425 research outputs found

    Crystallisation of active pharmaceutical ingredients using ionic liquids

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    It is proposed that Ionic Liquids offer a new opportunity for exploration into a novel medium for processing Active Pharmaceutical Ingredients, particularly with respect to habit control and polymorphic form. A review of relevant literature relating to ionic liquids properties, commercial applications and current research has been summarised together with background into fundamental crystallisation theory. Crystallisations using thermal methods were employed at laboratory scale and the physical properties of the resultant powders were analysed and compared to commonly encountered crystal forms. For paracetamol it was found that the morphology of the crystals could be manipulated, producing in some cases, habits not reported for conventional organic solvent crystallisation. This was achieved through changing both the IL used and the saturation of the system whilst in all cases retaining the most stable polymorph. ILs ILs to be ‘designed’ for a given API but greater understanding of the interactions between IL and solute are required first. Properties such as increased solvation power, thermal stability, liquidus range and low vapour pressure bring a number of advantages when designing industrial crystallisations. However ILs also have a number of disadvantages including phase separation problems

    Epigenetics Underpinning the Regulation of the CXC (ELR+) Chemokines in Non-Small Cell Lung Cancer

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    Background: Angiogenesis may play a role in the pathogenesis of Non-Small Cell Lung cancer (NSCLC). The CXC (ELR+) chemokine family are powerful promoters of the angiogenic response. Methods: The expression of the CXC (ELR+) family members (CXCL1-3/GROα-γ, CXCL8/IL-8, CXCR1/2) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of these chemokines was examined in normal bronchial epithelial and NSCLC cell lines. Results: Overall, expression of the chemokine ligands (CXCL1, 2, 8) and their receptors (CXCR1/2) were down regulated in tumour samples compared with normal, with the exception of CXCL3. CXCL8 and CXCR1/2 were found to be epigenetically regulated by histone post-translational modifications. Recombinant CXCL8 did not stimulate cell growth in either a normal bronchial epithelial or a squamous carcinoma cell line (SKMES-1). However, an increase was observed at 72 hours post treatment in an adenocarcinoma cell line. Conclusions: CXC (ELR+) chemokines are dysregulated in NSCLC. The balance of these chemokines may be critical in the tumour microenvironment and requires further elucidation. It remains to be seen if epigenetic targeting of these pathways is a viable therapeutic option in lung cancer treatment. © 2011 Baird et al

    Enrichment of intersubtype HIV-1 recombinants in a dual infection system using HIV-1 strain-specific siRNAs

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    <p>Abstract</p> <p>Background</p> <p>Intersubtype HIV-1 recombinants in the form of unique or stable circulating recombinants forms (CRFs) are responsible for over 20% of infections in the worldwide epidemic. Mechanisms controlling the generation, selection, and transmission of these intersubtype HIV-1 recombinants still require further investigation. All intersubtype HIV-1 recombinants are generated and evolve from initial dual infections, but are difficult to identify in the human population. In vitro studies provide the most practical system to study mechanisms, but the recombination rates are usually very low in dual infections with primary HIV-1 isolates. This study describes the use of HIV-1 isolate-specific siRNAs to enrich intersubtype HIV-1 recombinants and inhibit the parental HIV-1 isolates from a dual infection.</p> <p>Results</p> <p>Following a dual infection with subtype A and D primary HIV-1 isolates and two rounds of siRNA treatment, nearly 100% of replicative virus was resistant to a siRNA specific for an upstream target sequence in the subtype A envelope (<it>env</it>) gene as well as a siRNA specific for a downstream target sequence in the subtype D <it>env </it>gene. Only 20% (10/50) of the replicating virus had nucleotide substitutions in the siRNA-target sequence whereas the remaining 78% (39/50) harbored a recombination breakpoint that removed both siRNA target sequences, and rendered the intersubtype D/A recombinant virus resistant to the dual siRNA treatment. Since siRNAs target the newly transcribed HIV-1 mRNA, the siRNAs only enrich intersubtype env recombinants and do not influence the recombination process during reverse transcription. Using this system, a strong bias is selected for recombination breakpoints in the C2 region, whereas other HIV-1 env regions, most notably the hypervariable regions, were nearly devoid of intersubtype recombination breakpoints. Sequence conservation plays an important role in selecting for recombination breakpoints, but the lack of breakpoints in many conserved env regions suggest that other mechanisms are at play.</p> <p>Conclusion</p> <p>These findings show that siRNAs can be used as an efficient in vitro tool for enriching recombinants, to facilitate further study on mechanisms of intersubytpe HIV-1 recombination, and to generate replication-competent intersubtype recombinant proteins with a breadth in HIV-1 diversity for future vaccine studies.</p

