Manipulation of the surface pegylation in combination with reduced vesicle size of cationic liposomal adjuvants modifies their clearance kinetics from the injection site, and the rate and type of T cell response

The mechanism behind the immunostimulatory effect of the cationic liposomal vaccine adjuvant dimethyldioctadecylammonium and trehalose 6,6′- dibehenate (DDA:TDB) has been linked to the ability of these cationic vesicles to promote a depot after administration, with the liposomal adjuvant and the antigen both being retained at the injection site. This can be attributed to their cationic nature, since reduction in vesicle size does not influence their distribution profile yet neutral or anionic liposomes have more rapid clearance rates. Therefore the aim of this study was to investigate the impact of a combination of reduced vesicle size and surface pegylation on the biodistribution and adjuvanticity of the formulations, in a bid to further manipulate the pharmacokinetic profiles of these adjuvants. From the biodistribution studies, it was found that with small unilamellar vesicles (SUVs), 10% PEGylation of the formulation could influence liposome retention at the injection site after 4 days, whilst higher levels (25 mol%) of PEG blocked the formation of a depot and promote clearance to the draining lymph nodes. Interestingly, whilst the use of 10% PEG in the small unilamellar vesicles did not block the formation of a depot at the site of injection, it did result in earlier antibody response rates and switch the type of T cell responses from a Th1 to a Th2 bias suggesting that the presence of PEG in the formulation not only control the biodistribution of the vaccine, but also results in different types of interactions with innate immune cells. © 2012 Elsevier B.V.

Nanopatterned UV curable hydrogels for biomedical applications

With an increasing use of emerging patterning technologies such as UV-NIL in biotechnological applications there is at the same time a raising demand for new material for such applications. Here we present a PEG based precursor mixed with a photoinitiator to make it UV sensitive as a new material aimed at biotechnological applications. Using HSQ patterned quartz stamps we observed excellent pattern replication indicating good flow properties of the resist. We were able to obtain imprints with <20 nm residual layer. The PEG based resist has hydrogel properties and it swelling in water was observed by AFM.

Cerebellar morphology in developmental dyslexia

Recent evidence has suggested cerebellar anomalies in developmental dyslexia. Therefore, we investigated cerebellar morphology in subjects with documented reading disabilities. We obtained T1-weighted magnetic resonance images in the coronal and sagittal planes from 11 males with prior histories of developmental dyslexia, and nine similarly-aged male controls. Proton magnetic resonance spectra (TE=136 ms, TR=2.4 s) were obtained bilaterally in the cerebellum. Phonological decoding skill was measured using non-word reading. Handedness was assessed using both the Annett questionnaire of hand preference and Annett’s peg moving task. Cerebellar symmetry was observed in the dyslexics but there was significant asymmetry (right grey matter>left grey matter) in controls. The interpretation of these results depended whether a motor- or questionnaire-based method was used to determine handedness. The degree of cerebellar symmetry was correlated with the severity of dyslexics’ phonological decoding deficit. Those with more symmetric cerebella made more errors on a nonsense word reading measure of phonological decoding ability. Left cerebellar metabolite ratios were shown to correlate significantly with the degree of cerebellar asymmetry (P<0.05) in controls. This relationship was absent in developmental dyslexics. Cerebellar morphology reflects the higher degree of symmetry found previously in the temporal and parietal cortex of dyslexics. The relationship of cerebellar asymmetry to phonological decoding ability and handedness, together with our previous finding of altered metabolite ratios in the cerebellum of dyslexics, lead us to suggest that there are alterations in the neurological organisation of the cerebellum which relate to phonological decoding skills, in addition to motor skills and handedness.

