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1.  A Simple Sodium Dodecyl Sulfate-assisted Sample Preparation Method for LC-MS-based Proteomics Applications 
Analytical Chemistry  2012;84(6):2862-2867.
Sodium dodecyl sulfate (SDS) is one of the most popular laboratory reagents used for biological sample extraction; however, the presence of this reagent in samples challenges LC-MS-based proteomics analyses because it can interfer with reversed-phase LC separations and electrospray ionization. This study reports a simple SDS-assisted proteomics sample preparation method facilitated by a novel peptide-level SDS removal step. In an initial demonstration, SDS was effectively (>99.9%) removed from peptide samples through ion substitution-mediated DS- precipitation using potassium chloride (KCl), and excellent peptide recovery (>95%) was observed for <20 μg peptides. Further experiments demonstrated the compatibility of this protocol with LC-MS/MS analyses. The resulting proteome coverage obtained for both mammalian tissues and bacterial samples was comparable to or better than that obtained for the same sample types prepared using standard proteomics preparation methods and analyzed using LC-MS/MS. These results suggest the SDS-assisted protocol is a practical, simple, and broadly applicable proteomics sample processing method, which can be particularly useful when dealing with samples difficult to solubilize by other methods.
doi:10.1021/ac203394r
PMCID: PMC3310275  PMID: 22339560
SDS removal; KDS precipitation; proteomics; sample preparation; LC-MS
2.  Continuous Femoral Nerve Blocks: Decreasing Local Anesthetic Concentration to Minimize Quadriceps Femoris Weakness 
Anesthesiology  2012;116(3):665-672.
Background
Whether decreasing the local anesthetic concentration during a continuous femoral nerve block results in less quadriceps weakness remains unknown.
Methods
Preoperatively, bilateral femoral perineural catheters were inserted in patients undergoing bilateral knee arthroplasty (n = 36) at a single clinical center. Postoperatively, right-sided catheters were randomly assigned to receive perineural ropivacaine of either 0.1% (basal 12 mL/h; bolus 4 mL) or 0.4% (basal 3 mL/h; bolus 1 mL), with the left catheter receiving the alternative concentration/rate in an observer- and subject-masked fashion. The primary endpoint was the maximum voluntary isometric contraction of the quadriceps femoris muscles the morning of postoperative day 2. Equivalence of treatments would be concluded if the 95% confidence interval for the difference fell within the interval of −20% to 20%. Secondary endpoints included active knee extension, passive knee flexion, tolerance to cutaneous electrical current applied over the distal quadriceps tendon, dynamic pain scores, opioid requirements, and ropivacaine consumption.
Results
Quadriceps maximum voluntary isometric contraction for limbs receiving 0.1% ropivacaine was a mean (SD) of 13 (8) N·m, versus 12 (8) N·m for limbs receiving 0.4% [intra-subject difference of 3 (40) percentage points; 95% CI −10 to 17; p = 0.63]. Because the 95% confidence interval fell within prespecified tolerances, we conclude that the effect of the two concentrations were equivalent. Similarly, there were no statistically significant differences in secondary endpoints.
Conclusions
For continuous femoral nerve blocks, we found no evidence that local anesthetic concentration and volume influence block characteristics, suggesting that local anesthetic dose (mass) is the primary determinant of perineural infusion effects.
doi:10.1097/ALN.0b013e3182475c35
PMCID: PMC3288409  PMID: 22293719
3.  Sub-10 nm Gate Length Graphene Transistors: Operating at Terahertz Frequencies with Current Saturation 
Scientific Reports  2013;3:1314.
Radio-frequency application of graphene transistors is attracting much recent attention due to the high carrier mobility of graphene. The measured intrinsic cut-off frequency (fT) of graphene transistor generally increases with the reduced gate length (Lgate) till Lgate = 40 nm, and the maximum measured fT has reached 300 GHz. Using ab initio quantum transport simulation, we reveal for the first time that fT of a graphene transistor still increases with the reduced Lgate when Lgate scales down to a few nm and reaches astonishing a few tens of THz. We observe a clear drain current saturation when a band gap is opened in graphene, with the maximum intrinsic voltage gain increased by a factor of 20. Our simulation strongly suggests it is possible to design a graphene transistor with an extraordinary high fT and drain current saturation by continuously shortening Lgate and opening a band gap.
