Developing Framework for the Implementation of Advanced Manufacturing Technologies in Small and Medium-Sized Enterprises

Intense competition, demanding customers, and shortening product life cycles are prompting small- and medium-sized enterprises to invest in advanced manufacturing technologies (AMTs). Small manufacturers often depend on large manufacturers for orders and so require design as well as manufacturing flexibility on their part. One way of achieving the flexibility is through adoption of AMTs. The decision to invest in AMT is a major decision and thus requires proper consideration to all the aspects of the implementation process before a final commitment is made. Although the technical capabilities of AMTs are well proven, neither practitioner nor academics agree upon a framework for its successful implementation. Using Churchill’s model (Steps 1 and 2) and drawing a link from the available literature, a theoretical framework is developed for the successful implementation of AMTs in small- and medium-sized enterprises. Three implementation phases—namely, planning, preimplementation, and postimplementation—with 14 major issues have been developed; 52 constituent factors have been identified from these issues through literature review and interviews with industry professionals

Antioxidant and antimicrobial activities of Heracleum nepalense D Don root

Purpose: The aim of the present study was to investigate antioxidant and antimicrobial effects of the methanol extract of Heracleum nepalense D.Don roots. Method: The antimicrobial effect was determined by agar dilution and disc diffusion method. The free radical scavenging potential was studied by using different antioxidants models of screening using vitamin E (5mM) as standard. Results: The crude methanol extract of H.nepalense root was found to be active against both Gram-positive and Gram-negative organisms. The ethyl acetate soluble fraction of the extract showed similar activity against these organisms. Similarly, the methanol extract at 1000 mg. ml-1 and the ethyl acetate fraction at 50 mg. ml-1 exhibited significant antioxidant activity in ferrous sulphate induced lipid peroxidation, 1,1- diphenyl- 2-picryl hydrazyl (DPPH), Hydroxyl radical and Superoxide scavenging models. Conclusions: The study confirms the possible antioxidant and antimicrobial potentiality of the plant extract. Presence of flavonoid alone or in combination with its other components could be responsible for the activity. Keywords: Heracleum nepalense, Lipid peroxidation, Superoxide scavenging, DPPH assay, Antimicrobial effect, Flavonoid> Tropical Journal of Pharmaceutical Research Vol. 4 (1) 2005: pp. 341-34

Borderline Ovarian Malignancies : A Single Institute Retrospective Study.

Background: Borderline ovarian tumors are histologically characterized as epithelial tumors with a stratified growth pattern but without destructive stromal invasion. Little is known about the histological subtypes and outcome, role of fertility sparing surgery and role of postoperative therapy in advanced stage in Indian scenario. While there is ample data in the world literature about this disease, prognosis in Indian patients is largely unknown due to dearth of studies in our setting. Objective: To study the demographic profile, clinical features, imaging, treatment and outcome of borderline ovarian tumors. Methods: This is a retrospective study of eighty seven patients with pathologically proven diagnosis of borderline ovarian tumor, diagnosed and treated from January 2006 to October 2011 at our institution. Most patients underwent surgical staging which incuded total abdominal hysterectomy and bilateral salphingo-oophorectomy, infracolic omentectomy, bilateral pelvic and para aortic lymphadenectomy. Young patients who had not completed their family underwent fertility sparing surgery. Patients with invasive metastatic implants received adjuvant chemotherapy. The outcome of these patients was correlated with stage, type of peritoneal implant, type of surgical procedure and with histological subtype. Results: At a median follow-up of 48 months, 100 percent survival was noted. One patient with stage III disease had recurrence. Conclusions: Borderline ovarian tumors occur at a younger age compared to invasive tumors. In patients with early stage disease who wish to preserve fertility, hysterectomy and contralateral oophorectomy are not necessary. Serous tumors occur at a younger age. They can be associated with invasive peritoneal implants and raised CA125 values. Majority of the serous tumors are bilateral and smaller in size compared to mucinous and endometroid tumors. Raised CA125 values did not correlate with the stage of disease. These patients have an excellent prognosis even in Indian scenario where majority of patients present with big ovarian masses