Bioactive organic/inorganic hybrids with improved mechanical performance

New sol-gel functionalized poly-ethylene glycol (PEGM)/SiO2-CaO hybrids were prepared with interpenetrating networks of silica and PEGM through the formation of Si-O-Si bonds. Bioactive and mechanical properties were investigated for a series of hybrids containing varying organic/inorganic ratios and PEG molecular weights. In contrast to the unmodified PEG/SiO2-CaO hybrids, which rapidly dissolved and crumbled, the epoxy modified hybrids exhibited good mechanical properties and bioactivity. The compressive strength and Young's modulus were greater for higher molecular weight PEGM hybrids (PEGM600 compared to PEGM300). Compressive strengths of 138 MPa and 81 MPa were found for the 50: 50 and 60: 40 organic/inorganic hybrid samples respectively, which are comparable with cortical bone. Young's modulus values of ∼800 MPa were obtained for the 50 : 50 and 60 : 40 organic/inorganic hybrids. Bioactivity tests were conducted by immersing the hybrids into simulated body fluid and observing the formation of apatite. Apatite formation was observed within 24 hours of immersion. PEGM600 hybrids showed enhanced apatite formation compared to PEGM300 hybrids. Increased apatite formation was observed with increasing organic/inorganic ratio. 70 : 30 and 60 : 40 hybrids exhibited the greatest apatite formation. All PEGM hybrids samples had good cell viability and proliferation. The 60 : 40 PEGM600 hybrids displayed the optimal combination of bioactivity and mechanical strength. The bioactivity of these hybrids, combined with the enhanced mechanical properties, demonstrate that these materials have significant potential for bone regeneration applications.

An in-vitro-in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management

The natural selection of anticoagulant resistant rats has resulted in a need for an alternative to anticoagulant rodenticides which differs in both active ingredient and in the method of dosing. Cholecalciferol toxicity to rodents using the dermal route is demonstrated using a variety of penetration enhancing formulations in two in-vitro models and finally in-vivo. A 1 ml dose of 50/50 (v/v) DMSO/ethanol containing 15% (v/v) PEG 200 and 20% (w/v) cholecalciferol was judged as 'sufficiently effective' in line with the European Union's Biocidal Products Regulation (No. 528/2012) during in-vivo studies. This dose was found to cause 100% mortality in a rat population in 64.4 h (±22 h).

Functional carbon nanotubes for photonic applications

Carbon nanomaterials are an active frontier of research in current nanotechnology. Single wall Carbon Nanotube (SWNT) is a unique material which has already found several applications in photonics, electronics, sensors and drug delivery. This thesis presents a summary of the author’s research on functionalisation of SWNTs, a study of their optical properties, and potential for an application in laser physics. The first significant result is a breakthrough in controlling the size of SWNT bundles by varying the salt concentrations in N-methyl 2-pyrrolidone (NMP) through a salting out effect. The addition of Sodium iodide leads to self-assembly of CNTs into recognizable bundles. Furthermore, a stable dispersion can be made via addition polyvinylpyrrolidone (PVP) polymer to SWNTs-NMP dispersion, which indicates a promising direction for SWNT bundle engineering in organic solvents. The second set of experiments are concerned with enhancement of photoluminescence (PL), through the formation of novel macromolecular complexes of SWNTs with polymethine dyes with emission from enhanced nanotubes in the range of dye excitation. The effect appears to originate from exciton energy transfer within the solution. Thirdly, SWNT base-saturable absorbers (SA) were developed and applied to mode locking of fibre lasers. SWNT-based SAs were applied in both composite and liquid dispersion forms and achieved stable ultrashort generation at 1000nm, 1550nm, and 1800 nm for Ytterbium, Erbium and Thulium-doped fibre laser respectively. The work presented here demonstrates several innovative approaches for development of rapid functionalised SWNT-based dispersions and composites with potential for application in various photonic devices at low cost.

Isolator-free switchable uni- and bidirectional hybrid mode-locked erbium-doped fiber laser

An Erbium-doped fibre ring laser hybrid mode-locked with single-wall carbon nanotubes (SWNT) and nonlinear polarisation evolution (NPE) without an optical isolator has been investigated for various cavity conditions. Precise control of the state of polarisation (SOP) in the cavity ensures different losses for counter-propagating optical fields. As the result, the laser operates in quasi-unidirectional regime in both clockwise (CW) and counter-clockwise (CCW) directions with the emission strengths difference of the directions of 22 dB. Furthermore, by adjusting the net birefringence in the cavity, the laser can operate in a bidirectional generation. In this case, a laser pumped with 75 mW power at 980 nm generates almost identical 790 and 570 fs soliton pulses with an average power of 1.17 and 1.11 mW. The operation stability and pulse quality of the soliton pulses in both unidirectional regimes are highly competitive with those generated in conventional ring fibre lasers with isolator in the cavity. Demonstrated bidirectional laser operation can find vital applications in gyroscopes or precision rotation sensing technologies.

