High-efficiency small-molecule-based organic light emitting devices with solution processes and oxadiazole-based electron transport materials.

We demonstrate high-efficiency small-molecule-based white phosphorescent organic light emitting diodes (PHOLEDs) by single-active-layer solution-based processes with the current efficiency of 17.3 cdA(-1) and maximum luminous efficiency of 8.86 lmW(-1) at a current density of 1 mA cm(-2). The small-molecule based emitting layers are codoped with blue and orange phosphorescent dyes. We show that the presence of CsF/Al at cathodes not only improves electron transport in oxadiazole-containing electron transport layers (ETLs), but also facilitates electron injection through the reacted oxadiazole moiety to reduce interface resistance, which results in the enhancement of current efficiency. By selecting oxadiazole-based materials as ETLs with proper electron injection layer (EIL)/cathode structures, the brightness and efficiency of white PHOLEDs are significantly improved.

The effect on improvement of recovery and pain scores of paravertebral block immediately before breast surgery.

OBJECTIVES: Paravertebral block (PVB) has the potential to reduce postoperative pain after breast surgery. The aim of the study was to investigate whether PVB performed immediately before surgery could affect the postoperative morbidities in terms of pain and emesis, and improve the quality of recovery (QoR) in patients after surgery for breast cancer. METHODS: Postoperative data were collected prospectively from two groups of patients undergoing unilateral breast surgery during the study period of 1 month. Forty consecutive patients received either solely general anesthesia (GA group, n=25) or GA plus ultrasound-guided PVB (GA+PVB group, n=15) for the surgery. Pain scores and areal distribution of pain were compared between the two groups 1 hour and 6 hours postoperatively and on the midmorning of postoperative Day 1 (POD1). The QoR scores were compared between the two groups 6 hours postoperatively and on the midmorning of POD1. Incidence of postoperative nausea and vomiting and doses of analgesics and narcotics given were also compared. RESULTS: Pain scores at rest were significantly lower in the GA+PVB group at all designated time points [1 hour (p<0.0001), 6 hours (p<0.0001), and on midmorning of POD1 (p=0.041)]. Pain scores with movements was also significantly lower at all time points in the GA+PVB group (1 hour, p<0.0001; 6 hours, p<0.0001; midmorning of POD1, p=0.0012). Areal distribution of pain at rest and with movement was wider in the GA group 1 hour and 6 hours postoperately but was identical to that of GA+ PVB group on the mid-morning of POD1 [1 hour postoperatively at rest (p<0.0001), with movement (p<0.0001); 6 hours postoperatively at rest (p=0.0018), with movement (p=0.0048)]. The QoR scores were significantly higher in the GA+PVB group at 6 hours (p<0.0001) and on midmorning of POD1 (p=0.0079). The incidences of postoperative nausea and vomiting were significantly lower in the GA+PVB group (p=0.0004). Doses of postoperative analgesics and narcotics were significantly less in the GA+PVB group (p<0.0001 and p=0.001, respectively). Time to first request for analgesics was significantly longer in the GA+PVB group (p=0.0002). CONCLUSIONS: PVB given before surgery in combination with GA could provide better postoperative analgesia and better QoR than did GA alone in patients undergoing surgery for unilateral breast cancer.

A simple, innovative way to reduce rhinitis symptoms after sedation during endoscopy.

