350 research outputs found

    Project ambidexterity: case of recovering schedule delay in a brownfield airport project in India

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    Planning deficiencies and consequent execution delays are likely to persist in infrastructure development projects. However, recovery of schedule delay is a less researched area. This case research, using a two-stage inquiry modeled on the grounded theory, studied the schedule delay recovery during the execution phase of a brownfield airport construction project. The analyses generated contextual evidence and ambidexterity was found to be the key underlying phenomenon for successful recovery measures. The empirical learning was validated with literature and can be used by practitioners looking to institute schedule recovery measures

    Laser Beam Profile Deformation Effect during Bragg Acousto-Optic Interaction: a Non-Paraxial Approximation

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    It is commonly known that the spatial profiles of the diffracted light beams during Bragg acousto-optic interaction are distorted due to the Bragg angle selection mechanism. All the conventional studies on this effect use the paraxial approximation. But this approximation should be amended when the incident angle of the light is large enough that the diffracted light waves do not propagate closely along the optic axis of the acousto-optic diffraction system. By using a spatial Fourier transform approach, we rigorously study the light beam profile deformation effect of the diffracted light during the Bragg acousto-optic interaction beyond the paraxial approximation. Starting from the wave equation, a set of coupled-wave equations is derived to depict the acousto-optic effect. Analytic solutions that describe the profiles of the diffracted light are derived from the acousto-optic coupled-wave equations. From the solutions, differences can be found between the ones with and without paraxial approximation

    IDENTIFYING NEW KNOWLEDGE AREAS TO STRENGTHEN THE PROJECT MANAGEMENT INSTITUTE (PMI) FRAMEWORK

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    In an increasingly volatile, uncertain, complex and ambiguous (VUCA) world, managers of capital projects are under relentless pressure to consistently meet their performance expectations. At the execution stage, managers have to constantly orchestrate competing demands on scare resources and, simultaneously, manage project operations to meet time, costs and quality compliances. This calls for simple methods to distinguish factors that could cause execution stage delays and prioritise their remedial actions. The objective, therefore, was to propose and test a methodology through empirical evidence, which could be useful for managers to focus on the distinguishing factors (rather than on all factors) to achieve execution excellence. We used a three-stage methodology leveraging the existing Project Management Institute (PMI) framework to define variables and then tested the methodology using case data generated from projects adopting a grounded theory approach. A settheoretic, multi-value qualitative comparative analysis (QCA) tool helped appropriately configure this empirical case data and a subsequent Boolean minimisation technique then identified the distinguishing factor(s) that explained superior project schedule performance. The results corroborated literature findings. Two contributions emerged from this study: (a) our methodology enabled a richer analysis of the case than what would have been possible by adopting a more conventional approach; and (b) there is a potential for a domain-specific extension of the PMI framework to cover technology transfer projects having their unique knowledge areas

    Mahanine restores RASSF1A expression by down-regulating DNMT1 and DNMT3B in prostate cancer cells

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    BACKGROUND: Hypermethylation of the promoter of the tumor suppressor gene RASSF1A silences its expression and has been found to be associated with advanced grade prostatic tumors. The DNA methyltransferase (DNMT) family of enzymes are known to be involved in the epigenetic silencing of gene expression, including RASSF1A, and are often overexpressed in prostate cancer. The present study demonstrates how mahanine, a plant-derived carbazole alkaloid, restores RASSF1A expression by down-regulating specific members of the DNMT family of proteins in prostate cancer cells. RESULTS: Using methylation-specific PCR we establish that mahanine restores the expression of RASSF1A by inducing the demethylation of its promoter in prostate cancer cells. Furthermore, we show that mahanine treatment induces the degradation of DNMT1 and DNMT3B, but not DNMT3A, via the ubiquitin-proteasome pathway; an effect which is rescued in the presence of a proteasome inhibitor, MG132. The inactivation of Akt by wortmannin, a PI3K inhibitor, results in a similar down-regulation in the levels DNMT1 and DNMT3B. Mahanine treatment results in a decline in phospho-Akt levels and a disruption in the interaction of Akt with DNMT1 and DNMT3B. Conversely, the exogenous expression of constitutively active Akt inhibits the ability of mahanine to down-regulate these DNMTs, suggesting that the degradation of DNMT1 and DNMT3B by mahanine occurs via Akt inactivation. CONCLUSIONS: Taken together, we show that mahanine treatment induces the proteasomal degradation of DNMT1 and DNMT3B via the inactivation of Akt, which facilitates the demethylation of the RASSF1A promoter and restores its expression in prostate cancer cells. Therefore, mahanine could be a potential therapeutic agent for advanced prostate cancer in men when RASSF1A expression is silenced