doi:10.1038/srep01314
PMCID: PMC3575621  PMID: 23419782
4.  Catalytic activity of nanostructured Au: Scale effects versus bimetallic/bifunctional effects in low-temperature CO oxidation on nanoporous Au 
Summary
The catalytic properties of nanostructured Au and their physical origin were investigated by using the low-temperature CO oxidation as a test reaction. In order to distinguish between structural effects (structure–activity correlations) and bimetallic/bifunctional effects, unsupported nanoporous gold (NPG) samples prepared from different Au alloys (AuAg, AuCu) by selective leaching of a less noble metal (Ag, Cu) were employed, whose structure (surface area, ligament size) as well as their residual amount of the second metal were systematically varied by applying different potentials for dealloying. The structural and chemical properties before and after 1000 min reaction were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The catalytic behavior was evaluated by kinetic measurements in a conventional microreactor and by dynamic measurements in a temporal analysis of products (TAP) reactor. The data reveal a clear influence of the surface contents of residual Ag and Cu species on both O2 activation and catalytic activity, while correlations between activity and structural parameters such as surface area or ligament/crystallite size are less evident. Consequences for the mechanistic understanding and the role of the nanostructure in these NPG catalysts are discussed.
doi:10.3762/bjnano.4.13
PMCID: PMC3596058  PMID: 23503603
AuAg alloy; AuCu alloy; CO oxidation; dynamic studies; kinetics; nanoporous Au (NPG) catalyst; oxygen storage capacity (OSC); temporal analysis of products (TAP)
5.  IL-21 Promotes the Pathologic Immune Response to Pneumovirus Infection 
IL-21 is a cytokine with pleiotropic actions, promoting terminal differentiation of B cells, increased immunoglobulin production, and the development of Th17 and T follicular helper cells. IL-21 is also implicated in the development of autoimmune disease and has anti-tumor activity. Here we investigated the role of IL-21 in host-defense to pneumonia virus of mice (PVM), which initiates an infection in mice resembling that of respiratory syncytial virus disease in humans. We found that PVM-infected mice expressed IL-21 in lung CD4+ T cells. Following infection, Il21r-/- mice exhibited less lung infiltration by neutrophils than did WT mice and correspondingly had lower levels of the chemokine CXCL1 in bronchoalveolar lavage fluid and lung parenchyma. CD8+, CD4+, and γδ T-cell numbers were also lower in the lungs of PVM-infected Il21r-/- mice than in infected WT mice, with normal Th17 cytokines but diminished IL-6 production in PVM-infected Il21r-/- mice. Strikingly, Il21r-/- mice had enhanced survival following PVM-infection, and moreover, treatment of WT mice with soluble IL-21R-Fc fusion protein enhanced their survival. These data reveal that IL-21 promotes the pathogenic inflammatory effect of PVM and indicate that manipulating IL-21 signaling may represent an immunomodulatory strategy for controlling PVM and potentially other respiratory virus infections.
doi:10.4049/jimmunol.1100767
PMCID: PMC3277853  PMID: 22238461
6.  Ear Acupressure, Heart Rate, and Heart Rate Variability in Patients with Insomnia 
This high-tech “teleacupuncture study” describes a neurovegetative ear acupressure effect in patients with chronic insomnia by using heart rate variability analysis. Heart rate (HR) and heart rate variability (HRV) measurements in 31 patients (mean age ± SD: 54.3 ± 10.6 years) were performed under standardized conditions in Harbin, China, and the data analysis was performed in Graz, Austria. Similar to our previous clinical and basic teleacupuncture research works, the electrocardiograms (ECGs) were recorded by an HRV Medilog AR12 system during ear acupressure of the Shenmen point on the left ear. HR decreased significantly (P < 0.05) during and after acupressure stimulation. The effect was not visible after the first stimulation, rather it appeared in the phase following the second acupressure stimulation (10 min after the first stimulation). Total HRV showed significant stimulation-dependent increases (P < 0.05), immediately after each acupressure stimulation with a maximum after the third stimulation (20 min after the first stimulation), but there was no long-lasting effect. The present results can serve as a solid basis for the further investigations of auricular point stimulation for noninvasive complementary use in treating insomnia.
doi:10.1155/2013/763631
PMCID: PMC3583049  PMID: 23476702
7.  Suppression of Natural Killer Cells by Sorafenib Contributes to Prometastatic Effects in Hepatocellular Carcinoma 
PLoS ONE  2013;8(2):e55945.