ANTIOXIDANT ACTIVITY OF POMEGRANATE PEEL POWDER

The aim of present study was to evaluate in-vitro anti-oxidant properties of Punica granatum fruit (Pomegranate fruit) peel. Antioxidants are molecules involved in defense mechanisms against the deleterious effects of free radicals in most organisms. Antioxidants are the agents responsible for scavenging free radicals. A number of methods are currently being used for the evaluation of the antioxidant and free-radical scavenging properties of natural and synthetic antioxidants, including the DPPH method. The Punica granatum fruit (Pomegranate fruit) peel powder suspension was prepared and the DPPH radical scavenging assay was the method adopted to determine antioxidant potentials of aqueous suspension of pomegranate peel powder. Results revealed that DPPH aqueous solution gave comparable free-radical activity 24 hours post preparation compared with the freshly prepared solution. After 24 hours, activity was greatly reduced. It is, therefore, recommended that freshly prepared DPPH solution should be used at all times; however for prolonged experimental schedules, the DPPH solution should be used within 24 hours post preparation, so as to give comparable results with the freshly prepared solution and avoid ambiguity in results interpretation. Aqueous suspension of peel powder showed good antioxidant effect. Phenolic compounds, tannins and flavonoids are the major phytochemicals present in the pomegranate peel. Percentage of inhibition increased with the increased concentration of extracts. The present study provides evidence that the Punica granatum fruit peels is potential source of natural antioxidant Keywords: Antioxidant, Pomegranate peel powder suspension, DPPH, Free radical scavenging

A Secure Storage Management & Auditing Scheme for Cloud Storage

Cloud computing is an evolving domain that provides many on-demand services that are used by many businesses on daily basis. Massive growth in cloud storage results in new data centers which are hosted by a large number of servers. As number of data centers increases enormous amount of energy consumption also increases. Now cloud service providers are looking for environmental friendly alternatives to reduce energy consumption. Data storage requires huge amount of resources and management. Due to increasing amount of demand for data storage new frameworks needed to store and manage data at a low cost. Also to prevent data from unauthorized access cloud service provider must provide data access control. Data access control is an effective way to ensure data storage security within cloud. For data storage cost minimization we are using DCT compression technique to ensure data compression without compromising the quality of the data. For data access control and security asymmetric cryptographic algorithm RSA is used. For data auditing we have used MD5 with RSA to generate digital signatures, In proposed work we tried to cover all attributes in terms of efficiency, performance and security in cloud computing

FORMULATION, DEVELOPMENT AND CHARACTERIZATION OF SOLID LIPID NANOPARTICLES OF GEMCITABINE HYDROCHLORIDE

Gemcitabine Hydrochloride is a BCS class III drug of choice in the treatment of cancer, as a single or in combination chemotherapy. However, its bioavailability is a major concern due to its short half-life. Solid lipid nanoparticles (SLN) of Gemcitabine Hydrochloride were prepared to enhance its bioavailability, hence anticancer activity. The Quality by Design approach was applied for the formulation of SLN. The Randomized 32 factorial design was used with responses of particle size and % entrapment efficiency (% EE). The optimized batch of Gemcitabine Hydrochloride loaded SLN containing 1gm of GMS as solid lipid, 1gm of Tween80: Sodium Taurocholate as surfactant:co-surfactant and 5mg of Gemcitabine Hydrochloride was prepared by high shear homogenization method followed by Probe sonication for 15min to form nanoparticulate SLN dispersion. The Optimized batch of Gemcitabine Hydrochloride loaded SLN that exhausted mean particle size of 126.1nm, zeta potential -28.6 mV and % EE 74.83% respectively. SEM studies revealed three-dimensional nature of SLN with a slightly rough surface. DSC, results exhibited entrapment of Gemcitabine Hydrochloride in SLN. The optimized batch of SLN was evaluated for in-vitro % drug release using cellulose membrane dialysis bags for 24hrs and showed 63.13% CDR at 24 hrs. Anticancer cell line studies were also performed in human lung cancer cell line (A-549). It concludes that Gemcitabine Hydrochloride loaded Solid lipid Nanoparticles was successfully formulated and evaluated to sustain the drug release by bypassing the first pass metabolism. Key words: Gemcitabine Hydrochloride, SLN, QbD, High shear homogenization, anticancer activity.Â