    Time Dynamics of Self-Pumped Reflection Gratings in a Photorefractive Polymer

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    The time dynamics of self-pumped reflection gratings in a commonly used photorefractive polymer PDCST:PVK:ECZ-BBP:C60 with no additional electron sources or traps is investigated. While holes are normally the mobile charges and responsible for grating formation, our experimental observations, analyzed using multi-exponential fitting curves, show evidence of electrons in addition to holes as charge carriers, particularly above an applied field of 40 V/μm. The dependence of effective carrier mobilities on the applied electric field, deduced from experimental results, show stronger field dependence of electron mobility at high electric fields. At an applied field of 70 V/μm, electron and hole mobilities become approximately equal, and the contribution of electrons on grating formation becomes significant

    Harvesting Single Ferroelectric Domain Stressed Nanoparticles for Optical and Ferroic Applications

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    We describe techniques to selectively harvest single ferroelectric domain nanoparticles of BaTiO3 as small as 9 nm from a plethora of nanoparticles produced by mechanical grinding. High resolution transmission electron microscopy imaging shows the unidomain atomic structure of the nanoparticles and reveals compressive and tensile surface strains which are attributed to the preservation of ferroelectric behavior in these particles. We demonstrate the positive benefits of using harvested nanoparticles in disparate liquid crystal systems

    Učinak dodatka kondenziranih tanina putem obroka od mješavine lišća Ficus infectoria i Psidium guajava na antioksidacijski status eritrocita, imunosni odgovor i želučano-crijevne obliće u janjadi (Ovis aries)

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    This experimental study was carried out to assess the effect of condensed tannins (CT) through a leaf meal mixture of Ficus infectoria and Psidium guajava, on erythrocytic antioxidant status, immune response and gastrointestinal nematodes in lambs. Twenty-four non-descript lambs were randomly divided into four groups, consisting of six lambs in each, in a completely randomized block design, and randomly allocated to 4 dietary treatments: CT-0, CT-1, CT-1.5 and CT-2 containing 0, 1, 1.5 and 2.0 percent CT, respectively. The erythrocytic antioxidant status was monitored in all lambs at 0, 45, 90, 135, 180 days of feeding, however, humoral and cell mediated immune responses were determined at the end of the feeding trial. Hemoglobin was found to be highest (P<0.05) in CT-1.5 followed by CT-1, CT-2 and CT-0, respectively. CT supplementation significantly (P<0.05) improved the antioxidant status, as indicated by increased levels of glutathione peroxidase, catalase, reduced glutathione, glutathione-S-transferase, superoxide dismutase, total thiol and protein bound thiol group and decreased lipid peroxidase in the lambs. Supplementation of CT significantly (P<0.05) improved the cell mediated immune response in lambs. The fecal egg counts (FEC) in lambs were significantly (P<0.01) higher in the control group (CT-0), followed by CT-1, CT-1.5 and CT-2. The pooled fecal cultures of the lambs revealed that the majority of the infective larvae were from Haemonchus contortus. The FEC in the control was significantly higher (P<0.05) throughout the study period compared to the CT-1.5 and CT-2 groups. It may be concluded that dietary supplementation of CT (1-2%) through LMM improved the erythrocytic antioxidant status and immune response, and reduced FEC in lambs.Istraživanje je provedeno u svrhu procjene učinka kondenziranih tanina (KT), dodanih putem obroka od mješavine lišća Ficus infectoria i Psidium guajava, na antioksidacijski status eritrocita, imunosni odgovor i želučano-crijevne obliće u janjadi. Dvadeset i četiri janjeta slučajnim su odabirom bila razvrstana u četiri skupine po šest janjadi u svakoj skupini. Randomiziranim kompletnim blok-dizajnom i nasumičnim pridjeljivanjem formirane su četiri skupine s različitim udjelom KT u obroku: skupina KT-0 (0% KT), skupina KT-1 (1%), skupina KT-1,5 (1,5%) i skupina KT-2 (2%). Kod sve janjadi praćen je antioksidacijski status eritrocita 0., 45., 90., 135. i 180. dan hranidbe, a na kraju istraživanja određen je humoralni i stanični imunosni odgovor. Najviša razina (P<0,05) haemoglobina utvrđena je u skupini KT-1,5 nakon koje su slijedile skupine KT-1, KT-2 i KT-0. Dodani je KT signifikantno (P<0,05) poboljšao antioksidacijski status janjadi što su pokazale povišene razine glutation-peroksidaze, katalaze, zatim redukcija razine glutationa, glutation-S-transferaze, superoksid-dismutaze, ukupnog tiola i protein vezane tiol skupine kao i sniženje razine lipidne peroksidaze. Dodavanje KT signifikantno je (P<0,05) poboljšalo stanični imunosni odgovor janjadi. Broj jaja u fecesu bio je signifikantno (P<0,01) viši u kontrolnoj skupini (KT-0) janjadi nakon koje su slijedile skupine KT-1, KT-1,5 i KT-2. Skupne kulture iz fecesa janjadi pokazale su da većina invazivnih larvi pripada vrsti Haemonchus contortus. Broj jaja u fecesu kontrolne skupine janjadi bio je tijekom cijeloga istraživanog razdoblja signifikantno povišen (P<0,05) u odnosu na skupine KT-1,5 i KT-2. Može se zaključiti da je dodavanjem mješavine lišća s 1 – 2% KT u obroku kod janjadi poboljšan antioksidacijski status eritrocita i imunosni odgovor te smanjen broj prazitskih jajašaca u fecesu