Sorafenib, a multi-tyrosine kinase inhibitor, is a standard treatment for advanced hepatocellular carcinoma (HCC). The present study was undertaken to determine whether the growth and metastasis of HCC were influenced in mice receiving sorafenib prior to implantation with tumors, and to investigate the in-vivo and in-vitro effect of sorafenib on natural killer (NK) cells. In sorafenib-pretreated BALB/c nu/nu mice and C57BL/6 mice, tumor growth was accelerated, mouse survival was decreased, and lung metastasis was increased. However, the depletion of NK1.1+ cells in C57BL/6 mice eliminated sorafenib-mediated pro-metastatic effects. Sorafenib significantly reduced the number of NK cells and inhibited reactivity of NK cells against tumor cells, in both tumor-bearing and tumor-free C57BL/6 mice. Sorafenib down-regulated the stimulatory receptor CD69 in NK cells of tumor-bearing mice, but not in tumor-free mice, and inhibited proliferation of NK92-MI cells, which is associated with the blocking of the PI3K/AKT pathway, and inhibited cytotoxicity of NK cells in response to tumor targets, which was due to impaired ERK phosphorylation. These results suggest immunotherapeutic approaches activating NK cells may enhance the therapeutic efficacy of sorafenib in HCC patients.
doi:10.1371/journal.pone.0055945
PMCID: PMC3568028  PMID: 23409093
8.  Acupressure at the Meridian Acupoint Xiyangguan (GB33) Influences Near-Infrared Spectroscopic Parameters (Regional Oxygen Saturation) in Deeper Tissue of the Knee in Healthy Volunteers 
Up to now, it is still unknown whether microcirculation of deeper peripheral tissue (knee) can be modulated by acupuncture or acupressure on a meridian acupoint. The goal of this pilot study was to investigate possible effects of acupressure at the Xiyangguan acupoint (GB33) on the regional oxygen saturation of the deeper knee tissues by near-infrared spectroscopy (NIRS). Twelve healthy volunteers with a mean age of 23.8 ± 1.6 years were investigated. Acupressure stimulation was performed for 5 minutes at the Xiyangguan acupoint. The results of the controlled study showed a significant increase of the values of regional oxygen saturation on the stimulated side of the knee (P = 0.033), whereas the opposite side on the same knee showed insignificant changes. These results may serve as a valuable basis for monitoring a possible therapeutic effect (e.g., after Khalifa therapy) in patients with knee problems.
doi:10.1155/2013/370341
PMCID: PMC3582098  PMID: 23476689
9.  Identification of a Novel, Recurrent HEY1-NCOA2 Fusion in Mesenchymal Chondrosarcoma based on a Genome-wide Screen of Exon-level Expression Data 
Genes, chromosomes & cancer  2011;51(2):127-139.
Cancer gene fusions that encode a chimeric protein are often characterized by an intragenic discontinuity in the RNA expression levels of the exons that are 5′ or 3′ to the fusion point in one or both of the fusion partners due to differences in the levels of activation of their respective promoters. Based on this, we developed an unbiased, genome-wide bioinformatic screen for gene fusions using Affymetrix Exon array expression data. Using a training set of 46 samples with different known gene fusions, we developed a data analysis pipeline, the “Fusion Score (FS) model”, to score and rank genes for intragenic changes in expression. In a separate discovery set of 41 tumor samples with possible unknown gene fusions, the FS model generated a list of 552 candidate genes. The transcription factor gene NCOA2 was one of the candidates identified in a mesenchymal chondrosarcoma. A novel HEY1-NCOA2 fusion was identified by 5′ RACE, representing an in-frame fusion of HEY1 exon 4 to NCOA2 exon 13. RT-PCR or FISH evidence of this HEY1-NCOA2 fusion was present in all additional mesenchymal chondrosarcomas tested with a definitive histologic diagnosis and adequate material for analysis (n=9) but was absent in 15 samples of other subtypes of chondrosarcomas. We also identified a NUP107-LGR5 fusion in a dedifferentiated liposarcoma but analysis of 17 additional samples did not confirm it as a recurrent event in this sarcoma type. The novel HEY1-NCOA2 fusion appears to be the defining and diagnostic gene fusion in mesenchymal chondrosarcomas.
doi:10.1002/gcc.20937
PMCID: PMC3235801  PMID: 22034177
10.  Fruit and vegetable intake and the risk of hypertension in middle-aged and older women 
American Journal of Hypertension  2011;25(2):180-189.
