994 resultados para dramatic monologue


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This master thesis studies how trade liberalization affects the firm-level productivity and industrial evolution. To do so, I built a dynamic model that considers firm-level productivity as endogenous to investigate the influence of trade on firm’s productivity and the market structure. In the framework, heterogeneous firms in the same industry operate differently in equilibrium. Specifically, firms are ex ante identical but heterogeneity arises as an equilibrium outcome. Under the setting of monopolistic competition, this type of model yields an industry that is represented not by a steady-state outcome, but by an evolution that rely on the decisions made by individual firms. I prove that trade liberalization has a general positive impact on technological adoption rates and hence increases the firm-level productivity. Besides, this endogenous technology adoption model also captures the stylized facts: exporting firms are larger and more productive than their non-exporting counterparts in the same sector. I assume that the number of firms is endogenous, since, according to the empirical literature, the industrial evolution shows considerably different patterns across countries; some industries experience large scale of firms’ exit in the period of contracting market shares, while some industries display relative stable number of firms or gradually increase quantities. The special word “shakeout” is used to describe the dramatic decrease in the number of firms. In order to explain the causes of shakeout, I construct a model where forward-looking firms decide to enter and exit the market on the basis of their state of technology. In equilibrium, firms choose different dates to adopt innovation which generate a gradual diffusion process. It is exactly this gradual diffusion process that generates the rapid, large-scale exit phenomenon. Specifically, it demonstrates that there is a positive feedback between firm’s exit and adoption, the reduction in the number of firms increases the incentives for remaining firms to adopt innovation. Therefore, in the setting of complete information, this model not only generates a shakeout but also captures the stability of an industry. However, the solely national view of industrial evolution neglects the importance of international trade in determining the shape of market structure. In particular, I show that the higher trade barriers lead to more fragile markets, encouraging the over-entry in the initial stage of industry life cycle and raising the probability of a shakeout. Therefore, more liberalized trade generates more stable market structure from both national and international viewpoints. The main references are Ederington and McCalman(2008,2009).

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Nb3Sn growth following the bronze technique, (i.e. by interdiffusion between Cu(Sn) alloy (bronze) and Nb) is one of the important methodologies to produce this superconductor. In this study, we have addressed the confusion over the growth rate of the Nb3Sn phase. Furthermore, a possible explanation for the corrugated layer in the multifilamentary structure is discussed. Kirkendall marker experiments were conducted to study the relative mobilities of the species, which also explained the reason for finding pores in the product phase layer. Based on the parabolic growth constant at different temperatures, the activation energy for the growth is determined. We have further explained the dramatic increase in the growth rate of the prod

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Many Finnish IT companies have gone through numerous organizational changes over the past decades. This book draws attention to how stability may be central to software product development experts and IT workers more generally, who continuously have to cope with such change in their workplaces. It does so by analyzing and theorizing change and stability as intertwined and co-existent, thus throwing light on how it is possible that, for example, even if ‘the walls fall down the blokes just code’ and maintain a sense of stability in their daily work. Rather than reproducing the picture of software product development as exciting cutting edge activities and organizational change as dramatic episodes, the study takes the reader beyond the myths surrounding these phenomena to the mundane practices, routines and organizings in product development during organizational change. An analysis of these ordinary practices offers insights into how software product development experts actively engage in constructing stability during organizational change through a variety of practices, including solidarity, homosociality, close relations to products, instrumental or functional views on products, preoccupations with certain tasks and humble obedience. Consequently, the study shows that it may be more appropriate to talk about varieties of stability, characterized by a multitude of practices of stabilizing rather than states of stagnation. Looking at different practices of stability in depth shows the creation of software as an arena for micro-politics, power relations and increasing pressures for order and formalization. The thesis gives particular attention to power relations and processes of positioning following organizational change: how social actors come to understand themselves in the context of ongoing organizational change, how they comply with and/or contest dominant meanings, how they identify and dis-identify with formalization, and how power relations often are reproduced despite dis-identification. Related to processes of positioning, the reader is also given a glimpse into what being at work in a male-dominated and relatively homogeneous work environment looks like. It shows how the strong presence of men or “blokes” of a particular age and education seems to become invisible in workplace talk that appears ‘non-conscious’ of gender.

