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تعتبر غرف الحاضنات للأطفال حديثي الولادة من أكثر البيئات تعرضاً للضجيج بسبب الكادر والتجهيزات ذات الإنذارات الصوتية. ويعتبر التعرض للضجيج مسبباً لمخاطر تتعلق بتطور الجهاز السمعي، زيادة معدل التنفس وضربات القلب، ارتفاع ضغط الدم والتوتر. ويهدف البحث لقياس مستوى الشدة الصوتية (الضجيج) وتحسين البيئة الصوتية داخل غرفة الحاضنات موضوع البحث. وسنحاول في هذه الدراسة التعرف على الخصائص الفيزيائية للصوت وكيفية قياس الضجيج في إحدى غرف الحاضنات في إحدى المستشفيات، لتحديد قيم الضجيج في الغرفة خلال فترات زمنية وحالات مختلفة. محاولين تحديد الأماكن الأكثر تعرضاً للضجيج، ومصادر هو مقارنة قيم مستويات الضجيج مع القيم المعيارية الموضوعة من قبل الأكاديمية الأمريكية لطب الأطفال AAP (American Academy of Pediatrics)؛ وذلك لحماية الأطفال والكادر من التعرض لها. انطلقنا في هذا البحث من مجموعة من الدراسات السابقة التي أجريت في غرف حاضنات الأطفال. استخدمنا لقياس الضجيج أربعة أجهزة قياس لمستوى الشدة الصوتية، وقد تبين أن أغلب القيم المقاسة تتجاوز القيم المعيارية الموضوعة من قبل الأكاديمية الأمريكية لطب الأطفال AAP. لذا كان من الواجب زيادة الوعي حول الآثار السلبية للضجيج داخل غرف حواضن الأطفال، وتنفيذ برامج لتخفيضها.

This activity uses podcasts to model narrative writing techniques. The challenges students face when exercising narrative writing skills are unique when compared to those of persuasive and expository writing; my students have repeatedly expressed their qualms with articulating experiences that engage their audience. Although students have extensive exposure to literary works, both in their native language and in English, fostering creativity and incorporating narrative elements based on their own experiences has caused panic. The more creativity a task was expected to generate, the more students' confidence was undermined. Podcasts present a creative, nontraditional model of narration for students.

BackgroundThe Resistance-Nodulation-Division (RND) family transporter AcrB plays a major role in the intrinsic and increased resistance of Escherichia coli to a large number of antibiotics. The distal binding pocket within this multidrug efflux transporter is very large, but the effort to define the roles of various residues facing this pocket through site-directed mutagenesis so far involved only the determination of minimal inhibitory concentrations of drugs in mutants.MethodsWe measured in intact E. coli cells the kinetics of efflux of two substrates, nitrocefin (a cephalosporin) that is predicted mainly to bind to the upper, "groove" domain of the pocket, and L-alanyl-β-naphthylamide (Ala-Naph) that is likely to bind to the lower, "cave" domain, in a number of site-directed mutants of AcrB, where a hydrophobic or aromatic residue was changed into alanine.ResultsThe efflux of nitrocefin became attenuated by some mutations in the groove domain, such as I278A and F178A, but in some experiments a mutation in the cave domain, F628A produced a similar result. In some cases an increased value of KM was detected. The efflux of Ala-Naph was increased by mutations in the cave domain, such as F136A and I626A, but also by those in the groove domain (I277A, I278A, F178A). In most cases the increased Vmax values appeared to be responsible. F610A mutation had a profound effect on the efflux of both substrates, as reported earlier.ConclusionsOur data show for the first time effects of various substrate-binding pocket mutations on the kinetics of efflux of two substrates by the AcrB pump. They also confirm interactions between substrates and drugs predicted by MD simulation studies, and also reveal areas that need future research.

Efflux pumps of the resistance-nodulation division superfamily, such as AcrB, make a major contribution to multidrug resistance in Gram-negative bacteria. Inhibitors of such pumps would improve the efficacy of antibiotics, and ameliorate the crisis in health care caused by the prevalence of multidrug resistant Gram-negative pathogens. Phenylalanyl-arginine β-naphthylamide (PAβN), is a well-known inhibitor of AcrB and its homologs. However, its mechanism of inhibition is not clear. Because the hydrolysis of PAβN in Escherichia coli was nearly entirely dependent on an aminopeptidase, PepN, expression of PepN in periplasm allowed us to carry out a quantitative determination of PAβN efflux kinetics through the determination of its periplasmic concentrations by quantitation of the first hydrolysis product, phenylalanine, after a short period of treatment. We found that PAβN is efficiently pumped out by AcrB, with a sigmoidal kinetics. We also examined the behavior of PAβN homologs, Ala β-naphthylamide, Arg β-naphthylamide, and Phe β-naphthylamide, as substrates of AcrB and as modulators of nitrocefin efflux through AcrB. Furthermore, molecular dynamics simulations indicated that the mode of binding of these compounds to AcrB affects the modulatory activity on the efflux of other substrates. These results, and the finding that PAβN changes the nitrocefin kinetics into a sigmoidal one, suggested that PAβN inhibited the efflux of other drugs by binding to the bottom of the distal binding pocket, the so-called hydrophobic trap, and also by interfering with the binding of other drug substrates to the upper part of the binding pocket.