Background
Despite the promising findings from short-term intervention trials, the long-term effect of habitual fruit and vegetable intake on blood pressure (BP) remains uncertain. We therefore assessed the prospective association between baseline intake of fruits and vegetables and the risk of hypertension in a large cohort of middle-aged and older women.
Methods
We conducted analyses among 28,082 US female health professionals aged ≥39 years, free of cardiovascular disease, cancer, and hypertension at baseline. Baseline intake of fruits and vegetables was assessed using semi-quantitative food frequency questionnaires. Incident hypertension was identified from annual follow-up questionnaires.
Results
During 12.9 years of follow-up, 13,633 women developed incident hypertension. After basic adjustment including age, race, and total energy intake, the hazard ratio and 95% CI of hypertension was 0.97 (0.89-1.05), 0.93 (0.85-1.01), 0.89 (0.82-0.97), and 0.86 (0.78-0.94) comparing women who consumed 2-<4, 4-<6, 6-<8, and ≥8 servings/day of total fruits and vegetables with those consuming <2 servings/day. These associations did not change after additionally adjusting for lifestyle factors but were attenuated after further adjustment for other dietary factors. When fruits and vegetables were analyzed separately, higher intake of all fruits but not all vegetables remained significantly associated with reduced risk of hypertension after adjustment for lifestyle and dietary factors. Adding body mass index to the models eliminated all associations.
Conclusions
Higher intake of fruits and vegetables, as part of a healthy dietary pattern, may only contribute a modest beneficial effect to hypertension prevention, possibly through improvement in body weight regulation.
doi:10.1038/ajh.2011.186
PMCID: PMC3258456  PMID: 21993367
fruits; vegetables; diet; hypertension; prospective; women
12.  The Influence of Zusanli and Nonmeridian Acupuncture Points on the Survival Rate and Intestinal Tissue Features after Fatal Hemorrhagic Shock in Rats 
Sixty Sprague-Dawley rats were divided into 5 groups: (a) control group (HS); (b) Immediate rehydration group (IFR); (c) ST36 electroacupuncture (EA) delay rehydration group (EA/DFR): EA at ST36 immediately after blood loss with infusion 3 h later; (d) EA nonmeridian rehydration group (SEA/DFR): EA at nonacupuncture sites with rehydration similar to EA/DFR; (e) ST36 EA group (EA): EA at ST36 immediately after blood loss with no rehydration. Forty-five percent of the entire blood volume was taken out to make lethal hemorrhagic shock models. We recorded the survival rate, intestinal tissue DAO content, and microcirculation. The survival rate of the EA/DFR group and the IFR group was significantly higher than that of the other three groups (P < 0.05). Twelve hours after blood loss, intestinal tissue DAO content of the EA/DFR group and the IFR group was significantly higher than that of the SEA/DFR group, EA group, and HS group (P < 0.05 and P < 0.01). The mucosal blood flow of the EA/DFR group and the IFR group was significantly higher than the other groups (P < 0.05 each). We conclude that EA improves the blood pressure and raises the early survival rate of hemorrhagic shock rats, maintains the intestinal barrier function, and improves the degree of intestinal ischemia.
doi:10.1155/2013/750620
PMCID: PMC3570926  PMID: 23431347
13.  The Use of Propofol as a Sedative Agent in Gastrointestinal Endoscopy: A Meta-Analysis 
PLoS ONE  2013;8(1):e53311.
Objectives
To assess the efficacy and safety of propofol sedation for gastrointestinal endoscopy, we conducted a meta-analysis of randomized controlled trials (RCTs) comparing propofol with traditional sedative agents.
Methods
RCTs comparing the effects of propofol and traditional sedative agents during gastrointestinal endoscopy were found on MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE. Cardiopulmonary complications (i.e., hypoxia, hypotension, arrhythmia, and apnea) and sedation profiles were assessed.