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Cancer is becoming the leading cause of deaths in the world. As 90% of all deaths from cancer are caused by metastasis, discovery of the mechanisms behind cancer cell invasion and metastasis is of utmost importance. Only new effective therapies targeting cancer progression can reduce cancer mortality rates. The aim of this study was to identify molecules that are relevant for tumor cell invasion and spreading in fibrosarcomas and melanomas, and to analyze their potential for cancer biomarkers or therapeutic targets. First, the gene expression changes of normal cells and transformed cells showing high invasiveness, S-adenosylmethionine decarboxylase (AdoMetDC)-transfected murine fibroblasts and human melanoma cells, were studied by microarray analyses. The function of the identified candidate molecules were then studied in detail in these cell lines. Finally, the physiological relevance of the identified changes was studied by immunohistochemical analyses of human sarcoma and melanoma specimens or by a mouse xenograft model. In fibrosarcoma cells, the most remarkable change detected was a dramatic up-regulation of the actin-sequestering molecule thymosin beta 4 (TB4), which was shown to be important for the transformed phenotype of the AdoMetDC-transfected cells (Amdc-s and -as). A sponge toxin latrunculin A, inhibiting the binding of TB4 to actin, was found to selectively inhibit the migration and invasion of these cells. Further, Amdc-s-induced mouse tumors and human high-grade sarcomas were found to show intense TB4 immunostaining. In addition to TB4, integrin subunits alfa 6 and beta 7 (ItgA6 and ItgB7) were found to be up-regulated in Amdc-s and -as cells. ItgA6 was shown to dimerize mainly with ItgB1 in Amdc-s. Inhibition of ItgA6 or ItgB1 function with neutralizing antibodies fully blocked the invasiveness of Amdc-s cells, and importantly also human HT-1080 fibrosarcoma cells, in three-dimensional (3D)-Matrigel mimicking tumor extracellular matrix (ECM). By immunohistochemical analyses, strong staining for ITGA6 was detected in human high-grade fibrosarcomas and other sarcomas, especially at the invasion fronts of the tumors. In the studied melanoma cell lines, the expression levels of the adhesion-related ECM proteins tenascin-C (TN-C), fibronectin (FN), and transforming growth factor beta-induced (TGFBI) were found to be highly up-regulated. By immunohistochemistry, intense TN-C and FN staining was detected in invasive and metastatic melanoma tumors, showing co-localization (together with procollagen-I) in tubular meshworks and channels around the invading melanoma cells. In vitro, TN-C and FN were further found to directly stimulate the migration of melanoma cells in 3D-collagen-I matrix. The third candidate protein, TGFBI, was found to be an anti-adhesive molecule for melanoma cells, and knockdown of its expression in metastatic melanoma cells (TGFBI-KD cells) led to dramatically impaired tumor growth in immunocompromized mice. Interestingly, the control tumors showed intense TGFBI immunostaining in the invasion fronts, showing partial co-localization with the fibrillar FN staining, whereas the small TGFBI-KD cell-induced tumors displayed amorphous, non-fibrillar FN staining. These data suggest an important role for TGFBI in FN fibrillogenesis and melanoma progression. In conclusion, we have identified several invasion-related molecules, which show potential for cancer diagnostic or prognostic markers, or therapeutic targets. Based on our previous and present fibrosarcoma studies, we propose the possibility of using ITGA6 antagonists (affecting tumor cell adhesion) in combination with TB4 inhibitors (affecting tumor cell migration) and cathepsin L inhibitors (affecting the degradation of basement membrane and ECM proteins) for the treatment of fibrosarcomas and other tumors overexpressing these molecules. With melanoma cells, in turn, we point to the importance of three secreted ECM proteins, TN-C, FN, and TGFBI, in melanoma progression. Of these, especially the potential of TN-C as a prognostic melanoma biomarker and TGFBI as a promising therapeutic target molecule are clearly worth additional studies.