UnlabelledThe AcrB protein of Escherichia coli, together with TolC and AcrA, forms a contiguous envelope conduit for the capture and extrusion of diverse antibiotics and cellular metabolites. In this study, we sought to expand our knowledge of AcrB by conducting genetic and functional analyses. We began with an AcrB mutant bearing an F610A substitution in the drug binding pocket and obtained second-site substitutions that overcame the antibiotic hypersusceptibility phenotype conferred by the F610A mutation. Five of the seven unique single amino acid substitutions--Y49S, V127A, V127G, D153E, and G288C--mapped in the periplasmic porter domain of AcrB, with the D153E and G288C mutations mapping near and at the distal drug binding pocket, respectively. The other two substitutions--F453C and L486W--were mapped to transmembrane (TM) helices 5 and 6, respectively. The nitrocefin efflux kinetics data suggested that all periplasmic suppressors significantly restored nitrocefin binding affinity impaired by the F610A mutation. Surprisingly, despite increasing MICs of tested antibiotics and the efflux of N-phenyl-1-naphthylamine, the TM suppressors did not improve the nitrocefin efflux kinetics. These data suggest that the periplasmic substitutions act by influencing drug binding affinities for the distal binding pocket, whereas the TM substitutions may indirectly affect the conformational dynamics of the drug binding domain.ImportanceThe AcrB protein and its homologues confer multidrug resistance in many important human bacterial pathogens. A greater understanding of how these efflux pump proteins function will lead to the development of effective inhibitors against them. The research presented in this paper investigates drug binding pocket mutants of AcrB through the isolation and characterization of intragenic suppressor mutations that overcome the drug susceptibility phenotype of mutations affecting the drug binding pocket. The data reveal a remarkable structure-function plasticity of the AcrB protein pertaining to its drug efflux activity.

Although the discovery and characterization of multiple tumor antigens have sparked the development of many antigen/derived cancer vaccines, many are poorly immunogenic and thus, lack clinical efficacy. Adjuvants are therefore incorporated into vaccine formulations to trigger strong and long-lasting immune responses. Adjuvants have generally been classified into two categories: those that ‘depot’ antigens (e.g. mineral salts such as aluminum hydroxide, emulsions, liposomes) and those that act as immunostimulants (Toll Like Receptor agonists, saponins, cytokines). In addition, several novel technologies using vector-based delivery of antigens have been used. Unfortunately, the immune system declines with age, a phenomenon known as immunosenescence, and this is characterized by functional changes in both innate and adaptive cellular immunity systems as well as in lymph node architecture. While many of the immune functions decline over time, others paradoxically increase. Indeed, aging is known to be associated with a low level of chronic inflammation—inflamm-aging. Given that the median age of cancer diagnosis is 66 years and that immunotherapeutic interventions such as cancer vaccines are currently given in combination with or after other forms of treatments which themselves have immune-modulating potential such as surgery, chemotherapy and radiotherapy, the choice of adjuvants requires careful consideration in order to achieve the maximum immune response in a compromised environment. In addition, more clinical trials need to be performed to carefully assess how less conventional form of immune adjuvants, such as exercise, diet and psychological care which have all be shown to influence immune responses can be incorporated to improve the efficacy of cancer vaccines. In this review, adjuvants will be discussed with respect to the above-mentioned important elements.

The power of personalized medicine is based on a deep understanding of cellular and molecular processes underlying disease pathogenesis. Accurately characterizing and analyzing connections between these processes is dependent on our ability to access multiple classes of biomarkers (DNA, RNA, and proteins)—ideally, in a minimally processed state. Here, we characterize a biomarker isolation platform that enables simultaneous isolation and on-chip detection of cell-free DNA (cfDNA), extracellular vesicle RNA (EV-RNA), and EV-associated proteins in unprocessed biological fluids using AC Electrokinetics (ACE). Human biofluid samples were flowed over the ACE microelectrode array (ACE chip) on the Verita platform while an electrical signal was applied, inducing a field that reversibly captured biomarkers onto the microelectrode array. Isolated cfDNA, EV-RNA, and EV-associated proteins were visualized directly on the chip using DNA and RNA specific dyes or antigen-specific, directly conjugated antibodies (CD63, TSG101, PD-L1, GPC-1), respectively. Isolated material was also eluted off the chip and analyzed downstream by multiple methods, including PCR, RT-PCR, next-generation sequencing (NGS), capillary electrophoresis, and nanoparticle size characterization. The detection workflow confirmed the capture of cfDNA, EV-RNA, and EV-associated proteins from human biofluids on the ACE chip. Tumor specific variants and the mRNAs of housekeeping gene PGK1 were detected in cfDNA and RNA isolated directly from chips in PCR, NGS, and RT-PCR assays, demonstrating that high-quality material can be isolated from donor samples using the isolation workflow. Detection of the luminal membrane protein TSG101 with antibodies depended on membrane permeabilization, consistent with the presence of vesicles on the chip. Protein, morphological, and size characterization revealed that these vesicles had the characteristics of EVs. The results demonstrated that unprocessed cfDNA, EV-RNA, and EV-associated proteins can be isolated and simultaneously fluorescently analyzed on the ACE chip. The compatibility with established downstream technologies may also allow the use of the platform as a sample preparation method for workflows that could benefit from access to unprocessed exosomal, genomic, and proteomic biomarkers.