Results
Twenty-two original RCTs investigating a total of 1,798 patients, of whom 912 received propofol only and 886 received traditional sedative agents only, met the inclusion criteria. Propofol use was associated with shorter recovery (13 studies, 1,165 patients; WMD –19.75; 95% CI –27.65, 11.86) and discharge times (seven studies, 471 patients; WMD –29.48; 95% CI –44.13, –14.83), higher post-anesthesia recovery scores (four studies, 503 patients; WMD 2.03; 95% CI 1.59, 2.46), better sedation (nine studies, 592 patients; OR 4.78; 95% CI 2.56, 8.93), and greater patient cooperation (six studies, 709 patients; WMD 1.27; 95% CI 0.53, 2.02), as well as more local pain on injection (six studies, 547 patients; OR 10.19; 95% CI 3.93, 26.39). Effects of propofol on cardiopulmonary complications, procedure duration, amnesia, pain during endoscopy, and patient satisfaction were not found to be significantly different from those of traditional sedative agents.
Conclusions
Propofol is safe and effective for gastrointestinal endoscopy procedures and is associated with shorter recovery and discharge periods, higher post-anesthesia recovery scores, better sedation, and greater patient cooperation than traditional sedation, without an increase in cardiopulmonary complications. Care should be taken when extrapolating our results to specific practice settings and high-risk patient subgroups.
doi:10.1371/journal.pone.0053311
PMCID: PMC3540096  PMID: 23308191
14.  HIV-1 gp120 Vaccine Induces Affinity Maturation in both New and Persistent Antibody Clonal Lineages 
Journal of Virology  2012;86(14):7496-7507.
Most antibodies that broadly neutralize HIV-1 are highly somatically mutated in antibody clonal lineages that persist over time. Here, we describe the analysis of human antibodies induced during an HIV-1 vaccine trial (GSK PRO HIV-002) that used the clade B envelope (Env) gp120 of clone W6.1D (gp120W6.1D). Using dual-color antigen-specific sorting, we isolated Env-specific human monoclonal antibodies (MAbs) and studied the clonal persistence of antibodies in the setting of HIV-1 Env vaccination. We found evidence of VH somatic mutation induced by the vaccine but only to a modest level (3.8% ± 0.5%; range 0 to 8.2%). Analysis of 34 HIV-1-reactive MAbs recovered over four immunizations revealed evidence of both sequential recruitment of naïve B cells and restimulation of previously recruited memory B cells. These recombinant antibodies recapitulated the anti-HIV-1 activity of participant serum including pseudovirus neutralization and antibody-dependent cell-mediated cytotoxicity (ADCC). One antibody (3491) demonstrated a change in specificity following somatic mutation with binding of the inferred unmutated ancestor to a linear C2 peptide while the mutated antibody reacted only with a conformational epitope in gp120 Env. Thus, gp120W6.1D was strongly immunogenic but over four immunizations induced levels of affinity maturation below that of broadly neutralizing MAbs. Improved vaccination strategies will be needed to drive persistent stimulation of antibody clonal lineages to induce affinity maturation that results in highly mutated HIV-1 Env-reactive antibodies.
doi:10.1128/JVI.00426-12
PMCID: PMC3416280  PMID: 22553329
15.  Personal characteristics related to the risk of adolescent internet addiction: a survey in Shanghai, China 
BMC Public Health  2012;12:1106.
Background
Paralleling the rapid growth in computers and internet connections, adolescent internet addiction (AIA) is becoming an increasingly serious problem, especially in developing countries. This study aims to explore the prevalence of AIA and associated symptoms in a large population-based sample in Shanghai and identify potential predictors related to personal characteristics.
Methods
In 2007, 5,122 adolescents were randomly chosen from 16 high schools of different school types (junior, senior key, senior ordinary and senior vocational) in Shanghai with stratified-random sampling. Each student completed a self-administered and anonymous questionnaire that included DRM 52 Scale of Internet-use. The DRM 52 Scale was adapted for use in Shanghai from Young’s Internet Addiction Scale and contained 7 subscales related to psychological symptoms of AIA. Multiple linear regression and logistic regression were both used to analyze the data.