Cellular Metabolomics Profiles Associated With Drug Chemosensitivity in AML

BackgroundAcute myeloid leukemia (AML) is a hematological malignancy with a dismal prognosis. For over four decades, AML has primarily been treated by cytarabine combined with an anthracycline. Although a significant proportion of patients achieve remission with this regimen, roughly 40% of children and 70% of adults relapse. Over 90% of patients with resistant or relapsed AML die within 3 years. Thus, relapsed and resistant disease following treatment with standard therapy are the most common clinical failures that occur in treating this disease. In this study, we evaluated the relationship between AML cell line global metabolomes and variation in chemosensitivity.MethodsWe performed global metabolomics on seven AML cell lines with varying chemosensitivity to cytarabine and the anthracycline doxorubicin (MV4.11, KG-1, HL-60, Kasumi-1, AML-193, ME1, THP-1) using ultra-high performance liquid chromatography – mass spectrometry (UHPLC-MS). Univariate and multivariate analyses were performed on the metabolite peak intensity values from UHPLC-MS using MetaboAnalyst to identify cellular metabolites associated with drug chemosensitivity.ResultsA total of 1,624 metabolic features were detected across the leukemic cell lines. Of these, 187 were annotated to known metabolites. With respect to doxorubicin, we observed significantly greater abundance of a carboxylic acid (1-aminocyclopropane-1-carboxylate) and several amino acids in resistant cell lines. Pathway analysis found enrichment of several amino acid biosynthesis and metabolic pathways. For cytarabine resistance, nine annotated metabolites were significantly different in resistance vs. sensitive cell lines, including D-raffinose, guanosine, inosine, guanine, aldopentose, two xenobiotics (allopurinol and 4-hydroxy-L-phenylglycine) and glucosamine/mannosamine. Pathway analysis associated these metabolites with the purine metabolic pathway.ConclusionOverall, our results demonstrate that metabolomics differences contribute toward drug resistance. In addition, it could potentially identify predictive biomarkers for chemosensitivity to various anti-leukemic drugs. Our results provide opportunity to further explore these metabolites in patient samples for association with clinical response

Poly(β-Amino Ester)-Nanoparticle Mediated Transfection of Retinal Pigment Epithelial Cells In Vitro and In Vivo

A variety of genetic diseases in the retina, including retinitis pigmentosa and leber congenital amaurosis, might be excellent targets for gene delivery as treatment. A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Poly(beta-amino ester)s (PBAEs) have shown great potential as gene delivery reagents because they are easily synthesized and they transfect a wide variety of cell types with high efficacy in vitro. We synthesized a combinatorial library of PBAEs and evaluated them for transfection efficacy and toxicity in retinal pigment epithelial (ARPE-19) cells to identify lead polymer structures and transfection formulations. Our optimal polymer (B5-S5-E7 at 60 w/w polymer∶DNA ratio) transfected ARPE-19 cells with 44±5% transfection efficacy, significantly higher than with optimized formulations of leading commercially available reagents Lipofectamine 2000 (26±7%) and X-tremeGENE HP DNA (22±6%); (p<0.001 for both). Ten formulations exceeded 30% transfection efficacy. This high non-viral efficacy was achieved with comparable cytotoxicity (23±6%) to controls; optimized formulations of Lipofectamine 2000 and X-tremeGENE HP DNA showed 15±3% and 32±9% toxicity respectively (p>0.05 for both). Our optimal polymer was also significantly better than a gold standard polymeric transfection reagent, branched 25 kDa polyethyleneimine (PEI), which achieved only 8±1% transfection efficacy with 25±6% cytotoxicity. Subretinal injections using lyophilized GFP-PBAE nanoparticles resulted in 1.1±1×103-fold and 1.5±0.7×103-fold increased GFP expression in the retinal pigment epithelium (RPE)/choroid and neural retina respectively, compared to injection of DNA alone (p = 0.003 for RPE/choroid, p<0.001 for neural retina). The successful transfection of the RPE in vivo suggests that these nanoparticles could be used to study a number of genetic diseases in the laboratory with the potential to treat debilitating eye diseases

