (LED) based on the bridge rectifier design are demonstrated. The device consists of on-chip interconnected LED elements that have been isolated by direct-write laser micromachining, a powerful tool well-suited for rapid device prototyping. The effects of capacitors coupled to the dc path of the rectifier have been investigated. Although an increase of radiant flux can be achieved through capacitive voltage smoothening, the wall-plug efficiency drops as a result. The device can be applied to 12 Vrms lighting applications. © 2011 American Vacuum Society.published_or_final_versio

Enhanced powder dispersion of dual-excipient spray-dried powder formulations of a monoclonal antibody and its fragment for local treatment of severe asthma

The advent of biologics has brought renewed hope for patients with severe asthma, a condition notorious for being hampered by poor response to conventional therapies and adverse drug reactions owing to corticosteroid dependence. However, biologics are administered as injections, thereby precluding the benefits inhalation therapy could offer such as increased bioavailability at the site of action, minimal systemic side effects, non-invasiveness, and self-administration. Here, 2-hydroxypropyl-beta-cyclodextrin and ʟ-leucine were co-spray-dried, as protein stabiliser and dispersion enhancer, respectively, at various weight ratios to produce a series of formulation platforms. Powder aerosolisation characteristics and particle morphology were assessed for suitability for pulmonary delivery. The selected platform with the best aerosol performance, a 1:1 ratio of the excipients, was then incorporated with a monoclonal antibody directed against IL-4 receptor alpha or its antigen-binding fragment. The dual-excipient antibody formulations exhibited emitted fraction of at least 80% and fine particle fraction exceeding 60% in cascade impactor study, while the residual moisture content was within a desirable range between 1% and 3%. The in vitro antigen-binding ability and inhibitory potency of the spray-dried antibody were satisfactorily preserved. The results from this study corroborate the viability of inhaled solid-state biomacromolecules as a promising treatment approach for asthma

Lack of activated protein C resistance in healthy Hong Kong Chinese blood donors--correlation with absence of Arg506-Gln mutation of factor V gene.

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High incidence of thrombophilia detected in Chinese patients with venous thrombosis

Venous thromboembolism is rare in Chinese. To determine the incidence and disease profile of thrombophilia in Chinese patients with thrombosis, 52 unselected Chinese patients with documented venous thrombosis were studied for the presence of thrombophilia. Levels of antithrombin III (AT III), protein C (PC) and protein S (PS) as well as the presence of acquired lupus anticoagulant (LA) and anticardiolipin antibody (ACA) were investigated. Thirty patients were found to be abnormal. These consisted of 5 AT III deficiencies, 9 PC deficiencies, 10 PS deficiencies, 1 combined PC and PS deficiency (all in the heterozygous range), and 5 patients with LA and/or ACA. When the patients with LA and/or ACA are excluded, the incidence of hereditary thrombophilia is 25/47 i.e. 53.2% which is much higher than those reported in studies of Caucasian patients selected under strict criteria. Family studies performed in 16 cases of hereditary thrombophilia revealed involvement in 11 cases (68.7%); a total of 36 heterozygous family members were affected, most of which remain asymptomatic. Although 35 events predisposing to thrombosis (27 pregnancies, 1 oral contraceptive consumption and 7 surgical operations) were identified among these index patients, and the heterozygous family members, thrombosis was observed on only 6 occasions (17.1%). The data suggest that pregnancy and surgery do not carry the same degree of thrombotic risk in Chinese as in the Caucasian population with heterozygous AT III, PC and PS deficiency.published_or_final_versio

Storage stability of lysostaphin solution and its pulmonary delivery

Methicillin-resistant Staphylococcus aureus (MRSA) has become a leading causative pathogen of nosocomial pneumonia with an alarming in-hospital mortality rate of 30%. Last resort antibiotic, vancomycin, has been increasingly used to treat MRSA infections, but the rapid emergence of vancomycin-resistant strains urges the development of alternative treatment strategies against MRSA-associated pneumonia. The bacteriolytic enzyme, lysostaphin, targeting the cell wall peptidoglycan of S. aureus, has been considered as a promising alternative for MRSA infections. Its proteinaceous nature is likely benefit from direct delivery to the lungs, but the challenges for successful pulmonary delivery of lysostaphin lying on a suitable inhalation device and a formulation with sufficient storage stability. In this study, the applicability of a vibrating mesh nebulizer (Aerogen Solo®) and a soft mist inhaler (Respimat®) was investigated. Both devices were capable of aerosolizing lysostaphin solution into inhalable droplets and caused minimum antibacterial activity loss. In addition, lysostaphin stabilized with phosphate-buffered saline and 0.1% Tween 80 was proved to have acceptable stability for at least 12 months when stored at 4 °C. These promising data encourage further clinical development of lysostaphin for management of MRSA-associated lung infections. Graphical abstract: [Figure not available: see fulltext.] Lysostaphin had insignificant activity loss after aerosol generation by a vibrating mesh nebulizer and a soft mist inhaler.Most of the lysostaphin aerosols generated by the vibrating mesh nebulizer and soft mist inhaler are inhalable.The vibrating mesh nebulizer and soft mist inhaler are suitable device for pulmonary delivery of lysostaphin

Musculoskeletal strength, balance performance and self-efficacy in elderly Ving Tsun Chinese martial art practitioners: Implications for fall prevention

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Bilateral pheochromocytomas in MEN2A syndrome: a two-institution experience

postprin

Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation

Neutralising monoclonal antibody (mAb) is an important weapon in our arsenal for combating respiratory viral infections. However, the effectiveness of neutralising mAb has been impeded by the rapid emergence of mutant variants. Early administration of broad-spectrum mAb with improved delivery efficiency can potentially enhance efficacy and patient outcomes. WKS13 is a humanised mAb which was previously demonstrated to exhibit broad-spectrum activity against SARS-CoV-2 variants. In this study, a dual targeting formulation strategy was designed to deliver WKS13 to both the nasal cavity and lower airways, the two critical sites of infection caused by SARS-CoV-2. Dry powders of WKS13 were first prepared by spray drying, with cyclodextrin used as stabiliser excipient. Two-fluid nozzle (TFN) was used to produce particles below 5 μm for lung deposition (C-TFN formulation) and ultrasonic nozzle (USN) was used to produce particles above 10 μm for nasal deposition (C-USN formulation). Gel electrophoresis and size exclusion chromatography studies showed that the structural integrity of mAb was successfully preserved with no sign of aggregation after spray drying. To achieve dual targeting property, C-TFN and C-USN were mixed at various ratios. The aerosolisation property of the mixed formulations dispersed from a nasal powder device was examined using a Next Generation Impactor (NGI) coupled with a glass expansion chamber. When the ratio of C-TFN in the mixed formulation increased, the fraction of particles deposited in the lung increased proportionally while the fraction of particles deposited in the nasal cavity decreased correspondingly. A customisable aerosol deposition profile could therefore be achieved by manipulating the mixing ratio between C-TFN and C-USN. Dual administration of C-TFN and C-USN powders to the lung and nasal cavity of hamsters, respectively, was effective in offering prophylactic protection against SARS-CoV-2 Delta variant. Viral loads in both the lung tissues and nasal wash were significantly reduced, and the efficacy was comparable to systemic administration of unformulated WKS13. Overall, dual targeting powder formulation of neutralising mAb is a promising approach for prophylaxis of respiratory viral infections. The ease and non-invasive administration of dual targeting nasal powder may facilitate the widespread distribution of neutralising mAb during the early stage of unpredictable outbreaks

Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer

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