Results
Of the 5,122 students, 449 (8.8%) were identified as internet addicts. Although adolescents who had bad (vs. good) academic achievement had lower levels of internet-use (p < 0.0001), they were more likely to develop AIA (odds ratio 4.79, 95% CI: 2.51-9.73, p < 0.0001) and have psychological symptoms in 6 of the 7 subscales (not in Time-consuming subscale). The likelihood of AIA was higher among those adolescents who were male, senior high school students, or had monthly spending >100 RMB (all p-values <0.05). Adolescents tended to develop AIA and show symptoms in all subscales when they spent more hours online weekly (however, more internet addicts overused internet on weekends than on weekdays, p < 0.0001) or when they used the internet mainly for playing games or real-time chatting.
Conclusions
This study provides evidence that adolescent personal factors play key roles in inducing AIA. Adolescents having aforementioned personal characteristics and online behaviors are at high-risk of developing AIA that may compound different psychological symptoms associated with AIA. Spending excessive time online is not in itself a defining symptom of AIA. More attention is needed on adolescent excessive weekend internet-use in prevention of potential internet addicts.
doi:10.1186/1471-2458-12-1106
PMCID: PMC3563549  PMID: 23259906
Adolescent; Internet addiction; Risk factors; China
16.  Time-dependent universal conductance fluctuations in IrO2 nanowires 
Nanoscale Research Letters  2012;7(1):673.
Single-crystalline iridium dioxide nanowires show the time-dependent universal conductance fluctuations (TUCFs) at cryogenic temperatures. The conductance fluctuations persist up to temperature T as high as nearly 10 K. The root-mean-square TUCF magnitudes increase with decreasing T, reaching approximately 0.1 e2 / h at 1.7 K. We ascribe these conductance fluctuations to originating from the conduction electrons scattering upon mobile defects (moving scattering centers). Our measured TUCF characteristics are satisfactorily explained in terms of the existing TUCF theory in its three-dimensional form. The extracted electron dephasing length Lφ(1.7 K) ≃90 nm is smaller than the diameter (≈ 180 nm) of our nanowires.
doi:10.1186/1556-276X-7-673
PMCID: PMC3582475  PMID: 23237379
Quantum-interference effect; Universal conductance fluctuation; Mobile defect; Iridium dioxide nanowire; Rutile structure
17.  NeutroPhase® in chronic non-healing wounds 
Chronic non-healing wounds, such as venous stasis ulcers, diabetic ulcers, and pressure ulcers are serious unmet medical needs that affect a patient’s morbidity and mortality. Common pathogens observed in chronic non-healing wounds are Staphylococcus including MRSA, Pseudomonas, Enterobacter, Stenotrophomonas, and Serratia spp. Topical and systemically administered antibiotics do not adequately decrease the level of bacteria or the associated biofilm in chronic granulating wounds and the use of sub-lethal concentrations of antibiotics can lead to resistant phenotypes. Furthermore, topical antiseptics may not be fully effective and can actually impede wound healing. We show 5 representative examples from our more than 30 clinical case studies using NeutroPhase® as an irrigation solution with chronic non-healing wounds with and without the technique of negative pressure wound therapy (NPWT). NeutroPhase® is pure 0.01% hypochlorous acid (i.e. >97% relative molar distribution of active chlorine species as HOCl) in a 0.9% saline solution at pH 4-5 and is stored in glass containers. NovaBay has three FDA cleared 510(k)s. Patients showed a profound improvement and marked accelerated rates of wound healing using NeutroPhase® with and without NPWT. NeutroPhase® was non-toxic to living tissues.
PMCID: PMC3523395  PMID: 23272294
NeutroPhase®; hypochlorous acid; chronic non-healing wounds; 510(k); negative pressure wound therapy (NPWT)
18.  1-{(Z)-1-(2,4-Dichloro­phen­yl)-1-[2-(4-methyl­phen­oxy)eth­oxy]prop-1-en-2-yl}-1H-imidazol-3-ium nitrate 
In the title salt, C21H21Cl2N2O2 +·NO3 −, the imidazole ring makes dihedral angles of 43.39 (14) and 10.9 (2)° with the 4-methyl­phenyl and 2,4-dichloro­phenyl rings, respectively. The mol­ecule adopts a Z conformation about the C=C double bond, which links the imidazole ring to the 4-methyl­phen­oxy unit via an eth­oxy chain. In the crystal, cations and anions are linked into chains by N—H⋯O and C—H⋯O hydrogen bonds.