This research aimed to identify the practice level of the first unit teachers to the performance skills, from the point of schools' managers view in Lattakia city, by using notice card. Descriptive method has used to achieve this aimed, the study included (29) managers and (29) teachers from both genders from elementary schools in Lattakia city for (2017/2018) academic year. Questionnaire to the performance skills was provided and included three issues: (planning, implementation and evaluation) and consisted of (46) points, as well as a note card for teachers, contained the same fields. Reached had several results, the most important of which: -The degree of practice of the teachers of the of the first cycle of basic education of performance competencies from the point of view of managers in the city of Lattakia came to a high degree. -The degree of practicing teachers in the first seminar in the city of Lattakia for performance competencies according to note card came to a medium degree. -There are statistically significant differences between the scores of the members of the research sample on the observation card to assess the degree of their exercise of the performance competencies according to the variable of the educational qualification diploma campaign .While there was no statistically significant difference according to variable number of experience. -There was a statistically significant difference between the average grades of principals of basic education schools and the grades of teachers of the first cycle of basic education in Lattakia on the note card on the degree of exercise of competencies in the performance of the answers of managers. The study also made recommendations, including training courses for teachers of basic education before joining the teaching profession, and setting up special workshops for teachers to train them in practice on the performance competencies, which showed the results of the low degree of practice.

The complete removal of glioblastoma brain tumours is impossible to achieve by surgery alone due to the complex finger-like tentacle structure of the tumour cells and their migration away from the bulk of the tumour at the time of surgery; furthermore, despite aggressive chemotherapy and radiotherapy treatments following surgery, tumour cells continue to grow, leading to the death of patients within 15 months after diagnosis. The naturally occurring carnosine dipeptide has previously demonstrated activity against in vitro cultured glioblastoma cells; however, at natural physiological concentrations, its activity is too low to have a significant effect. Towards realising the full oncological potential of carnosine, the dipeptide was embedded within an externally triggered carrier, comprising a novel nano rod-shaped superparamagnetic iron oxide nanoparticle (ca. 86 × 19 × 11 nm) capped with a branched polyethyleneimine, which released the therapeutic agent in the presence of an external magnetic field. The new nano-carrier was characterized using electron microscopy, dynamic light scattering, elemental analysis, and magnetic resonance imaging techniques. In addition to cytotoxicity studies, the carnosine carrier’s effectiveness as a treatment for glioblastoma was screened in vitro using the U87 human glioblastoma astrocytoma cell line. The labile carnosine (100 mM) suppresses both the U87 cells’ proliferation and mobility over 48 h, resulting in significant reduction in migration and potential metastasis. Carnosine was found to be fully released from the carrier using only mild hyperthermia conditions (40 °C), facilitating an achievable clinical application of the slow, sustained-release treatment of glioblastoma brain tumours that demonstrates potential to inhibit post-surgery metastasis with the added benefit of non-invasive monitoring via MRI.

This paper applies a theory of persuasion using the elaboration likelihood model to explain how communication messages from mobile banking services are interpreted by receivers to increase their trust in mobile banking. We explain how users' security and privacy concerns moderate the central route persuasion relationship between argument quality and trust. A questionnaire survey is employed to test a research model. The findings indicate that central and peripheral route persuasion cues enforce users' trust in mobile banking services. Users with strong privacy and security concerns are more likely to rely on the quality of arguments of the messages. Theoretical and practical implications are discussed in the paper. [ABSTRACT FROM AUTHOR]

In laparoscopic minimally invasive surgeries (MIS), high flow medical Carbon Dioxide (CO2) insufflator is employed to supply CO2 gas forming a gas-filled room inside the abdominal cavity with an evident outlook of intramural parts of the body. Three models of high flow medical CO2 insufflator are presented using MATLAB/SIMULINK-Simscape tool. Proportional Integral Derivative (PID) controllers are selected to separately control pressure, flow, and temperature variables of the first two models (PID-P and PID-PQT). Model Predictive Controller (MPC) is another type of controllers that is favored to control these variables simultaneously for the third model (MPC-PQT). Parameters, specified measurements, and compartments were tuned to achieve smooth running of the systems. Tuning of the controllers is considered to boost the simulation of the models and bring forth preferable results of pressure 0.073 bar (≈ 55 mmHg) in the peritoneal cavity for overweighed patients, in addition to maintaining a temperature of 37 °C as time continues. These outcomes with stability and more realistic curvatures are provided in reasonable short-time scales of few seconds, and of less than one second in the case of MPC-PQT model emphasizing the importance of high flow concept for insufflation purposes in the laparoscopic MIS domain. [ABSTRACT FROM AUTHOR]