The threat of "currency wars": A European perspective

The ‘currency war’, as it has become known, has three aspects: 1) the inflexible pegs of undervalued currencies; 2) recent attempts by floating exchange-rate countries to resist currency appreciation; 3) quantitative easing. Europe should primarily be concerned about the first issue, which relates to the renewed debate about the international monetary system. The attempts of floating exchange-rate countries to resist currency appreciation are generally justified while China retains a peg. Quantitative easing cannot be deemed a ‘beggar-thy-neighbour’ policy as long as the Fed’s policy is geared towards price stability. Current US inflationary expectations are at historically low levels. Central banks should come to an agreement about the definition of price stability at a time of deflationary pressures. The euro’s exchange rate has not been greatly impacted by the recent currency war; the euro continues to be overvalued, but less than before.

Kiigazítás recesszió nélkül. Esettanulmány a magyar stabilizációról = Adjustment without recession: A Case Study of Hungarian Stabilization

1995. március 12-én a magyar kormány és a központi bank szigorú kiigazítási és stabilizációs programot hirdetett meg. A cikk az első eredmények számbavételére tesz kísérletet. A program meghirdetése előtt Magyarország két egymást követő év- ben hatalmas fizetésimérleg-hiányt mutatott fel, és nemzetközi megítélése romlani kezdett. A program radikális intézkedései nyomán elkerülhetővé vált a mexikói vál- sághoz hasonló pénzügyi katasztrófa. Sok makrogazdasági mutató jól érzékelhető javulást jelez: lényegesen csökkent a kereskedelmi mérleg és a folyó fizetési mérleg hiánya, a költségvetés elsődleges egyenlege pozitív lett. Az ilyesféle stabilizációs programokat rendszerint súlyos visszaesés és a munkanélküliség nagy növekedése kíséri. Magyarország elkerülte ezeket a mellékhatásokat: a GDP drasztikus vissza- esés helyett valamelyest tovább növekedett, és a munkanélküliség változatlan ma- radt. A javulásnak nagy ára volt: az életszínvonal erőteljes csökkenése, az infláció felgyorsulása, bár a magyarországi infláció még mindig a kézben tartott, mérsékelt infláció sávjában maradt. A cikk ismerteti a program heterodox módszereit: 1. nagy leértékelés, az előre meghirdetett csúszó árfolyam rezsimjének bevezetése, valamint ideiglenes import- vámpótlék kivetése; 2. határozott jövedelempolitika, amely 12 százalékos reálbércsök- kenést kényszerített ki; 3. fiskális intézkedések, köztük jóléti jogosultságok csök- kentése (a program meghirdetése előtt ezek a jogosultságok tabuk voltak); 4. a hitel- kínálat átcsoportosítása a vállalati szektor javára, a jövedelmezőség növekedése; 5. feszített (bár nem mértéktelenül feszített) monetáris politika, amely lehetővé tette a sikeres vállalatok expanzióját; 6. a privatizáció felgyorsítása, nagy és sikeres lépé- sek egyes kulcsszektorok (energia, telekommunikáció) privatizációjában. Végezetül a tanulmány óva int a túlzott magabiztosságtól és felhívja a figyelmet a potenciális veszélyekre. A makrogazdasági javulás még törékeny. A magyar fejlődés legbiztatóbb sajátossága a termelékenység erőteljes és folyamatos növekedése. / === / On March 12, 1995 Hungary s government and central bank announced a tough program of adjustment and stabilization. This study is an attempt to asses the first results. Before the announcement of the program Hungary had a huge current account deficit for two consecutive years, and her international reputation started to decline. The program s radical measures made it possible to avoid a Mexico-style financial catastrophe. Many macroeconomic indicators show tangible improvement: the trade deficit and the deficit on the current account have been reduced significantly, the primary budget shifted to surplus. These kinds of adjustment programs are usually associated with deep recession and a large increase of unemployment. Hungary avoided these adverse side-effects: GDP instead of a drastic decline, continued to grow somewhat, and unemployment remained unchanged. There was a high price for the improvement: a sharp decline in the standard of living, and an acceleration of inflation, although Hungary is still in the range of controlled, moderate inflation. The paper describes the heterodox instruments of the program: (1) large devaluation, followed by a new exchange rate regime of pre-announced crawling peg, and a temporary import surcharge, (2) energetic income policy, enforcing a 12% cut in real wages; (3) fiscal measures, including cuts in welfare entitlements. That happened for the first time: before the program entitlements had been regarded as taboo ; (4) reallocation of credit supply in favor of the enterprise sector; increase of profitability; (5) tight (but not excessively tight) monetary policy, allowing the expansion of successful private busi- ness; (6) acceleration of privatisation, including large and successful steps in the privatisation of some key sectors (energy, telecommunication). Finally the paper warns against excessive self- confidence and draws the attention to potential dangers. The macroeconomic improvement is still fragile. The most reassuring feature of Hungary s development is the impressive and persistent improvement of productivity.