doi:10.1107/S1600536812046181
PMCID: PMC3588376  PMID: 23476414
19.  A Transcontinental Pilot Study for Acupuncture Lifting-Thrusting and Twisting-Rotating Manipulations 
The goal of this study was to observe possible changes of the skin microvascular perfusion on the acupoints and related areas and to quantify influences of acupuncture stimulation on the volunteers' blood pressure, heart rate, and heart rate variability (HRV). During the measurement, the needling sensations of volunteers were enquired and recorded. Ten healthy volunteers with a mean age ± SD of 25.4 ± 2.6 years were enrolled, and acupuncture stimulation was performed on ST36 (Zusanli, right side), in pure lifting-thrusting or twisting-rotating manipulation. During needling, we observed the changing of microvascular perfusion on ST36, 37, 38, and a control point using MOOR speckle laser blood flow scanning. Electrocardiogram and blood pressure were registered before, during, and after needling. Both lifting-thrusting and twisting-rotating needle manipulations could decrease blood pressure and heart rate while improving HRV significantly. There were significant differences in microvascular perfusion on acupoints ST36, 37, 38, and the control point following these two kinds of needle manipulation. The needling sensation caused by lifting-thrusting is stronger than that of twisting-rotating manipulation. Significant differences between lifting-thrusting and twisting-rotating acupuncture stimulation methods show that the mechanisms may be different and need to be researched thoroughly in the future.
doi:10.1155/2012/157989
PMCID: PMC3518771  PMID: 23243429
20.  Intersubband absorption properties of high Al content AlxGa1−xN/GaN multiple quantum wells grown with different interlayers by metal organic chemical vapor deposition 
Nanoscale Research Letters  2012;7(1):649.
High Al content AlxGa1−xN/GaN multiple quantum well (MQW) films with different interlayers were grown by metal organic chemical vapor deposition. These MQWs were designed to achieve intersubband (ISB) absorption in the mid-infrared spectral range. We have considered two growth conditions, with AlGaN interlayer and GaN/AlN superlattice (SL) interlayer, both deposited on GaN-on-sapphire templates. Atomic force microscopy images show a relatively rough surface with atomic-step terraces and surface depression, mainly dominated by dislocations. High-resolution X-ray diffraction and transmission electron microscopy analyses indicate that good crystalline quality of the AlGaN/GaN MQW layer could be achieved when the AlGaN interlayer is inserted. The ISB absorption with a peak at 3.7 μm was demonstrated in MQW films with AlGaN interlayer. However, we have not observed the infrared absorption in MQW films with GaN/AlN SL interlayer. It is believed that the high dislocation density and weaker polarization that resulted from the rough interface are determinant factors of vanished ISB absorption for MQW films with the GaN/AlN SL interlayer.
doi:10.1186/1556-276X-7-649
PMCID: PMC3526456  PMID: 23181766
Quantum wells; Interface; Intersubband; TEM; PACS; 61.72.Lk; 61.05.cp; 68.37.-d; 61.72.uj
21.  Optimization of Dosing for EGFR-Mutant Non–Small Cell Lung Cancer with Evolutionary Cancer Modeling 
Science translational medicine  2011;3(90):90ra59.
Non–small cell lung cancers (NSCLCs) that harbor mutations within the epidermal growth factor receptor (EGFR) gene are sensitive to the tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. Unfortunately, all patients treated with these drugs will acquire resistance, most commonly as a result of a secondary mutation within EGFR (T790M). Because both drugs were developed to target wild-type EGFR, we hypothesized that current dosing schedules were not optimized for mutant EGFR or to prevent resistance. To investigate this further, we developed isogenic TKI-sensitive and TKI-resistant pairs of cell lines that mimic the behavior of human tumors. We determined that the drug-sensitive and drug-resistant EGFR-mutant cells exhibited differential growth kinetics, with the drug-resistant cells showing slower growth. We incorporated these data into evolutionary mathematical cancer models with constraints derived from clinical data sets. This modeling predicted alternative therapeutic strategies that could prolong the clinical benefit of TKIs against EGFR-mutant NSCLCs by delaying the development of resistance.
