719 research outputs found
Maintaining customer service in a fast food outlet
In a fast food outlet, a competitive field, customer service is a crucial factor. Customers are very much concerned about customer service and the quality of the food they get. This research is based on quality of service, inventory management, and employee training methods. Qualitative method is used for data collection for this project since it is more communicative and reliable. Data is collected from observations during work time. The store manager was interviewed for more information about inventory management of the store and customer service. This research found that not all the employees are trained for customer service. The inventory is done manually in the store, which is a time-consuming method. Not keeping sufficient stock leads to a shortage of toppings for pizza in the rush time if demand goes high, which may lead to customer complaints. Results of this research show that the standard of customer service and quality of food can be controlled and improved by managing the inventory, employee retention technique, and proper employee training. The research recommends using employee retention techniques and software methods for better inventory management. Keeping safe stocks as per the demand can reduce customer complaints about the quality of food.
Structure of the herpes-simplex virus portal-vertex
Herpesviruses include many important human pathogens such as herpes simplex virus, cytomegalovirus, varicella-zoster virus, and the oncogenic Epstein–Barr virus and Kaposi sarcoma–associated herpesvirus. Herpes virions contain a large icosahedral capsid that has a portal at a unique 5-fold vertex, similar to that seen in the tailed bacteriophages. The portal is a molecular motor through which the viral genome enters the capsid during virion morphogenesis. The genome also exits the capsid through the portal-vertex when it is injected through the nuclear pore into the nucleus of a new host cell to initiate infection. Structural investigations of the herpesvirus portal-vertex have proven challenging, owing to the small size of the tail-like portal-vertex–associated tegument (PVAT) and the presence of the tegument layer that lays between the nucleocapsid and the viral envelope, obscuring the view of the portal-vertex. Here, we show the structure of the herpes simplex virus portal-vertex at subnanometer resolution, solved by electron cryomicroscopy (cryoEM) and single-particle 3D reconstruction. This led to a number of new discoveries, including the presence of two previously unknown portal-associated structures that occupy the sites normally taken by the penton and the Ta triplex. Our data revealed that the PVAT is composed of 10 copies of the C-terminal domain of pUL25, which are uniquely arranged as two tiers of star-shaped density. Our 3D reconstruction of the portal-vertex also shows that one end of the viral genome extends outside the portal in the manner described for some bacteriophages but not previously seen in any eukaryote viruses. Finally, we show that the viral genome is consistently packed in a highly ordered left-handed spool to form concentric shells of DNA. Our data provide new insights into the structure of a molecular machine critical to the biology of an important class of human pathogens
Variation in the organization and subunit composition of the mammalian pyruvate dehydrogenase complex E2/E3BP core assembly
The final version of this article is available at the link below.Crucial to glucose homoeostasis in humans, the hPDC (human pyruvate dehydrogenase complex) is a massive molecular machine comprising multiple copies of three distinct enzymes (E1–E3) and an accessory subunit, E3BP (E3-binding protein). Its icosahedral E2/E3BP 60-meric ‘core’ provides the central structural and mechanistic framework ensuring favourable E1 and E3 positioning and enzyme co-operativity. Current core models indicate either a 48E2+12E3BP or a 40E2+20E3BP subunit composition. In the present study, we demonstrate clear differences in subunit content and organization between the recombinant hPDC core (rhPDC; 40E2+20E3BP), generated under defined conditions where E3BP is produced in excess, and its native bovine (48E2+12E3BP) counterpart. The results of the present study provide a rational basis for resolving apparent differences between previous models, both obtained using rhE2/E3BP core assemblies where no account was taken of relative E2 and E3BP expression levels. Mathematical modelling predicts that an ‘average’ 48E2+12E3BP core arrangement allows maximum flexibility in assembly, while providing the appropriate balance of bound E1 and E3 enzymes for optimal catalytic efficiency and regulatory fine-tuning. We also show that the rhE2/E3BP and bovine E2/E3BP cores bind E3s with a 2:1 stoichiometry, and propose that mammalian PDC comprises a heterogeneous population of assemblies incorporating a network of E3 (and possibly E1) cross-bridges above the core surface.This work was partly supported by EPSRC (under grants GR/R99393/01 and EP/C015452/1)
Filamentous Influenza Viruses
Clinical isolates of influenza virus produce pleomorphic virus particles, including extremely long filamentous virions. In contrast, strains of influenza that have adapted to laboratory growth typically produce only spherical virions. As a result, the filamentous phenotype has been overlooked in most influenza virus research. Recent advances in imaging and improved animal models have highlighted the distinct structure and functional relevance of filamentous virions. In this review we summarise what is currently known about these strikingly elongated virus particles and discuss their possible roles in clinical infections
The architectural complexity of the human PDC core assembly
The mammalian pyruvate dehydrogenase complex (PDC) is a key multi-enzyme assembly linking the glycolytic pathway to the TCA cycle via the specific conversion of pyruvate to acetyl CoA and, as such, is responsible for the maintenance of glucose homeostasis in humans. PDC comprises a central pentagonal dodecahedral core of 60 dihydrolipoamide acetyltransferase (E2) and 12 E3 binding protein (E3BP) subunits. Presently, two conflicting models of PDC (E2+E3BP) core organisation exist: the ‘addition’ (60+12) and ‘substitution’ (48+12) models. In addition to its catalytic role, the multi-domain E2/E3BP core provides the structural framework to which 30 pyruvate decarboxylase (E1) heterotetramers and 6-12 dihydrolipoamide dehydrogenase (E3) homodimers are proposed to bind at maximal occupancy. The formation of specific E2:E1 and E3BP:E3 subcomplexes are characteristic of eukaryotic PDCs and are critical for normal complex function. Despite the availability of limited structural data, the exact subunit organisation and mechanism of operation of the mammalian E2/E3BP core remains unknown.