    Prospectus, October 1, 1986

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    https://spark.parkland.edu/prospectus_1986/1023/thumbnail.jp

    No Exit? Withdrawal Rights and the Law of Corporate Reorganizations

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    Bankruptcy scholarship is largely a debate about the comparative merits of a mandatory regime on one hand and bankruptcy by free design on the other. By the standard account, the current law of corporate reorganization is mandatory. Various rules that cannot be avoided ensure that investors’ actions are limited and they do not exercise their rights against specialized assets in a way that destroys the value of a business as a whole. These rules solve collective action problems and reduce the risk of bargaining failure. But there are costs to a mandatory regime. In particular, investors cannot design their rights to achieve optimal monitoring as they could in a system of bankruptcy by free design. This Article suggests that the academic debate has missed a fundamental feature of the law. Bankruptcy operates on legal entities, not on firms in the economic sense. For this reason, sophisticated investors do not face a mandatory regime at all. The ability of investors to place assets in separate entities gives them the ability to create specific withdrawal rights in the event the firm encounters financial distress. There is nothing mandatory about rules like the automatic stay when assets can be partitioned off into legal entities that are beyond the reach of the bankruptcy judge. Thus, by partitioning assets of one economic enterprise into different legal entities, investors can create a tailored bankruptcy regime. In this way, legal entities serve as building blocks that can be combined to create specific and varied but transparent investor withdrawal rights. This regime of tailored bankruptcy has been unrecognized and underappreciated and may be preferable to both mandatory and free design regimes. By allowing a limited number of investors to opt out of bankruptcy in a particular, discrete, and visible way, investors as a group may be able to both limit the risk of bargaining failure and at the same time enjoy the disciplining effect that a withdrawal right brings with it

    The 2001 Mars In-Situ-Propellant-Production Precursor (MIP) Flight Demonstration

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    The successful performance of the five individual demonstrations of MARS IN-SITU-PROPELLANT-PRODUCTION PRECURSOR (MIP) will provide both knowledge of and confidence in the reliability of this technology. At the completion of this flight demonstration, the MIP Team will be able to: a) recommend preferred hardware configurations for the intake and adsorption of carbon dioxide from the Martian atmosphere; b) understand the performance characteristics of zirconia cells to generate propellant-grade oxygen; c) understand long-term performance characteristics of advanced solar cells/arrays operated in the actual Mars environment; d) evaluate the functionality of methods to mitigate the deposition of airborne dust onto solar arrays; and e) recommend preferred hardware designs for innovative thermal management including the radiation of heat to the outside environment

    Integration of HIV/AIDS services into African primary health care: lessons learned for health system strengthening in Mozambique - a case study

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    <p>Abstract</p> <p>Introduction</p> <p>In 2004, Mozambique, supported by large increases in international disease-specific funding, initiated a national rapid scale-up of antiretroviral treatment (ART) and HIV care through a vertical "Day Hospital" approach. Though this model showed substantial increases in people receiving treatment, it diverted scarce resources away from the primary health care (PHC) system. In 2005, the Ministry of Health (MOH) began an effort to use HIV/AIDS treatment and care resources as a means to strengthen their PHC system. The MOH worked closely with a number of NGOs to integrate HIV programs more effectively into existing public-sector PHC services.</p> <p>Case Description</p> <p>In 2005, the Ministry of Health and Health Alliance International initiated an effort in two provinces to integrate ART into the existing primary health care system through health units distributed across 23 districts. Integration included: a) placing ART services in existing units; b) retraining existing workers; c) strengthening laboratories, testing, and referral linkages; e) expanding testing in TB wards; f) integrating HIV and antenatal services; and g) improving district-level management. Discussion: By 2008, treatment was available in nearly 67 health facilities in 23 districts. Nearly 30,000 adults were on ART. Over 80,000 enrolled in the HIV/AIDS program. Loss to follow-up from antenatal and TB testing to ART services has declined from 70% to less than 10% in many integrated sites. Average time from HIV testing to ART initiation is significantly faster and adherence to ART is better in smaller peripheral clinics than in vertical day hospitals. Integration has also improved other non-HIV aspects of primary health care.</p> <p>Conclusion</p> <p>The integration approach enables the public sector PHC system to test more patients for HIV, place more patients on ART more quickly and efficiently, reduce loss-to-follow-up, and achieve greater geographic HIV care coverage compared to the vertical model. Through the integration process, HIV resources have been used to rehabilitate PHC infrastructure (including laboratories and pharmacies), strengthen supervision, fill workforce gaps, and improve patient flow between services and facilities in ways that can benefit all programs. Using aid resources to integrate and better link HIV care with existing services can strengthen wider PHC systems.</p
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