doi:10.1126/scitranslmed.3002356
PMCID: PMC3500629  PMID: 21734175
22.  Nonparametric Regression With Missing Outcomes Using Weighted Kernel Estimating Equations 
We consider nonparametric regression of a scalar outcome on a covariate when the outcome is missing at random (MAR) given the covariate and other observed auxiliary variables. We propose a class of augmented inverse probability weighted (AIPW) kernel estimating equations for nonparametric regression under MAR. We show that AIPW kernel estimators are consistent when the probability that the outcome is observed, that is, the selection probability, is either known by design or estimated under a correctly specified model. In addition, we show that a specific AIPW kernel estimator in our class that employs the fitted values from a model for the conditional mean of the outcome given covariates and auxiliaries is double-robust, that is, it remains consistent if this model is correctly specified even if the selection probabilities are modeled or specified incorrectly. Furthermore, when both models happen to be right, this double-robust estimator attains the smallest possible asymptotic variance of all AIPW kernel estimators and maximally extracts the information in the auxiliary variables. We also describe a simple correction to the AIPW kernel estimating equations that while preserving double-robustness it ensures efficiency improvement over nonaugmented IPW estimation when the selection model is correctly specified regardless of the validity of the second model used in the augmentation term. We perform simulations to evaluate the finite sample performance of the proposed estimators, and apply the methods to the analysis of the AIDS Costs and Services Utilization Survey data. Technical proofs are available online.
doi:10.1198/jasa.2010.tm08463
PMCID: PMC3491912  PMID: 23144520
Asymptotics; Augmented kernel estimating equations; Double robustness; Efficiency; Inverse probability weighted kernel estimating equations; Kernel smoothing
23.  No Decrease in Susceptibility to NVC-422 in Multiple-Passage Studies with Methicillin-Resistant Staphylococcus aureus, S. aureus, Pseudomonas aeruginosa, and Escherichia coli 
Twenty-five serial passages of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and 50 passages of methicillin-resistant Staphylococcus aureus resulted in no significant increase in NVC-422 MICs, while ciprofloxacin MICs increased 256-fold for E. coli and 32-fold for P. aeruginosa and S. aureus. Mupirocin, fusidic acid, and retapamulin MICs for MRSA increased 64-, 256-, and 16-fold, respectively. No cross-resistance to NVC-422 was observed with mupirocin-, fusidic acid-, and retapamulin-resistant strains.
doi:10.1128/AAC.05985-11
PMCID: PMC3346591  PMID: 22354299
24.  A new dynamic model of three cell interactions for CTL responses 
Oncoimmunology  2012;1(8):1430-1432.
The exact mechanisms of CD4 help in the generation of memory cytotoxic T lymphocytes (CTLs) remain largely illusive. We propose that dendritic cells (DCs) first interact with CD4+ T cells, resulting in DC licensing and CD4+ T-cell priming. Thereafter, CD8+ T cells can receive stimulatory signals from DC-CD4+ T-cell clusters and as well as individually from licensed DCs and primed CD4+ T cells.
doi:10.4161/onci.21175
PMCID: PMC3518527  PMID: 23243618
CD4 help; CD40-CD40L; CTL response; dendritic cells; two-photon
25.  Observation of Microvascular Perfusion in the Hegu (LI4) Acupoint Area after Deqi Acupuncture at Quchi (LI11) Acupoint Using Speckle Laser Blood Flow Scanning Technology 
The aim of this study was to investigate the traditional meridian theory using speckle laser blood flow scanning technology to observe microcirculation of the Hegu acupoint area after acupuncture stimulation on distant points. An observational study was conducted to observe the microvascular perfusion of Hegu (LI4) and control points after acupuncturing Quchi (LI11). Thirty healthy volunteers (mean age 31.6 ± 8.7 years) received deqi acupuncture on Quchi (LI11, right side), and simultaneously changes in microvascular perfusion of Sanjian (LI3), Hegu (LI4), Yangxi (LI5), and two control points were observed before, during, and after needling using a MOOR speckle laser. The results showed that the changes in microvascular perfusion of the observed points are not regular. After correction, the experiment showed that the blood perfusion on 3 meridian acupoints was increased while the perfusion on 2 control points was decreased following acupuncture stimulation, the changes at Hegu (LI4) being the statistically most significant ones. Deqi acupuncture can help in regulating the body's blood flow, with a certain degree of meridian specificity.
doi:10.1155/2012/604590
PMCID: PMC3522481  PMID: 23258991

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