Inflation, currency substitution and dollarization: The case of Argentina

This dissertation discusses the relationship between inflation, currency substitution and dollarization that has taken place in Argentina for the past several decades.^ First, it is shown that when consumers are able to hold only domestic monetary balances (without capital mobility) an increase in the rate of inflation will produce a balance of payments deficit. We then look at the same issue but with heterogeneous consumers, this heterogeneity being generated by non-proportional lump-sum transfers.^ Second, we discussed some necessary assumptions related to currency substitution models and concluded that there was no a-priori conclusion on whether currencies should be assumed to be "cooperant" or "non-cooperant" in utility. That is to say, whether individuals held different currencies together or one instead of the other.^ Third, we went into discussing the issue of currency substitution as being a constraint on governments' inflationary objectives rather than a choice of those governments to avoid hyperinflations. We showed that imperfect substitutability between currencies does not "reduce the scope for rational (hyper)inflationary processes" as it had been previously argued. It will ultimately depend on the parametrization used and not on the intrinsic characteristics of imperfect substitutability between currencies.^ We further showed that in Argentina, individuals have been able to endogenize the money supply by holding foreign monetary balances. We argued that the decision to hold foreign monetary balances by individuals is always a second best due to the trade-off between holding foreign monetary balances and consumption. For some levels of income, consumption, and foreign inflation, individuals would prefer to hold domestic monetary balances rather than foreign ones.^ We then modeled the distinction between dollarization and currency substitution. We concluded that although dollarization is necessary for currency substitution to take place, the decision to use foreign monetary balances for transactions purposes is largely independent from the dollarization process.^ Finally, we concluded that Argentina should not fully dollarize its economy because dollarization is always a second best to using a domestic currency. Further, we argued that a fixed exchange system would be better than a flexible exchange rate or a "crawling-peg" system because of the characteristics of the political system and the possibilities of "mass praetorianism" to develop, which is intricately linked to "populist" solutions. ^

An evaluation of exchange rate policy and economic adjustment in Nicaragua, 1993--1995