This thesis describes the large-scale purification of tagged, recombinant human PDC cores, full-length rE2 and rE2/E3BP, truncated E2/E3BP, peripheral rE3 enzyme as well as native E2/E3BP core (bE2/E3BP) purified from bovine heart. The ability to purify large amounts of pure protein has enabled the characterisation of the individual cores as well as the E2/E3BP:E3 complex using a variety of biochemical and biophysical techniques.
Full-length rE2/E3BP, rE2, bE2/E3BP, truncated E2/E3BP (tLi19/tLi30) and rE2/E3BP:E3 were analysed in solution by analytical ultracentrifugation (AUC). While AUC of the cores supported the substitution model of core organisation, the stoichiometry of interaction was determined to be 2:1 (rE2/E3BP:E3). This was further complemented by gel filtration chromatography (GFC) and small angle neutron scattering (SANS), implying the possible existence of a network of E3 ‘cross-bridges’ linking pairs of E3BP molecules across the surface of the E2 core assembly. Low resolution solution structures obtained for rE2/E3BP, bE2/E3BP and tLi19/tLi30 by small angle x-ray scattering (SAXS) and SANS revealed the presence of icosahedral cores with open pentagonal faces favouring the substitution model of core organisation. These solution structures also indicated high structural similarity between the recombinant and native cores, as well as with the crystal structure obtained previously for the truncated bacterial E2 core. In addition, homology modelling and superimpositions of high- and low-resolution structures of the core revealed conservation of the overall pentagonal dodecahedral morphology despite evolutionary diversity. Evidence for the substitution model of core organisation was further substantiated by negative stain EM of the recombinant and bovine E2/E3BP cores.
SANS stoichiometry data indicated the binding of 10 E3 dimers per E2/E3BP core. Although this could correspond to approximately 1:1 stoichiometry between E2/E3BP:E3, subsequent radiolabelling studies suggested possible variation in core subunit composition between the native and recombinant E2/E3BP cores. Therefore, as opposed to the 48E2+12E3BP substitution model based on AUC and SAXS studies with the recombinant E2/E3BP core, rE2/E3BP cores produced in this study indicated a higher level of incorporation of E3BPs with a maximum core composition of 40E2+20E3BP. On the basis of this new finding we have proposed the ‘variable E3BP substitution model’, wherein the number of E3BPs within the core can range from 0 to a maximum of 20, thus resulting in variable populations of E2/E3BP cores. Despite this core variability, the highly controlled regulatory mechanisms in vivo may bias the core composition towards an average of 48E2+12E3BP. However, as the over-expression of the recombinant E2/E3BP core in our study is not as tightly regulated as in vivo, higher number of E3BPs (>12) is observed to be integrated into the core. This new level of architectural complexity and variable subunit composition in mammalian PDC core organisation is likely to have important implications for the catalytic mechanism, overall complex efficiency and tissue-specific regulation by the intrinsic PDC kinases (PDKs) in normal and disease states.
The E2 cores of the PDC family are known to be highly flexible, exhibiting inherent size variability reflective of the ‘breathing’ of the core. Integration of E3BP into the E2 core assembly would then be expected to have significant consequences for the structural assembly, affecting the ‘breathing’ and in turn the function and regulation of the complex. Unfolding studies to assess core stability via circular dichroism (CD) and tryptophan fluorescence revealed lower stability of the rE2/E3BP core as compared to cores composed exclusively of rE2 subunits, thus implying the contribution of E3BP towards core destabilisation. In addition, crosslinking studies indicated weak dimerisation of rE3BP, which may be a key factor promoting core destabilisation. The lower stability of the E2/E3BP core may be of benefit in mammals where sophisticated fine tuning is required to obtain cores with optimal catalytic and regulatory efficiencies.