BACKGROUND: Supplmental oxygen is routinely given via nasal cannula (NC) to patients undergoing moderate sedation for endoscopy. Some patients complain of profuse rhinorrhea and/or sneezing after the procedure, which results in additional medical costs and patient dissatisfaction. OBJECTIVES: To determine the causal relationship between the route of oxygen delivery and troublesome nasal symptoms, and to seek possible solutions. METHODS: Patients (n=836) were randomly assigned to one of the three following groups: the NC group (n=294), the trimmed NC (TNC) group (n=268) and the nasal mask (NM) group (n=274). All received alfentanil 12.5 µg/kg and midazolam 0.06 mg/kg, and adjunct propofol for sedation. Supplemental oxygen at a flow rate of 4 L/min was used in the NC and TNC groups, and 6 L/min in the NM group. The incidence of nasal symptoms and hypoxia were assessed. RESULTS: The incidence of rhinitis symptoms was significantly higher in the NC group (7.1%) than in the TNC (0.4%) and NM (0%) groups (P<0.001). The incidence of hypoxia was lower in the NC group (3.1%) (P=0.040). All hypoxia events were transient (ie, less than 30 s in duration). On spirometry, the mean value of the lowest saturation of peripheral oxygen was found to be significantly lower in the NM group (96.8%) than in the NC group (97.7%) (P=0.004). CONCLUSIONS: Trimming the NC or using NMs reduced the incidence of rhinitis symptoms; however, the incidence of hypoxia was higher. Further investigation regarding the efficiency of oxygen supplementation is warranted in the design of novel oxygen delivery devices.

A novel mechanism for GABA synthesis and packaging into synaptic vesicles.

This review focuses on the recent advances that were made in understanding the fundamental mechanisms of the regulation of l-glutamic acid decarboxylase (GAD; E.C. 4.1.1.15), the enzyme responsible for the synthesis of the major inhibitory neurotransmitter gamma-amino butyric acid (GABA). In the brain, there are two isoforms of GAD- GAD67 and GAD65, where 67 and 65 refer to their respective molecular weights in kDa. A number of neurodegenerative diseases are known to occur as a result of insufficient inhibition due to failure of GABA neurotransmission. Since the rate-limiting step in GABA biosynthesis is the decarboxylation of glutamate by GAD, it is important to understand how GAD is regulated. So far, we know that GAD is regulated at the transcriptional level by alternate splicing and at the post-translational level by protein phosphorylation, palmitoylation and activity-dependent cleavage. Here, we present new evidence of the presence of GAD65 associated with mitochondria in the axon terminal and project a model in which ATP generated by mitochondrial GAD65 may serve an important function in providing energy for GAD65 mediated GABA biosynthesis and packaging into synaptic vesicles by vesicular GABA transporter (VGAT).

Release properties on gelatin-gum arabic microcapsules containing camphor oil with added polystyrene.

In this study, gelatin blended with arabic gum microcapsules containing camphor oil with added polystyrene were fabricated by a compound coacervation method. The parameters of oil/wall volume ratio, emulsification stirring speed, concentration of cross-linking agent, treated time and oil release properties were investigated. In order to improve the constant release effect of camphor oil, oil-soluble polystyrene (PS) was used as a sustained release agent. The camphor oil release curves were expressed by the exponential equation: psi(t)=C(eq)(1-e(-t/tau)), where psi(t) represent the variant of camphor oil concentration in the operation environment, C(eq) as the equilibrium state, t as the release time and tau as time constant. C(eq) and tau are significant factors pertaining to the camphor oil release properties. The results indicated that, for the microcapsules, the optimal oil/wall volume ratio was 0.75 to achieve the encapsulation efficiency of 99.6 wt.%. The average particle size were 294.7+/-14.2 microm, 167.2+/-11.2 microm, 85.7+/-8.7 microm at the homogenization stirring speed of 500, 1000, and 2000 rpm, respectively. The effect of sustained oil release will increase whereas the stirring speed decreases and the concentration of glutaraldehyde (GA) and treated time increases. Along with the increasing of quantity of polystyrene added, C(eq) decreased and tau increased, indicating that the sustained oil release amount and the release rate depend on the quantity of PS considerably.

Directed evolution of D-sialic acid aldolase to L-3-deoxy-manno-2-octulosonic acid (L-KDO) aldolase.