Since the late 1970's, but particularly since the mid-1980s, the economy of Nicaragua has had persistent and large macroeconomic imbalances, while GDP per-capita has declined to 1950s' levels. By the second half of the 1990s, huge fiscal deficits and a reduction of foreign financing resulted in record hyperinflation. The Sandinista government's (1979–1990) harsh stabilization program in 1988–89 had only modest and short-lived success. It was doomed by their inability to lower the public sector deficit due to the war, plus diminishing financial support from abroad. Hyperinflation stopped only after their 1990 electoral defeat ended the war and massive aid began to flow in. Five years later, macroeconomic stability is still very fragile. A sluggish recovery of export agriculture plus import liberalization, have impeded a reduction of huge trade and current account deficits. Facing the prospects of diminished aid flows, the government's strategy has hinged on the achievement of a real devaluation through a crawling-peg adjustment of the nominal rate. However, at the end of 1995 the situation of the external accounts was still critical, and the modest progress achieved was attributable to cyclical terms-of-trade improvement and changes in the political outlook of agricultural producers. Using a Computable General Equilibrium Model and a Social Accounting Matrix constructed for this dissertation, the importance of structural rigidities in production and demand in explaining such outcome is shown. It is shown that under the plausible structural assumptions incorporated in the model, the role of devaluation in the adjustment process is restricted by structural rigidities. Moreover, contrary to the premise of the orthodox economic thinking behind the economic program, it is the contractionary effect of devaluation more than its expenditure-switching effects that provide the basis for is use in solving the external sector's problems. A fixed nominal exchange rate is found to lead to adverse results. The broader conclusion that emerges from the study is that a new social compact and a rapid increase in infrastructure spending plus fiscal support for the traditional agro-export activities is at the center of a successful adjustment towards external viability in Nicaragua. ^

Controlled growth of carbon nanotubes for high performance nanoelectronics

Unique electrical and mechanical properties of single-walled carbon nanotubes (SWNTs) have made them one of the most promising candidates for next-generation nanoelectronics. Efficient utilization of the exceptional properties of SWNTs requires controlling their growth direction (e.g., vertical, horizontal) and morphologies (e.g., straight, junction, coiled). ^ In this dissertation, the catalytic effect on the branching of SWNTs, Y-shaped SWNTs (Y-SWNTs), was investigated. The formation of Y-shaped branches was found to be dependent on the composition of the catalysts. Easier carbide formers have a strong tendency to attach to the sidewall of SWNTs and thus enhance the degree of branching. Y-SWNTs based field-effect transistors (FETs) were fabricated and modulated by the metallic branch of the Y-SWNTs, exhibiting ambipolar characteristics at room temperature. A subthreshold swing of 700 mV/decade and an on/off ratio of 105 with a low off-state current of 10-13 A were obtained. The transport phenomena associated with Y- and cross-junction configurations reveals that the conduction mechanism in the SWNT junctions is governed by thermionic emission at T > 100 K and by tunneling at T < 100 K. ^ Furthermore, horizontally aligned SWNTs were synthesized by the controlled modification of external fields and forces. High performance carbon nanotube FETs and logic circuit were demonstrated utilizing the aligned SWNTs. It is found that the hysteresis in CNTFETs can be eliminated by removing absorbed water molecules on the CNT/SiO2 interface by vacuum annealing, hydrophobic surface treatment, and surface passivation. SWNT “serpentines” were synthesized by utilization of the interaction between drag force from gas flow and Van der Waals force with substrates. The curvature of bent SWNTs could be tailored by adjusting the gas flow rate, and changing the gas flow direction with respect to the step-edges on a single-crystal quartz substrate. Resistivity of bent SWNTs was observed to increase with curvature, which can be attributed to local deformations and possible chirality shift at curved part. ^ Our results show the successful synthesis of SWNTs having controllable morphologies and directionality. The capability of tailoring the electrical properties of SWNTs makes it possible to build an all-nanotube device by integrating SWNTs, having different functionalities, into complex circuits. ^