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Soilla on merkittävä rooli ilmastonmuutoksen hillitsemisessä suuren hiilivarastonsa sekä ekosysteemin ja ilmakehän välisen kaasunvaihdon ansiosta. Ilmastonmuutoksen ennustetaan vaikuttavan suokasvillisuuteen ja suon toimintaan epäsuorasti. Vedenpinnan ennustetaan laskevan 14–21 cm johtuen kasveista ja avoimilta pinnoilta tapahtuvan haihdunnan lisääntymisestä lämpötilan noustessa, mikäli sadanta ei lisäänny. Aiemmat vedenpinnan laskun jälkeistä kasvillisuutta seuranneet tutkimukset ovat osoittaneet, että putkilokasvit hyötyvät alhaisemmasta vedenpinnan tasosta ja että kuljuun sopeutuneet rahkasammalet kärsivät kuivuneista oloista. Kasvillisuuden runsaussuhteiden muuttumisen lisäksi kasviyhteisöjen monimuotoisuus vähenee. Erityisen herkkiä vedenpinnan laskulle ovat olleet välipinta- ja kuljurahkasammalet ja sarat. Funktionaalisten kasviryhmien vasteiden selvittämiksesi käytettiin BACI (before-after-control-impact) –tutkimusotetta. Tutkimuksessa oli kolme verrokkialaa ja kolme käsittelyalaa, joissa vedenpintaa oli laskettu 14–21 senttimetriin. Lisäksi vertailukohdaksi tutkimuksessa oli mukana kolme alaa, joissa oli tehty metsäojitus n. 50 vuotta sitten. Nämä toistot sijaitsivat meso-, oligo ombrotrofisilla suotyypeillä Oriveden Lakkasuolla. Kasvillisuus kartoitettiin ja vedenpinnat mitattiin aloilta ennen käsittelyä vuonna 2000 sekä vuosina 2001–2003 ja 2009. Aineisto analysoitiin TWINSPAN- (PC-Ord), PRC ja DCA (CANOCO)-monimuuttujamenetelmillä. Tulokset osoittivat, että verrokki- ja käsittelyalat olivat samanlaisia lähtökohdiltaan, joten niitä voitiin käsittelyn jälkeen verrata toisiinsa. Kasvillisuuden rakenne vaihteli vuosien välillä myös verrokkialoilla, mikä osoittaa kasvien sopeutumiskyvyn muuttuviin sääoloihin (lämpötila, sademäärä). Vuosi 2003 erottui tutkimuksessa alhaisella vedenpinnantasolla, mutta toisaalta myös ainavihantien varpujen suuren peittävyyden osalta. Vuoteen 2009 mennessä kasvillisuuden erityisesti sarojen peittävyys väheni. Ravinteikkaimmilla toistoilla kasvillisuuden vasteet vaikuttivat olevan vahvemmat kuin vähäravinteisilla toistoilla. Kasviryhmistä kulju- ja välipintasammalilla oli vahvimmat vasteetvedenpinnan laskuun ja mätäslajeilla heikoimmat. Tulosten mukaan kasviryhmien vasteet vaihtelevat riippuen tarkasteltavasta aikajaksosta: ensimmäiset kolme vuotta käsittelyn jälkeen suo oli häiriötilassa ja vasta sen jälkeen kasvillisuus sopeutui muuttuneisiin oloihin.

