1,272 research outputs found

    Synthetic (p)ppGpp analogue is an inhibitor of stringent response in mycobacteria

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    Bacteria elicit an adaptive response against hostile conditions such as starvation and other kinds of stresses. Their ability to survive such conditions depends, in part, on stringent response pathways. (p)ppGpp, considered to be the master regulator of the stringent response, is a novel target for inhibiting the survival of bacteria. In mycobacteria, the (p)ppGpp synthetase activity of bifunctional Rel is critical for stress response and persistence inside a host. Our aim was to design an inhibitor of (p)ppGpp synthesis, monitor its efficiency using enzyme kinetics, and assess its phenotypic effects in mycobacteria. As such, new sets of inhibitors targeting (p)ppGpp synthesis were synthesized and characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. We observed significant inhibition of (p)ppGpp synthesis by Rel(Msm) in the presence of designed inhibitors in a dose-dependent manner, which we further confirmed by monitoring the enzyme kinetics. The Rel enzyme inhibitor binding kinetics were investigated by isothermal titration calorimetry. Subsequently, the effects of the compounds on long-term persistence, biofilm formation, and biofilm disruption were assayed in Mycobacterium smegmatis, where inhibition in each case was observed. In vivo, (p)ppGpp levels were found to be downregulated in M. smegmatis treated with the synthetic inhibitors. The compounds reported here also inhibited biofilm formation by the pathogen Mycobacterium tuberculosis. The compounds were tested for toxicity by using an MTT assay with H460 cells and a hemolysis assay with human red blood cells, for which they were found to be nontoxic. The permeability of compounds across the cell membrane of human lung epithelial cells was also confirmed by mass spectrometry

    Synthesis of Substituted 2-Amino-Cyclobutanones

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    A series of weakly nucleophilic nitrogen derivatives including carbamates, amides, sulfonamides, and anilines were reacted with 1,2‐bis(trimethylsilyloxy)cyclobutene under acidic conditions to afford various substituted 2‐aminocyclobutanone derivatives 3a–i in modest to excellent yields

    DEVELOPMENT OF A LAGRANGIAN-LAGRANGIAN METHODOLOGY TO PREDICT BROWNOUT DUST CLOUDS

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    A Lagrangian-Lagrangian dust cloud simulation methodology has been developed to help better understand the complicated two-phase nature of the rotorcraft brownout problem. Brownout conditions occur when rotorcraft land or take off from ground surfaces covered with loose sediment such as sand and dust, which decreases the pilot's visibility of the ground and poses a serious safety of flight risk. The present work involved the development of a comprehensive, computationally efficient three-dimensional sediment tracking method for dilute, low Reynolds number Stokes-type flows. The flow field generated by a helicopter rotor in ground effect operations over a mobile sediment bed was modeled by using an inviscid, incompressible, Lagrangian free-vortex method, coupled to a viscous semi-empirical approximation for the boundary layer flow near the ground. A new threshold model for the onset of sediment mobility was developed by including the effects of unsteady pressure forces that are induced in vortically dominated rotor flows, which can significantly alter the threshold conditions for particle motion. Other important aspects of particle mobility and uplift in such vortically driven dust flows were also modeled, including bombardment effects when previously suspended particles impact the bed and eject new particles. Bombardment effects were shown to be a particularly significant contributor to the mobilization and eventual suspension of large quantities of smaller-sized dust particles, which tend to remain suspended. A numerically efficient Lagrangian particle tracking methodology was developed where individual particle or clusters of particles were tracked in the flow. To this end, a multi-step, second-order accurate time-marching scheme was developed to solve the numerically stiff equations that govern the dynamics of particle motion. The stability and accuracy of this scheme was examined and matched to the characteristics of free-vortex method. One-way coupling of the flow and the particle motion was assumed. Particle collisions were not considered. To help reduce numerical costs, the methodology was implemented on graphic processing units, which gave over an order of magnitude reduction in simulation time without any loss in accuracy. Validation of the methodology was performed against available measurements, including flow field measurements that have been made with laboratory-scale and full-scale rotors in ground effect operations. The predicted dust clouds were also compared against measurements of developing dust clouds produced by a helicopter during taxi-pass and approach-to-touchdown flight maneuvers. The results showed that the problem of brownout is mostly driven by the local action of the rotor wake vortices and the grouping or bundling of vortex filaments near the sediment bed. The possibilities of mitigating the intensity of brownout conditions by diffusing the blade tip vortices was also explored. While other means of brownout mitigation may be possible, enhancing the diffusion of the tip vortices was shown to drastically reduce the quantity of mobilized particles and the overall severity of the brownout dust cloud

    Content Analysis of the Excellence of Employee Performance: a Study of the Employer branding Models