Functionalized carbon nanotube nanoelectrodes for biomolecular recognition

The objective of this research is to develop nanoscale ultrasensitive transducers for detection of biological species at molecular level using carbon nanotubes as nanoelectrodes. Rapid detection of ultra low concentration or even single DNA molecules are essential for medical diagnosis and treatment, pharmaceutical applications, gene sequencing as well as forensic analysis. Here the use of functionalized single walled carbon nanotubes (SWNT) as nanoscale detection platform for rapid detection of single DNA molecules is demonstrated. The detection principle is based on obtaining electrical signal from a single amine terminated DNA molecule which is covalently bridged between two ends of an SWNT separated by a nanoscale gap. The synthesis, fabrication, chemical functionalization of nanoelectrodes and DNA attachment were optimized to perform reliable electrical characterization these molecules. Using this detection system fundamental study on charge transport in DNA molecule of both genomic and non genomic sequences is performed. We measured an electrical signal of about 30 pA through a hybridized DNA molecule of 80 base pair in length which encodes a portion of sequence of H5N1 gene of avian Influenza A virus. Due the dynamic nature of the DNA molecules the local environment such as ion concentration, pH and temperature significantly influence its physical properties. We observed a decrease in DNA conductance of about 33% in high vacuum conditions. The counterion variation was analyzed by changing the buffer from sodium acetate to tris(hydroxymethyl) aminomethane, which resulted in a two orders of magnitude increase in the conductivity of the DNA. The fabrication of large array of identical SWNT nanoelectrodes was achieved by using ultralong SWNTs. Using these nanoelectrode array we have investigated the sequence dependent charge transport in DNA. A systematic study performed on PolyG - PolyC sequence with varying number of intervening PolyA - PolyT pairs showed a decrease in electrical signal from 180 pA (PolyG - PolyC) to 30 pA with increasing number of the PolyA - PolyT pairs. This work also led to the development of ultrasensitive nanoelectrodes based on enzyme functionalized vertically aligned high density multiwalled CNTs for electrochemical detection of cholesterol. The nanoelectrodes exhibited selectively detection of cholesterol in the presence of common interferents found in human blood.

Inflation, currency substitution, and dollarization : the case of Argentina

This dissertation discusses the relationship between inflation, currency substitution and dollarization that has taken place in Argentina for the past several decades. First, it is shown that when consumers are able to hold only domestic monetary balances (without capital mobility) an increase in the rate of inflation will produce a balance of payments deficit. We then look at the same issue but with heterogeneous consumers, this heterogeneity being generated by non-proportional lump-sum transfers. Second, we discussed some necessary assumptions related to currency substitution models and concluded that there was no a-priori conclusion on whether currencies should be assumed to be "cooperant" or "non-cooperant" in utility. That is to say, whether individuals held different currencies together or one instead of the other. Third, we went into discussing the issue of currency substitution as being a constraint on governments inflationary objectives rather than a choice of those governments to avoid hyperinflations. We showed that imperfect substitutability between currencies does not "reduce the scope for rational (hyper)inflationary processes" as it had been previously argued. It will ultimately depend on the parametrization used and not on the intrinsic characteristics of imperfect substitutability between currencies. We further showed that in Argentina, individuals have been able to endogenize the money supply by holding foreign monetary balances. We argued that the decision to hold foreign monetary balances by individuals is always a second best due to the trade-off between holding foreign monetary balances and consumption. For some levels of income, consumption, and foreign inflation, individuals would prefer to hold domestic monetary balances rather than foreign ones. We then modeled the distinction between dollarization and currency substitution. We concluded that although dollarization is necessary for currency substitution to take place, the decision to use foreign monetary balances for transactions purposes is largely independent from the dollarization process. Finally, we concluded that Argentina should not fully dollarize its economy because dollarization is always a second best to using a domestic currency. Further, we argued that a fixed exchange system would be better than a flexible exchange rate or a "crawling-peg" system because of the characteristics of the political system and the possibilities of "mass praetorianism" to develop, which is intricately linked to "populist" solutions.

Highly stable PEGylated gold nanoparticles in water: applications in biology and catalysis

Gold nanoparticles (Au NPs) with diameters ranging between 5-60 nm have been synthesised in water, and further stabilized with polyethylene glycol-based thiol polymers (mPEG-SH). Successful PEGylation of the Au NPs was confirmed by Dynamic Light scattering (DLS) and Zeta potential measurements. PEG coating of the Au NPs is the key of their colloidal stabilty, and its successful applications. Catalytic efficiency testing of the PEG-AuNPs were carried out on homocoupling of boronic acid. PEG-Au NPs with AuNps diameter < 30 nm were useful as catalyst in water. Finally, the PEG-Au NPs were also shown to be stable in biological fluid and not cytotoxic on B16.F10 cell line, making them attractive for further studies.