A BRIEF REVIEW ON PROCESS ANALYTICAL TECHNOLOGY (PAT)

Process analytical technology (PAT) has been defined as a mechanism to design, analyze and control pharmaceutical manufacturing processes through measurement of critical process parameters which affect critical quality attributes. PAT checks the quality of raw material attributes both physically and chemically (i.e. at off-line, on-line, in-line). PAT involves a shift from testing the quality of building to the quality of products by testing at several intermediate steps. PAT saves a huge amount of time and money required for sampling and analysis of products. The main goal of PAT is to provide successful tools such as multivariate data analysis and acquisition tools, modern process analyzers or analytical chemistry, endpoint process monitoring, controlling tools and continuous improvement and knowledge improvement tools. In this review attempt has been carried out to explore the concept of PAT, different tools of PAT, goals of PAT, How it Works and Its benefits

Traditional Ethnomedicinal Knowledge Confined to the Pawra Tribe of Satpura Hills, Maharashtra, India

Ethnobotanical surveys can potentially bring out many different clues for the development of safe, effective and inexpensive indigenous remedies. Present study has been focussed on Pawra tribe of Nandurbar district of Maharashtra, India. Field surveys of this area were carried out during 2000–2005 through several field visits and interviews. The aim of the present study was primarily to evaluate and inverntorize medicinal uses of the plants known to Pawras and to encourage preservation of their culture, conservation and sustainable utilization of the plant wealth. After an extensive comparison with literature, about 80 unique or less known uses of 79 plant species belonging to 59 families are described. The documented ethnomedicinal usage of plants mostly pertains to cure asthma, inflammation, lactation, menstrual problems, poisonous bites, skin problems, stomach ache and tooth ache. We found that the study area is rich in ethnic and biodiversity and the tribe posses a valuable treasure of ethnobotanical knowledge. This wisdom available with the tribe is transmitted only through oral communication in locally-spoken, script-less language and therefore needs conservation. The plants used by the Pawra tribe are arranged alphabetically followed by family name, herbarium number, local name, parts used, mode of preparation and medicinal uses

Iron-sparing Response of Mycobacterium avium subsp. paratuberculosis is strain dependent

<p>Abstract</p> <p>Background</p> <p>Two genotypically and microbiologically distinct strains of <it>Mycobacterium avium </it>subsp. <it>paratuberculosis </it>(MAP) exist - S and C MAP strains that primarily infect sheep and cattle, respectively. Concentration of iron in the cultivation medium has been suggested as one contributing factor for the observed microbiologic differences. We recently demonstrated that S strains have defective iron storage systems, leading us to propose that these strains might experience iron toxicity when excess iron is provided in the medium. To test this hypothesis, we carried out transcriptional and proteomic profiling of these MAP strains under iron-replete or -deplete conditions.</p> <p>Results</p> <p>We first complemented <it>M. smegmatis</it>Δ<it>ideR </it>with IdeR of C MAP or that derived from S MAP and compared their transcription profiles using <it>M. smegmatis mc</it>^<it>2</it><it>155 </it>microarrays. In the presence of iron, sIdeR repressed expression of <it>bfrA </it>and MAP2073c, a ferritin domain containing protein suggesting that transcriptional control of iron storage may be defective in S strain. We next performed transcriptional and proteomic profiling of the two strain types of MAP under iron-deplete and -replete conditions. Under iron-replete conditions, C strain upregulated iron storage (BfrA), virulence associated (Esx-5 and antigen85 complex), and ribosomal proteins. In striking contrast, S strain downregulated these proteins under iron-replete conditions. iTRAQ (isobaric tag for relative and absolute quantitation) based protein quantitation resulted in the identification of four unannotated proteins. Two of these were upregulated by a C MAP strain in response to iron supplementation. The iron-sparing response to iron limitation was unique to the C strain as evidenced by repression of non-essential iron utilization enzymes (aconitase and succinate dehydrogenase) and upregulation of proteins of essential function (iron transport, [Fe-S] cluster biogenesis and cell division).</p> <p>Conclusions</p> <p>Taken together, our study revealed that C and S strains of MAP utilize divergent metabolic pathways to accommodate in vitro iron stress. The knowledge of the metabolic pathways these divergent responses play a role in are important to 1) advance our ability to culture the two different strains of MAP efficiently, 2) aid in diagnosis and control of Johne's disease, and 3) advance our understanding of MAP virulence.</p

Assessment of bioaccumulation potential of mangroves along the coast of Maharashtra, India using statistical indices

1372-1378Mangroves are a group of plants growing in estuarine region. These species survive well in saline environment with some adaptations in them. The members of family Avicenniaceae and Sonneratiaceae are of accumulating in nature and may bio-accumulate the pollutants from sediments and water. In order to improve the comprehensive understanding of heavy metal tolerance, the sediments and plant material (leaves) of mangroves were analyzed for heavy metals concentration from different creeks and estuaries of Maharashtra coast using atomic absorption spectrophotometer. The mangrove sediments were analyzed for indices such as enrichment factor, pollution load index, geo-accumulation index etc. to understand the level of pollutants. The bioaccumulation factor was also estimated to understand the bioaccumulation potential mangrove species i.e. Avicennia marina and Sonneratia apetala. The former species is commonly known as pollution tolerate, while the latter is pioneer in mangrove succession. The objectives of the study were to understand the potential of S. apetala in phytoremediation of heavy metals from both sediments and waste water. The mangrove sites like Kandalwada and Uran are on the borderline of pollution and needs proper protection and management

A KLK6 activity-based probe reveals a role for KLK6 activity in pancreatic cancer cell invasion