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AIMS An independent, powerful coronary heart disease (CHD) predictor is a low level of high-density lipoprotein cholesterol (HDL-C). Discoidal preβ-HDL particles and large HDL2 particles are the primary cholesterol acceptors in reverse cholesterol transport, a key anti-atherogenic HDL mechanism. The quality of HDL subspecies may provide better markers of HDL functionality than does HDL-C alone. We aimed I) to study whether alterations in the HDL subspecies profile exist in low-HDL-C subjects II) to explore the relationship of any changes in HDL subspecies profile in relation to atherosclerosis and metabolic syndrome; III) to elucidate the impact of genetics and acquired obesity on HDL subspecies distribution. SUBJECTS The study consisted of 3 cohorts: A) Finnish families with low HDL-C and premature CHD (Study I: 67 subjects with familial low HDL-C and 64 controls; Study II: 83 subjects with familial low HDL-C, 65 family members with normal HDL-C, and 133 controls); B) a cohort of 113 low- and 133 high-HDL-C subjects from the Health 2000 Health Examination Survey carried out in Finland (Study III); and C) a Finnish cohort of healthy young adult twins (52 monozygotic and 89 dizygotic pairs) (Study IV). RESULTS AND CONCLUSIONS The subjects with familial low HDL-C had a lower preβ-HDL concentration than did controls, and the low-HDL-C subjects displayed a dramatic reduction (50-70%) in the proportion of large HDL2b particles. The subjects with familial low HDL-C had increased carotid atherosclerosis measured as intima-media-thickness (IMT), and HDL2b particles correlated negatively with IMT. The reduction in both key cholesterol acceptors, preβ-HDL and HDL2 particles, supports the concept of impaired reverse cholesterol transport contributing to the higher CHD risk in low-HDL-C subjects. The family members with normal HDL-C and the young adult twins with acquired obesity showed a reduction in large HDL2 particles and an increase in small HDL3 particles, which may be the first changes leading to the lowering of HDL-C. The low-HDL-C subjects had a higher serum apolipoprotein E (apoE) concentration, which correlated positively with the metabolic syndrome components (waist circumference, TG, and glucose), highlighting the need for a better understanding of apoE metabolism in human atherosclerosis. In the twin study, the increase in small HDL3b particles was associated with obesity independent of genetic effects. The heritability estimate, of 73% for HDL-C and 46 to 63% for HDL subspecies, however, demonstrated a strong genetic influence. These results suggest that the relationship between obesity and lipoproteins depends on different elements in each subject. Finally, instead of merely elevating HDL-C, large HDL2 particles and discoidal preβ-HDL particles may provide beneficial targets for HDL-targeted therapy.

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Guanine rich sequences adopt a variety of four stranded structures, which differ in strand orientation and conformation about the glycosidic bond even though they are all stabilised by Hoogsteen hydrogen bonded guanine tetrads. Detailed model building and molecular mechanics calculations have been carried out to investigate various possible conformations of guanines along a strand and different possible orientations of guanine strands in a G-tetraplex structure. It is found that for an oligo G stretch per se, a parallel four stranded structure with all guanines in anti conformation is favoured over other possible tetraplex structures. Hence an alternating syn-anti arrangement of guanines along a strand is likely to occur only in folded back tetraplex structures with antiparallel G strands. Our study provides a theoretical rationale for the observed alternation of glycosidic conformation and the inverted stacking arrangement arising from base flipover, in antiparallel G-tetraplex structures and also highlights the various structural features arising due to different types of strand orientations. The molecular mechanics calculations help in elucidating the various interactions which stabilize different G-tetraplex structures and indicate that screening of phosphate charge by counterions could have a dramatic effect on groove width in these four stranded structures.

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Guanlne rich sequences adopt a variety of four stranded structures, which differ in strand orientation and conformation about the glycosldic bond even though they are all stabilised by Hoogsteen hydrogen bonded guanlne tetrads. Detailed model building and molecular mechanics calculations have been carried out to investigate various possible conformations of guanlnes along a strand and different possible orientations of guanlne strands In a G-tetraplex structure. It is found that for an ollgo G stretch per se, a parallel four stranded structure with all guanines In anti conformation is favoured over other possible tetraplex structures. Hence an alternating syn-anti arrangement of guanlnes along a strand is likely to occur only in folded back tetraplex structures with antiparallel G strands. Our study provides a theoretical rationale for the observed alternation of glycosldic conformation and the inverted stacking arrangement arising from base filpover, In antlparallel G-tetraplex structures and also highlights the various structural features arising due to different types of strand orientations. The molecular mechanics calculations help in elucidating the various interactions which stabilize different G-tetraplex structures and indicate that screening of phosphate charge by counterions could have a dramatic effect on groove width in these four stranded structures.