SAXS solution structures of E2/E3BP cores obtained were unable to locate the exact positions of E3BP within the core. However, SANS in combination with contrast matching of selectively deuterated components as well as cryo-EM, EM tomography and single molecule studies could be used in future for determination of the exact locations of E3BP, and validating the importance of E2/E3BP core organisation and subunit composition for overall PDC function and regulation
Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end
Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process
Design and Validation of Manufacturing Performance Measurement System Using a Case Study
Many manufacturing organizations have used different measures and measurement systems to determine their performance. Yet, one can improve only what one can measure. Performance measurement is indispensable and is a requirement to identify the issue, troubleshoot, and improve the production system. There are various types of performance measurement systems (PMS) presented in the literature and some of them are commonly used, for example, the balanced scorecard. However, there is little experience of performance measurement in research organizations and only 0.5% of publications are related to performance measurement systems. More specifically, the type of research organization referred in this study is established to provide affordable and convenient access to R&D expertise, facilities, and tools to facilitate rapid adoption of advanced manufacturing technologies to enhance the competitiveness of the U.S. workforce. In this research, a review of the existing literature (between 1995 and 2017) is undertaken to determine the building blocks of a PMS to build a conceptual model for designing PMSs. Based on the findings, the following four components were identified as the building blocks of conceptual model for designing PMS: 1) vertical integration, 2) horizontal integration, 3) cause-and-effect relationship, and 4) daily management system reporting framework. Based on the conceptual model a PMS was designed for assessing the throughput of a manufacturing case study identified in a research organization. A simulation model of the manufacturing case study was developed to validate and test the effectiveness and shortcomings of PMS. The conceptual model developed in this research is not limited to research organizations, it can be applied and tested in industries
Using honey to heal diabetic foot ulcers
Diabetic ulcers seem to be arrested in the inflammatory/proliferative stage of the healing process, allowing infection and inflammation to preclude healing. Antibiotic-resistant bacteria have become a major cause of infections, including diabetic foot infections. It is proposed here that the modern developments of an ancient and traditional treatment for wounds, dressing them with honey, provide the solution to the problem of getting diabetic ulcers to move on from the arrested state of healing. Honeys selected to have a high level of antibacterial activity have been shown to be very effective against antibiotic-resistant strains of bacteria in laboratory and clinical studies. The potent anti-inflammatory action of honey is also likely to play an important part in overcoming the impediment to healing that inflammation causes in diabetic ulcers, as is the antioxidant activity of honey. The action of honey in promotion of tissue regeneration through stimulation of angiogenesis and the growth of fibroblasts and epithelial cells, and its insulin-mimetic effect, would also be of benefit in stimulating the healing of diabetic ulcers. The availability of honey-impregnated dressings which conveniently hold honey in place on ulcers has provided a means of rapidly debriding ulcers and removing the bacterial burden so that good healing rates can be achieved with neuropathic ulcers. With ischemic ulcers, where healing cannot occur because of lack of tissue viability, these honey dressings keep the ulcers clean and prevent infection occurring
Comparative study of dinoprostone vaginal pessary versus PGE2 gel in labour induction: a randomised controlled study
Background: Induction of labour is a method of prematurely or artificially stimulating the onset of labour prior to onset of spontaneous labour. Different preparations of prostaglandin are available differing in their effectiveness, side effects, and price. But the most commonly used agent for induction of labour is the shorter acting PGE2 gel. However recently the longer acting PGE2 vaginal pessary has become available. The aim of this study is to compare the efficacy of PGE2 vaginal pessary versus intracervical PGE2 gel in induction of labour.Methods: A total of 170 antenatal patients were included in the study with 85 each group. Group A was given one dose of PGE2 vaginal pessary and group B was given PGE2 gel which was repeated for maximum of 3 doses at 6 hours interval. Patients were examined for cervical ripening, uterine contractions, fetal heart monitoring and complications. Augmentation, labour duration, type of delivery, complications were all noted for both groups.Results: The 56.47% in pessary group and 40% in gel group did not need augmentation which was statistically significant (p=0.029). There was no difference in the mode of delivery between two groups.Conclusions: In my study, comparing PGE2 gel with PGE2 vaginal pessary, there was no significant difference between them in efficacy and complication. The only significant difference noted in my study was reduced need for augmentation of labour in pessary than PGE2 gel
Virilizing Leydig cell tumor of the ovary: from presentation to treatment - a case report
Leydig cell ovarian tumor is a rare sex cord-gonadal stromal tumor which constitutes less than 0.2% of ovarian tumors. As they produce testosterone, virilization is the most common presenting feature. This case report discusses a multiparous, 55 years old, postmenopausal lady who presented with complaints of excessive scalp hair loss and increased facial hair growth since two years. On examination she had androgenic alopecia, increased facial and midline body hair and clitoromegaly. Blood investigations done showed elevated S. testosterone. CT abdomen done showed no pathological lesions in the adrenal glands. MRI done in view of suspicion of Androgen secreting ovarian tumour showed mildly enlarged left ovary measuring 2×1.8 cm with altered signal intensity. She underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Post operatively, histopathological examination was reported as Benign Leydig cell tumour of left ovary.
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