Effect of mandibular and tongue protrusion on upper airway size during wakefulness

Oral appliances for the treatment of obstructive sleep apnea (OSA) produce either mandibular or tongue protrusion, and are thought to enlarge the upper airway (UA). We used videoendoscopy to measure UA cross-sectional area (CSA) and shape in the hypopharynx, oropharynx, and velopharynx during various stages of active mandibular and tongue protrusion during wakefulness in 10 patients with OSA and nine control subjects. Measurements were made in the supine position at end-tidal expiration, and were normalized to the CSA in the normal bite position. Airway shape was expressed as the anteroposterior/lateral (AP/L) diameter ratio. There were no differences between OSA patients and controls in the effects of mandibular and tongue protrusion on UA caliber. Both mandibular and tongue protrusion increased CSA in the hypopharynx and oropharynx (p < 0.001), whereas only tongue protrusion increased CSA in the velopharynx (p < 0.001). Tongue protrusion caused a greater increase in oropharyngeal and velopharyngeal CSA than did mandibular protrusion (p < 0.05). Mandibular protrusion caused a greater increase in CSA in the hypopharynx than in the oropharynx or velopharynx (p < 0.05). Obese patients had a larger relative increase in oropharyngeal CSA with mandibular and tongue protrusion than did subjects of normal weight. Tongue protrusion increased the AP/L diameter ratio in the oropharynx and velopharynx (p < 0.001), and mandibular protrusion did so to a lesser extent in the oropharynx (p < 0.01), resulting in a more circular airway shape. We conclude that mandibular and tongue protrusion increase the CSA and alter the shape of the UA during wakefulness.     

Disruption of syntaxin-mediated protein interactions blocks neurotransmitter secretion

The membrane protein syntaxin participates in several protein-protein interactions that have been implicated in neurotransmitter release. To probe the physiological importance of these interactions, we microinjected into the squid giant presynaptic terminal botulinum toxin C1, which cleaves syntaxin, and the H3 domain of syntaxin, which mediates binding to other proteins. Both reagents inhibited synaptic transmission yet did not affect the number or distribution of synaptic vesicles at the presynaptic active zone. Recombinant H3 domain inhibited the interactions between syntaxin and SNAP-25 that underlie the formation of stable SNARE complexes in vitro. These data support the notion that syntaxin-mediated SNARE complexes are necessary for docked synaptic vesicles to fuse.     

基于离差最大化与灰关联耦合的空调冷热源优选模型

本文针对在进行空调系统冷热源方案优选时存在复杂性、模糊性和不确定性的问题,提出了一种基于离差最大化与灰色关联耦合的空调冷热源优选模型。模型依据方案在评价指标下各属性值之间的差异进行客观赋权,根据各方案与理想中最佳方案之间的关联度大小进行方案优选决策。通过在某工程项目空调冷热源优选中的应用,表明其计算简单、结果令人满意。     

APIC position paper: hepatitis C exposure in the health care setting. Association for Professionals in Infection Control and Epidemiology, Inc

The Association for Professionals in Infection Control and Epidemiology, Inc (APIC), is a multidisciplinary, voluntary, international organization of professionals who practice infection control and the application of epidemiology in all health settings. APIC is an international leader in prevention and control of infection transmission.     

Specificity of the SH2 domains of SHP-1 in the interaction with the immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B

Inhibitory receptors on hemopoietic cells critically regulate cellular function. Despite their expression on a variety of cell types, these inhibitory receptors signal through a common mechanism involving tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM), which engages Src homology 2 (SH2) domain-containing cytoplasmic tyrosine or inositol phosphatases. In this study, we have investigated the proximal signal-transduction pathway of an ITIM-bearing receptor, gp49B, a member of a newly described family of murine NK and mast cell receptors. We demonstrate that the tyrosine residues within the ITIMs are phosphorylated and serve for the association and activation of the cytoplasmic tyrosine phosphatase SHP-1. Furthermore, we demonstrate a physiologic association between gp49B and SHP-1 by coimmunoprecipitation studies from NK cells. To address the mechanism of binding between gp49B and SHP-1, binding studies involving glutathione S-transferase SHP-1 mutants were performed. Utilizing the tandem SH2 domains of SHP-1, we show that either SH2 domain can interact with phosphorylated gp49B. Full-length SHP-1, with an inactivated amino SH2 domain, also retained gp49B binding. However, binding to gp49B was disrupted by inactivation of the carboxyl SH2 domain of full-length SHP-1, suggesting that in the presence of the phosphatase domain, the carboxyl SH2 domain is required for the recruitment of phosphorylated gp49B. Thus, gp49B signaling involves SHP-1, and this association is dependent on tyrosine phosphorylation of the gp49B ITIMs, and an intact SHP-1 carboxyl SH2 domain.     

A dynamical investigation of acrylodan-labeled mutant phosphate binding protein

The static and dynamical behavior of a fluorescently labeled mutant of the Escherichia coli periplasmic phosphate binding protein (PBP) was investigated through steady-state and time-resolved fluorescence spectroscopy. As a means of developing a biorecognition element for inorganic phosphate (P(i)), alanine-197 of PBP was replaced with a cysteine. This site was then labeled with an environmentally sensitive fluorophore. The fluorescence emission of the mutant PBP labeled with acrylodan (MPBP-AC) proved to be sensitive to micromolar concentrations of P(i), as indicated by a 50% increase in the steady-state emission intensity. Steady-state results indicated that the labeling protocol was specific for cys-197 only and did not label the wild-type PBP; thus, a site-selective labeling protocol was developed. Time-resolved measurements were used to determine the influence of the dynamics of MPBP-AC on the process of signal transduction. Time-resolved anisotropy measurements revealed that rotational dynamics were best described by a model with two independent motions: the global motion of the protein and the local motion of the acrylodan probe. The rates of both global and local rotational reorientation of MPBP-AC were faster when the protein was P(i)-bound rather than P(i)-free. This was a result of structural changes involving or surrounding both the P(i)-binding site (global changes) and the residues in near proximity to the fluorescent reporter group (local changes). Recovery of the semiangle (theta) indicated that local structural changes in MPBP-AC took place when P(i) was bound to the protein. Acrylodan gained mobility when MPBP-AC bound P(i), as indicated by the fact that theta increased by approximately 5 degrees. In addition, dynamic quenching measurements confirmed that structural changes occurred locally near the cys-197. Acrylodan became more accessible to iodide when MPBP-AC bound P(i), as demonstrated by the 35% increase in the value of the bimolecular quenching constant.