    Cryptic Eimeria genotypes are common across the southern but not northern hemisphere

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    The phylum Apicomplexa includes parasites of medical, zoonotic and veterinary significance. Understanding the global distribution and genetic diversity of these protozoa is of fundamental importance for efficient, robust and long-lasting methods of control. Eimeria spp. cause intestinal coccidiosis in all major livestock animals and are the most important parasites of domestic chickens in terms of both economic impact and animal welfare. Despite having significant negative impacts on the efficiency of food production, many fundamental questions relating to the global distribution and genetic variation of Eimeria spp. remain largely unanswered. Here, we provide the broadest map yet of Eimeria occurrence for domestic chickens, confirming that all the known species (Eimeria acervulina, Eimeria brunetti, Eimeria maxima, Eimeria mitis, Eimeria necatrix, Eimeria praecox, Eimeria tenella) are present in all six continents where chickens are found (including 21 countries). Analysis of 248 internal transcribed spacer sequences derived from 17 countries provided evidence of possible allopatric diversity for species such as E. tenella (FST values ⩽0.34) but not E. acervulina and E. mitis, and highlighted a trend towards widespread genetic variance. We found that three genetic variants described previously only in Australia and southern Africa (operational taxonomic units x, y and z) have a wide distribution across the southern, but not the northern hemisphere. While the drivers for such a polarised distribution of these operational taxonomic unit genotypes remains unclear, the occurrence of genetically variant Eimeria may pose a risk to food security and animal welfare in Europe and North America should these parasites spread to the northern hemisphere

    The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia Type 3 pathogenesis

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    DNA strand-breaks (SBs) with non-ligatable ends are generated by ionizing radiation, oxidative stress, various chemotherapeutic agents, and also as base excision repair (BER) intermediates. Several neurological diseases have already been identified as being due to a deficiency in DNA end-processing activities. Two common dirty ends, 3'-P and 5'-OH, are processed by mammalian polynucleotide kinase 3'-phosphatase (PNKP), a bifunctional enzyme with 3'-phosphatase and 5'-kinase activities. We have made the unexpected observation that PNKP stably associates with Ataxin-3 (ATXN3), a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD). This disease is one of the most common dominantly inherited ataxias worldwide; the defect in SCA3 is due to CAG repeat expansion (from the normal 14-41 to 55-82 repeats) in the ATXN3 coding region. However, how the expanded form gains its toxic function is still not clearly understood. Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity. Furthermore, transgenic mice conditionally expressing the pathological form of human ATXN3 also showed decreased 3'-phosphatase activity of PNKP, mostly in the deep cerebellar nuclei, one of the most affected regions in MJD patients' brain. Finally, long amplicon quantitative PCR analysis of human MJD patients' brain samples showed a significant accumulation of DNA strand breaks. Our results thus indicate that the accumulation of DNA strand breaks due to functional deficiency of PNKP is etiologically linked to the pathogenesis of SCA3/MJD.This research was supported by USPHS grant NS073976 (TKH) and P30 ES 06676 that support the NIEHS Center Cell Biology Core and Molecular Genomics Core of UTMB’s NIEHS Center for DNA sequencing. TKP is supported by CA129537 and CA154320. This work was also supported by Fundação para a Ciência e Tecnologia through the project [PTDC/SAU-GMG/101572/2008] and through fellowships [SFRH/BPD/91562/2012 to ASF, SFRH/BD/51059/2010 to ANC]. IB is supported by NIEHS R01 ES018948 and NIAID/AI06288
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