Pancreatic cancer has the lowest survival rate of all common cancers due to late diagnosis and limited treatment options. Serine hydrolases are known to mediate cancer progression and metastasis through initiation of signaling cascades and cleavage of extracellular matrix proteins, and the kallikrein-related peptidase (KLK) family of secreted serine proteases have emerging roles in pancreatic ductal adenocarcinoma (PDAC). However, the lack of reliable activity-based probes (ABPs) to profile KLK activity has hindered progress in validation of these enzymes as potential targets or biomarkers. Here, we developed potent and selective ABPs for KLK6 by using a positional scanning combinatorial substrate library and characterized their binding mode and interactions by X-ray crystallography. The optimized KLK6 probe IMP-2352 (kobs/I = 11,000 M–1 s–1) enabled selective detection of KLK6 activity in a variety of PDAC cell lines, and we observed that KLK6 inhibition reduced the invasiveness of PDAC cells that secrete active KLK6. KLK6 inhibitors were combined with N-terminomics to identify potential secreted protein substrates of KLK6 in PDAC cells, providing insights into KLK6-mediated invasion pathways. These novel KLK6 ABPs offer a toolset to validate KLK6 and associated signaling partners as targets or biomarkers across a range of diseases

Sterically shielded spin labels for in-cell EPR spectroscopy: Analysis of stability in reducing environment

Post-print (lokagerð höfundar)Electron paramagnetic resonance (EPR) spectroscopy is a powerful and widely used technique for studying structure and dynamics of biomolecules under bio-orthogonal conditions. In-cell EPR is an emerging area in this field; however, it is hampered by the reducing environment present in cells, which reduces most nitroxide spin labels to their corresponding diamagnetic N-hydroxyl derivatives. To determine which radicals are best suited for in-cell EPR studies, we systematically studied the effects of substitution on radical stability using five different classes of radicals, specifically piperidine-, imidazolidine-, pyrrolidine-, and isoindoline-based nitroxides as well as the Finland trityl radical. Thermodynamic parameters of nitroxide reduction were determined by cyclic voltammetry; the rate of reduction in the presence of ascorbate, cellular extracts, and after injection into oocytes was measured by continuous-wave EPR spectroscopy. Our study revealed that tetraethyl-substituted nitroxides are good candidates for in-cell EPR studies, in particular pyrrolidine derivatives, which are slightly more stable than the trityl radical.This work was supported by the Icelandic Research Fund (120001021), the Deutsche Forschungsgemeinschaft (SFB 902, Molecular principles of RNA-based regulation) and by a doctoral fellowship to A. P. Jagtap from the University of Iceland Research Fund.Peer reviewe

X-ray and MR contrast bearing nanoparticles enhance the therapeutic response of image-guided radiation therapy for oral cancer

INTRODUCTION: Radiation therapy for head and neck squamous cell carcinoma is constrained by radiotoxicity to normal tissue. We demonstrate 100 nm theranostic nanoparticles for image-guided radiation therapy planning and enhancement in rat head and neck squamous cell carcinoma models. METHODS: PEG conjugated theranostic nanoparticles comprising of Au nanorods coated with Gadolinium oxide layers were tested for radiation therapy enhancement in 2D cultures of OSC-19-GFP-luc cells, and orthotopic tongue xenografts in male immunocompromised Salt sensitive or SS rats via both intratumoral and intravenous delivery. The radiation therapy enhancement mechanism was investigated. RESULTS: Theranostic nanoparticles demonstrated both X-ray/magnetic resonance contrast in a dose-dependent manner. Magnetic resonance images depicted optimal tumor-to-background uptake at 4 h post injection. Theranostic nanoparticle + Radiation treated rats experienced reduced tumor growth compared to controls, and reduction in lung metastasis. CONCLUSIONS: Theranostic nanoparticles enable preprocedure radiotherapy planning, as well as enhance radiation treatment efficacy for head and neck tumors

Design of Product Service Systems at the Base of The Pyramid

Abstract in UndeterminedThe Base of the Pyramid (BoP) consists of about two-fifths of the world population. This population can be categorized as poor with income of less than 2 dollars per day. It is important to alleviate poverty. One of the promising approaches to tackle the wicked problem of poverty is business development combined with poverty alleviation. In this approach, integrated solutions are necessary in order to address the diverse issues in the BoP. These integrated solutions are in the form of product service systems (PSS) rather than the conventional product-oriented or service-oriented solutions. In this paper, we explore different issues that need to be addressed in the PSS design at the BoP. We have also explored strategies used in this PSS design. We have used a case study to explain these issues and strategies. In addition, we have identified salient characteristics of the PSS design at the BoP

Constructing Fluorogenic Bacillus Spores (F-Spores) via Hydrophobic Decoration of Coat Proteins

Background: Bacterial spores are protected by a coat consisting of about 60 different proteins assembled as a biochemically complex structure with intriguing morphological and mechanical properties. Historically, the coat has been considered a static structure providing rigidity and mainly acting as a sieve to exclude exogenous large toxic molecules, such as lytic enzymes. Over recent years, however, new information about the coat’s architecture and function have emerged from experiments using innovative tools such as automated scanning microscopy, and high resolution atomic force microscopy. Principal Findings: Using thin-section electron microscopy, we found that the coat of Bacillus spores has topologically specific proteins forming a layer that is identifiable because it spontaneously becomes decorated with hydrophobic fluorogenic probes from the milieu. Moreover, spores with decorated coat proteins (termed F-spores) have the unexpected attribute of responding to external germination signals by generating intense fluorescence. Fluorescence data from diverse experimental designs, including F-spores constructed from five different Bacilli species, indicated that the fluorogenic ability of F-spores is under control of a putative germination-dependent mechanism. Conclusions: This work uncovers a novel attribute of spore-coat proteins that we exploited to decorate a specific layer imparting germination-dependent fluorogenicity to F-spores. We expect that F-spores will provide a model system to gai