GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment

Background: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. Methods: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. Results: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups. Conclusion: In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary

An experimental and kinetic modeling study of the auto-ignition delay times of trimethyl phosphate-in-air mixtures

Organophosphorus compounds (OPCs) are known to be combustion inhibitors (CI), fire suppressants, or flame retardant molecules (FRMs) for polymers and as surrogates (simulants) for the disposal or thermal degradation of chemical war agents (CWAs). Despite a significant number of studies on the mechanism of their action, OPCs’ combustion chemistry is still insufficiently understood. There is a need for further understanding of their auto-ignition and oxidation characteristics at relevant conditions (high pressures and low temperatures). This study reports on new data on the autoignition delays of Trimethyl Phosphate (TMP)-in-air mixtures obtained from experiments performed on a high-pressure shock tube (HPST) at pressures of 5 and 10 bar in the initial temperature range from 1200 to 2200 K. An updated TMP kinetic model deduced from the Glaude et al. model for the thermal degradation of OPCs is also proposed for the estimation of the autoignition delays of the studied mixtures by incorporating new reaction pathways and corresponding rate constants estimation of some reactions involving TMP and some intermediate products of its degradation. The results indicate that the proposed model is in satisfactory agreement with all the investigated mixtures

Experimental study of yarn friction slip and fabric shear deformation in yarn pull-out test

When designing circuits, engineers need to know the voltages and intensities at every point in the circuit. In simple circuits the results can be calculated by hand by using complex numbers, but in complex circuits this is impossible. This is why, nowadays, recourse is had to computer simulation so that circuits can be designed before being built, since it eliminates the need to build prototypes of the circuits with the ensuing time and cost. Bond-graph technique is a visual methodology that adds more transparency to the processes and it has turned out to be remarkably useful as it is a simple, effective method that can be applied to any physical system where there is a power exchange.This work initially analyses the starting mechanism of a direct current machine using bond graph technique, compares it with a model developed in Simulink copy and then stabilises the running of the motor by using a type PI controller

Surface enhanced Raman spectroscopy based biosensor with a microneedle array for minimally invasive in vivo glucose measurements

To monitor blood glucose levels reliably, diabetic patients usually have to undergo frequent fingerstick tests to draw out fresh blood, which is painful and inconvenient with the potential risk of cross contamination especially when the lancet is reused or not properly sterilized. This work reports a novel surface-enhanced Raman spectroscopy (SERS) sensor for the in situ intradermal detection of glucose based on a low-cost poly(methyl methacrylate) microneedle (PMMA MN) array. After incorporating 1-decanethiol (1-DT) onto the silver-coated array surface, the sensor was calibrated in the range of 0–20 mM in skin phantoms then tested for the in vivo quantification of glucose in a mouse model of streptozocin (STZ)-induced type I diabetes. The results showed that the functional poly(methyl methacrylate) microneedle (F-PMMA MN) array was able to directly measure glucose in the interstitial fluid (ISF) in a few minutes and retain its structural integrity without swelling. The Clarke error grid analysis of measured data indicated that 93% of the data points lie in zones A and B. Moreover, the MN array exhibited minimal invasiveness to the skin as the skin recovered well without any noticeable adverse reaction in 10 min after measurements. With further improvement and proper validation, this polymeric MN array-based SERS biosensor has the potential to be used in painless glucose monitoring of diabetic patients in the future.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)National Medical Research Council (NMRC)Accepted versionQ.L. acknowledges the funding support from the Ministry of Education in Singapore under its Tier 2 grants (Nos. MOE2015-T2-2-112 and MOE2017-T2-2-057) and Tier 1 grant (RG129/19), Agency for Science, Technology and Research (A*STAR) under its Industry Alignment Fund (Pre-Positioning) (Grant No. H17/01/a0/008 and H17/01/a0/0F9), and KK Women’s And Children’s Hospital (KKHHF/2018/09). C.X. acknowledges the funding support from Singapore Agency for Science, Technology and Research (A*STAR), Science and Engineering Research Council Additive Manufacturing for Biological Materials (AMBM) program (A18A8b0059), and an internal grant from City University of Hong Kong (#9610472). X.W. acknowledges the funding support from National Medical Research Council Singapore Large Collaborative Grant DYNAMO (to X.W.NMRC/OFLCG/001/2017) and National Medical Research Council Singapore Large Collaborative Grant TAAP (to X.W.NMRC/OFLCG/004/2018)

Nanoparticle Formulation of Moxifloxacin and Intramuscular Route of Delivery Improve Antibiotic Pharmacokinetics and Treatment of Pneumonic Tularemia in a Mouse Model

Francisella tularensis causes a serious and often fatal infection, tularemia. We compared the efficacy of moxifloxacin formulated as free drug vs disulfide snap-top mesoporous silica nanoparticles (MSNs) in a mouse model of pneumonic tularemia. We found that MSN-formulated moxifloxacin was more effective than free drug and that the intramuscular and subcutaneous routes were markedly more effective than the intravenous route. Measurement of tissue silica levels and fluorescent flow cytometry assessment of colocalization of MSNs with infected cells revealed that the enhanced efficacy of MSNs and the intramuscular route of delivery was not due to better delivery of MSNs to infected tissues or cells. However, moxifloxacin blood levels demonstrated that the nanoparticle formulation and intramuscular route provided the longest half-life and longest time above the minimal inhibitory concentration. Thus, improved pharmacokinetics are responsible for the greater efficacy of nanoparticle formulation and intramuscular delivery compared with free drug and intravenous delivery

Nanoparticle Formulation of Moxifloxacin and Intramuscular Route of Delivery Improve Antibiotic Pharmacokinetics and Treatment of Pneumonic Tularemia in a Mouse Model.

Francisella tularensis causes a serious and often fatal infection, tularemia. We compared the efficacy of moxifloxacin formulated as free drug vs disulfide snap-top mesoporous silica nanoparticles (MSNs) in a mouse model of pneumonic tularemia. We found that MSN-formulated moxifloxacin was more effective than free drug and that the intramuscular and subcutaneous routes were markedly more effective than the intravenous route. Measurement of tissue silica levels and fluorescent flow cytometry assessment of colocalization of MSNs with infected cells revealed that the enhanced efficacy of MSNs and the intramuscular route of delivery was not due to better delivery of MSNs to infected tissues or cells. However, moxifloxacin blood levels demonstrated that the nanoparticle formulation and intramuscular route provided the longest half-life and longest time above the minimal inhibitory concentration. Thus, improved pharmacokinetics are responsible for the greater efficacy of nanoparticle formulation and intramuscular delivery compared with free drug and intravenous delivery