Optimized Hydrophobic Interactions and Hydrogen Bonding at the Target-Ligand Interface Leads the Pathways of Drug-Designing

Weak intermolecular interactions such as hydrogen bonding and hydrophobic interactions are key players in stabilizing energetically-favored ligands, in an open conformational environment of protein structures. However, it is still poorly understood how the binding parameters associated with these interactions facilitate a drug-lead to recognize a specific target and improve drugs efficacy. To understand this, comprehensive analysis of hydrophobic interactions, hydrogen bonding and binding affinity have been analyzed at the interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d] pyrimidine compounds.In-silico docking studies were performed, using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to investigate the role of ligand binding affinity at the hydrophobic pocket of c-Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA calculations were scrutinized to quantify the role of weak interactions in binding affinity and drug efficacy.The in-silico method has enabled us to reveal that a multi-targeted small molecule binds with low affinity to its respective targets. But its binding affinity can be altered by integrating the conformationally favored functional groups at the active site of the ligand-target interface. Docking studies of 4-amino-substituted molecules at the bioactive cascade of the c-Src and c-Abl have concluded that 3D structural folding at the protein-ligand groove is also a hallmark for molecular recognition of multi-targeted compounds and for predicting their biological activity. The results presented here demonstrate that hydrogen bonding and optimized hydrophobic interactions both stabilize the ligands at the target site, and help alter binding affinity and drug efficacy

Red flags for the early detection of spinal infection in back pain patients

© 2019 The Author(s). Background: Red flags are signs and symptoms that are possible indicators of serious spinal pathology. There is limited evidence or guidance on how red flags should be used in practice. Due to the lack of robust evidence for many red flags their use has been questioned. The aim was to conduct a systematic review specifically reporting on studies that evaluated the diagnostic accuracy of red flags for Spinal Infection in patients with low back pain. Methods: Searches were carried out to identify the literature from inception to March 2019. The databases searched were Medline, CINHAL Plus, Web of Science, Embase, Cochrane, Pedro, OpenGrey and Grey Literature Report. Two reviewers screened article texts, one reviewer extracted data and details of each study, a second reviewer independently checked a random sample of the data extracted. Results: Forty papers met the eligibility criteria. A total of 2224 cases of spinal infection were identified, of which 1385 (62%) were men and 773 (38%) were women mean age of 55 (± 8) years. In total there were 46 items, 23 determinants and 23 clinical features. Spinal pain (72%) and fever (55%) were the most common clinical features, Diabetes (18%) and IV drug use (9%) were the most occurring determinants. MRI was the most used radiological test and Staphylococcus aureus (27%), Mycobacterium tuberculosis (12%) were the most common microorganisms detected in cases. Conclusion: The current evidence surrounding red flags for spinal infection remains small, it was not possible to assess the diagnostic accuracy of red flags for spinal infection, as such, a descriptive review reporting the characteristics of those presenting with spinal infection was carried out. In our review, spinal infection was common in those who had conditions associated with immunosuppression. Additionally, the most frequently reported clinical feature was the classic triad of spinal pain, fever and neurological dysfunction. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/