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he ultrastructure of purified rinderpest virus and intracellular viral nucleocapsids from infected vero cells treated with a subtoxic dose of 5-fluorouracil (5-Fu) (1 mug/ml), has been analysed by transmission electron microscopy, and compared with that of normal virus particle and nucleocapsids. The results reveal dramatic alterations in the structure of both virions and nucleocapsids. The surface glycoprotein projection of virions was not seen or present at a much reduced level. The intracellular nucleocapsids showed pronounced structural changes,with respect to size, shape and fine structure. The length of treated nucleocapsids is much smaller as compared to the control. The central hollow core is missing in case of drug-treated nucleocapsid and the herring bone structure is replaced by a 'beads on string' structure. The presence of N protein, which is a major structural component of nucleocapsids was seen in 5-Fu-treated cells, but it was associated with a predominantly diffused form of nucleocapsids as seen by immunoelectron microscopy. We report here the first definitive and visual evidence of altered structure of virions and their nucleocapsids after 5-Fu treatment

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Purine nucleotide synthesis in Plasmodium falciparum takes place solely by the purine salvage pathway in which preformed purine base(s) are salvaged from the host and acted upon by a battery of enzymes to generate AMP and GMP. Inhibitors of this pathway have a potent effect on the in vitro growth of P. falciparum and are hence, implicated as promising leads for the development of new generation anti-malarials. Here, we describe the mechanism of inhibition of the intraerythrocytic growth of P. falciparum by the purine nucleoside precursor, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). Our results show that AICAR toxicity is mediated through the erythrocyte in which AICAR is phosphorylated to its nucleotide, ZMP. Further, purine metabolite labeling of the parasitized erythrocytes by H-3]-hypoxanthine, in the presence of AICAR, showed a significant decrease in radioactive counts in adenylate fractions but not in guanylate fractions. The most dramatic effect on parasite growth was observed when erythrocytes pretreated with AICAR were used in culture. Pretreatment of erythrocytes with AICAR led to significant intracellular accumulation of ZMP and these erythrocytes were incapable of supporting parasite growth. These results implicate that in addition to the purine salvage pathway in P. falciparum, AICAR alters the metabolic status of the erythrocytes, which inhibits parasite growth. As AICAR and ZMP are metabolites in the human serum and erythrocytes, our studies reported here throw light on their possible role in disease susceptibility, and also suggests the possibility of AICAR being a potential prophylactic or chemotherapeutic anti-malarial compound. (C) 2011 Elsevier B.V. All rights reserved.

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Electron transfer reactions in large molecules may often be coupled to both the polar solvent modes and the intramolecular vibrational modes of the molecule. This can give rise to a complex dynamics which may in some systems, like betaine, be controlled more by vibrational rather than by solvent effects. Additionally, a significant contribution from an ultrafast relaxation component in the solvation dynamics may enhance the complexity. To explain the wide range of behavior that has been observed experimentally, Barbara et al. recently proposed that a model of an electron transfer reaction should minimally consist of a low-frequency classical solvent mode (X), a low-frequency vibrational mode (Q), and a high-frequency quantum mode (q) (J. Phys. Chem. 1991, 96, 3728). In the present work, a theoretical study of this model is described. This study generalizes earlier work by including the biphasic solvent response and the dynamics of the low-frequency vibrational mode in the presence of a delocalized, extended reaction zone. A novel Green's function technique has been developed which allowed us to study the non-Markovian dynamics on a multidimensional surface. The contributions from the high-frequency vibrational mode and the ultrafast component in the non-Markovian solvent dynamics are found to be primarily responsible for the dramatic increase in charge transfer rate over the prediction of the classical theories that neglect both these factors. These, along with a large coupling between the reactant and the product states, may combine to render the electron transfer rate both very large and constant over a wide range of solvent relaxation rates. A study on the free energy gap dependence of the electron transfer rate reveals that the rates are sensitive to changes in the quantum frequency particularly when the free energy gap is very large.