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    Purpose – Review of literature provides number of models highlighting the perception of potential employees in context with employer branding. However, these models lack empirical investigation in different industries like insurance, tourism & travel, hospitality and banks. These frameworks have highlighted the perception of employers towards positioning their organisation image in the mind of potential employees.Six Online databases, namely, Emerald, JSTOR, Sage Publications, Science Direct, Springer Link and Taylor & Francis have been surfed to list the articles with title “Employer Branding” or with the title “Employer Attractiveness” and the total listed articles from databases of Taylor & Francis, Emerald, Springer Link, JSTOR, Science Direct and Sage Publications respectively have been thoroughly reviewed. The majority of studies on “Employer Branding” and on “Employer Attractiveness” have been carried out in different countries of the world that is in US, UK, China, Portugal, Netherlands, and in different service industries like hotels, banking, aviation and telecom sector. In theoretical terms, the researchers have remarked in their studies that employer branding terminology can be a strong basis for attracting the new talent and prospective candidate for the right job at right time in right place in various service industries. However, the focus has to be shifted in studying the employer branding terminology from current employee perspective.The study has provided basis for applying the models in different industries with the theoretical support. Future research should seek to give empirical evidence regarding the congruence between employer branding and employee performance. The conceptualized models can also be empirical investigated and may be employed in different industries to study the influence of various parameters on the service employees. The results from review of literature presented here should lead analysts to recognize that measuring and strategically managing employer branding may in fact become the most important managerial activity for driving organizational performance among current employees.The paper discusses the similarity and differences in the two models by [1]on employer branding from the perception of current employees towards their present organisation. The study provides a unique opportunity to understand the two models and their applicability in the banking industry. Moreover, these two models and its various perspectives were found to be more suitable and apt for the banking industry

    Impact on Employee Satisfaction, Brand Commitment and Employee Turnover- Role of Employer Branding

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    The results of the study have indicated that in order to secure the lifelong success of any banking institution the retention of key bank employees have been critical factor to be taken into consideration. It has been observed that it is more profitable for organizations to have good and attractive brand name, which reflects employees’ perception of employer and their beliefs and values about the bank. By providing employees with social security, economic stability and career development, they will be more satisfied, more committed towards keeping the brand name and are less likely to leave for another banks. Therefore, it becomes necessary for the bank employers to keep their employees happy and contended in the bank culture by providing them an attractive work environmen

    Cook Off Study of Combustible Cartridge Cases

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    Combustible cartridge case (CCC) offers specific advantages over the conventional metallic (brass) case. The CCCs are made of cellulose fibres with suitable explosives to ensure debris-free combustion inside the gun barrel. The presence of explosives in CCC, however, causes increased vulnerability to cook-off. An experimental study of cook-off of CCC was carried out by hot plate technique. Cook-off data for CCC of different compositions and with various cook-off delay coatings was measured. It was found that out of four types of coatings, two gave better results

    Editors’ Note

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    This year, we are very excited to announce the second issue of the Bone Bulletin, DePalma Orthopaedic Society’s student-run, non-peer reviewed journal for Sidney Kimmel Medical College (SKMC) students. The journal was initially started to provide another way to become involved with orthopaedics in medical school as well as providing a unique platform to report on diverse aspects of the field through editorial and opinion pieces. By providing close 1-on-1 mentorship with a Rothman physician, the Bone Bulletin gives students a hands-on opportunity to engage with orthopaedic research and developments. Throughout this journal, you will find a variety of research articles, clinical insights, and thought-provoking reviews related to the field of orthopaedics. We believe that this journal provides students the ability to express their ideas in a creative fashion with the goal of advancing the field of orthopaedic surgery. We extend our gratitude to the writers and editorial team, who have formed the contributions featured in this issue. We would also like to express our gratitude to the mentors and physicians from the Rothman Orthopaedic Institute, who have supported us throughout this journey. Your guidance, encouragement, and expertise have been invaluable in shaping this endeavor and inspiring us to pursue excellence in the field of orthopaedics. Thank you for joining us again this year. We are beyond excited to present the invaluable contributions that everyone has made for the Bone Bulletin to come to fruition for another year. Sincerely,Ari Clements & Amit SyalEditors-in-Chief, The Bone Bulleti

    Study of Brass Obturator Design for Combustible Cartridge Case for 105mm Tank Gun Ammunition

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    Brass cartridge case provides rearward obturation in the tank gun ammunition where the gun systedt has a sliding breech mechanism. In the case of semi-combustible cartridge case (SCCC) ammunition, obturation is provided by a smal1 metal stub. The mechanism of obturation and obturator design for kinetic energy and high explosive squash heat (HESH), SCCC ammunition of 105mm tank gun have been studied. The dynamic firing results for SCCC ammunition for 105 mm tank gun reveal height 115 mm provides perfect obturation. The ballistic performance of SCCC ammunition is comparable with that of the brass-cartridged round in the pressure range 150-450 MPa
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