An efficient L-3-deoxy-manno-2-octulosonic acid (L-KDO) aldolase was created by directed evolution from the Escherichia coli D-Neu5Ac (N-acetylneuraminic acid, D-sialic acid) aldolase. Five rounds of error-prone PCR and iterative screening were performed with sampling of 10(3) colonies per round. The specificity constant (kcat/Km) of the unnatural sugar L-KDO is improved to a level equivalent to the wild-type D-sialic acid aldolase for its natural substrate, D-Neu5Ac. The final evolved enzyme exhibits a >1,000-fold improved ratio of the specificity constant [kcat/Km (L-KDO)]/[kcat/Km (D-sialic acid)]. The protein sequence of the evolved aldolase showed eight amino acid changes from the native enzyme, with all of the observed changes occurring outside of the active site. Our effort demonstrates that an enzyme can be rapidly altered to accept enantiomeric substrates with screening of a small population of colonies iteratively toward the target substrate with improved catalytic efficiency. This work provides a method for the synthesis of enantiomeric sugars and for the study of enantiomeric catalysis affected by remote mutations.

One-pot synthesis of L-Fructose using coupled multienzyme systems based on rhamnulose-1-phosphate aldolase.

Two methods have been developed for the highly efficient enzymatic synthesis of L-fructose: one is based on rhamnulose-1-phosphate aldolase and acid phosphatase using racemic glyceraldehyde and dihydroxyacetone phosphate as substrates; the other is to generate enantiomerically pure L-glyceraldehyde in situ from glycerol for the aldol reaction, using galactose oxidase catalyzed oxidation of glycerol in the presence of catalase. Using this four-enzyme system, enantiomerically pure L-fructose was obtained. Using the more expensive dihydroxyacetone phosphate, the yield was 55% after purification.

Directed evolution of N-acetylneuraminic acid aldolase to catalyze enantiomeric aldol reactions.

Expanding the scope of substrate specificity and stereoselectivity is of current interest in enzyme catalysis. Using error-prone PCR for in vitro directed evolution, the Neu5Ac aldolase from Escherichia coli has been altered to improve its catalytic activity toward enantiomeric substrates including N-acetyl-L-mannosamine and L-arabinose to produce L-sialic acid and L-KDO, the mirror-image sugars of the corresponding naturally occurring D-sugars. The first generation variant containing two mutations (Tyr98His and Phe115Leu) outside the (alpha,beta)(8)-barrel active site exhibits an inversion of enantioselectivity toward KDO and the second generation variant contains an additional amino acid change Val251Ile outside the alpha,beta-barrel active site that improves the enantiomeric formation of L-sialic acid and L-KDO. The X-ray structure of the triple mutant epNanA.2.5 at 2.3A resolution showed no significant difference between the wild-type and the mutant enzymes. We probed the potential structural 'hot spot' of enantioselectivity with saturation mutagenesis at Val251, the mutated residue most proximal to the Schiff base forming Lys165. The selected variant had an increase in k(cat) via replacement with another hydrophobic residue, leucine. Further sampling of a larger sequence space with error-prone PCR selected a third generation variant with significant improvement in L-KDO catalysis and a complete reversal of enantioselectivity.

Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles.

l-Glutamic acid decarboxylase (GAD) exists as both membrane-associated and soluble forms in the mammalian brain. Here, we propose that there is a functional and structural coupling between the synthesis of gamma-aminobutyric acid (GABA) by membrane-associated GAD and its packaging into synaptic vesicles (SVs) by vesicular GABA transporter (VGAT). This notion is supported by the following observations. First, newly synthesized [(3)H]GABA from [(3)H]l-glutamate by membrane-associated GAD is taken up preferentially over preexisting GABA by using immunoaffinity-purified GABAergic SVs. Second, the activity of SV-associated GAD and VGAT seems to be coupled because inhibition of GAD also decreases VGAT activity. Third, VGAT and SV-associated Ca(2+)calmodulin-dependent kinase II have been found to form a protein complex with GAD. A model is also proposed to link the neuronal stimulation to enhanced synthesis and packaging of GABA into SVs.