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Measurement of dipolar couplings using separated local field (SLF) NMR experiment is a powerful tool for structural and dynamics studies of oriented molecules such as liquid crystals and membrane proteins in aligned lipid bilayers. Enhancing the sensitivity of such SLF techniques is of significant importance in present-day solid-state NMR methodology. The present study considers the use of adiabatic cross-polarization for this purpose, which is applied for the first time to one of the well-known SLF techniques, namely, polarization inversion spin exchange at the magic angle (PISEMA). The experiments have been carried out on a single crystal of a model peptide, and a dramatic enhancement in signal-to-noise up to 90% has been demonstrated.

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Cys126 is a completely conserved residue in triosephosphate isomerase that is proximal to the active site but has been ascribed no specific role in catalysis. A previous study of the C126S and C126A mutants of yeast TIM reported substantial catalytic activity for the mutant enzymes, leading to the suggestion that this residue is implicated in folding and stability [Gonzalez-Mondragon E et al. (2004) Biochemistry43, 3255–3263]. We re-examined the role of Cys126 with the Plasmodium falciparum enzyme as a model. Five mutants, C126S, C126A, C126V, C126M, and C126T, were characterized. Crystal structures of the 3-phosphoglycolate-bound C126S mutant and the unliganded forms of the C126S and C126A mutants were determined at a resolution of 1.7–2.1 Å. Kinetic studies revealed an approximately five-fold drop in kcat for the C126S and C126A mutants, whereas an approximately 10-fold drop was observed for the other three mutants. At ambient temperature, the wild-type enzyme and all five mutants showed no concentration dependence of activity. At higher temperatures (> 40 °C), the mutants showed a significant concentration dependence, with a dramatic loss in activity below 15 μm. The mutants also had diminished thermal stability at low concentration, as monitored by far-UV CD. These results suggest that Cys126 contributes to the stability of the dimer interface through a network of interactions involving His95, Glu97, and Arg98, which form direct contacts across the dimer interface.

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We report a dramatic change in effective three-photon absorption coefficient of amorphous Ge16As29Se55 thin films, when its optical band gap decreases by 10 meV with 532 nm light illumination. This large change provides valuable information on the higher excited states, which are otherwise inaccessible via normal optical absorption. The results also indicate that photodarkening in chalcogenide glasses can serve as an effective tool to tune the multiphoton absorption in a rather simple way. (C) 2011 American Institute of Physics.

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We have synthesized five new cholesterol based gemini cationic lipids possessing hydroxyethyl (-CH2CH2OH) function on each head group, which differ in the length of the polymethylene spacer chain. These gemini lipids are important for gene delivery processes as they possess pre-optimized molecular features, e. g., cholesterol backbone, ether linkage and a variable spacer chain between both the headgroups of the gemini lipids. Cationic liposomes were prepared from each of these lipids individually and as a mixture of individual cationic gemini lipid and 1,2-dioleoyl phosphatidylethanolamine (DOPE). Each gemini lipid based formulation induced better transfection activity than that of their monomeric counterpart. One such gemini lipid with a -(CH2)(12)-spacer, HG-12, showed dramatic increase in the mean fluorescence intensity due to the expression of green-fluorescence protein (GFP) in the presence of 10% FBS compared to the conditions where there was no serum. Other gemini lipids retained their gene transfection efficiency without any marked decrease in the presence of serum. The only exception was seen with the gemini with a -(CH2)(3)-spacer, HG-3, which on gene transfection in the presence of 10% FBS lost similar to 70% of its transfection efficiency. Overall the gemini lipid with a -(CH2)(5)-spacer, HG-5, showed the highest transfection activity at N/P (lipid/DNA) ratio of 0.5 and lipid : DOPE molar ratio of 2. Upon comparison of the relevant parameters, e. g., %-transfected cells, the amount of DNA transfected to each cell and %-cell viability all together against Lipofectamine 2000, one of the best commercial transfecting agents, the optimized lipid formulation based on DOPE/HG-5 was found to be comparable. In terms of its ability to induce gene-transfer in the presence of serum and shelf-life DOPE/HG-5 liposome was found to be superior to its commercial counterpart. Confocal imaging analysis confirmed that in the presence of 10% serum using a Lipid : DOPE of 1 : 4 and N/P charge ratio of 0.75 with 1.2 mu g DNA per well, HG-5 is better than Lipofectamine 2000.