Application and use of isothermal calorimetry in pharmaceutical development

There are many steps involved in developing a drug candidate into a formulated medicine and many involve analysis of chemical interaction or physical change. Calorimetry is particularly suited to such analyses as it offers the capacity to observe and quantify both chemical and physical changes in virtually any sample. Differential scanning calorimetry (DSC) is ubiquitous in pharmaceutical development, but the related technique of isothermal calorimetry (IC) is complementary and can be used to investigate a range of processes not amenable to analysis by DSC. Typically, IC is used for longer-term stability indicating or excipient compatibility assays because both the temperature and relative humidity (RH) in the sample ampoule can be controlled. However, instrument design and configuration, such as titration, gas perfusion or ampoule-breaking (solution) calorimetry, allow quantification of more specific values, such as binding enthalpies, heats of solution and quantification of amorphous content. As ever, instrument selection, experiment design and sample preparation are critical to ensuring the relevance of any data recorded. This article reviews the use of isothermal, titration, gas-perfusion and solution calorimetry in the context of pharmaceutical development, with a focus on instrument and experimental design factors, highlighted with examples from the recent literature. © 2011 Elsevier B.V.

Multi-threaded parallel simulation of non-local non-linear problems in ultrashort laser pulse propagation in the presence of plasma

We describe a parallel multi-threaded approach for high performance modelling of wide class of phenomena in ultrafast nonlinear optics. Specific implementation has been performed using the highly parallel capabilities of a programmable graphics processor. © 2011 SPIE.

Localized surface plasmon fiber device coated with carbon nanotubes for the specific detection of CO2

We explored the potential of a carbon nanotube (CNT) coating working in conjunction with a recently developed localized surface plasmon (LSP) device (based upon a nanostructured thin film consisting of of nano-wires of platinum) with ultra-high sensitivity to changes in the surrounding index. The uncoated LSP sensor’s transmission resonances exhibited a refractive index sensitivity of Δλ/Δn ~ -6200nm/RIU and ΔΙ/Δn ~5900dB/RIU, which is the highest reported spectral sensitivity of a fiber optic sensor to bulk index changes within the gas regime. The complete device provides the first demonstration of the chemically specific gas sensing capabilities of CNTs utilizing their optical characteristics. This is proven by investigating the spectral response of the sensor before and after the adhesion of CNTs to alkane gases along with carbon dioxide. The device shows a distinctive spectral response in the presence of gaseous CO2 over and above what is expected from general changes in the bulk refractive index. This fiber device yielded a limit of detection of 150ppm for CO2 at a pressure of one atmosphere. Additionally the adhered CNTs actually reduce sensitivity of the device to changes in bulk refractive index of the surrounding medium. The polarization properties of the LSP sensor resonances are also investigated and it is shown that there is a reduction in the overall azimuthal polarization after the CNTs are applied. These optical devices offer a way of exploiting optically the chemical selectivity of carbon nanotubes, thus providing the potential for real-world applications in gas sensing in many inflammable and explosive environments. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Cell-specific effects of Nox2 on the acute and chronic response to myocardial infarction

BACKGROUND: Increased reactive oxygen species (ROS) production is involved in the process of adverse cardiac remodeling and development of heart failure after myocardial infarction (MI). NADPH oxidase-2 (Nox2) is a major ROS source within the heart and its activity increases after MI. Furthermore, genetic deletion of Nox2 is protective against post-MI cardiac remodeling. Nox2 levels may increase both in cardiomyocytes and endothelial cells and recent studies indicate cell-specific effects of Nox2, but it is not known which of these cell types is important in post-MI remodeling. METHODS AND RESULTS: We have generated transgenic mouse models in which Nox2 expression is targeted either to cardiomyocytes (cardio-Nox2TG) or endothelial cells (endo-Nox2TG). We here studied the response of cardio-Nox2TG mice, endo-Nox2TG mice and matched wild-type littermates (WT) to MI induced by permanent left coronary artery ligation up to 4weeks. Initial infarct size assessed by magnetic resonance imaging (MRI) and cardiac dysfunction were similar among groups. Cardiomyocyte hypertrophy and interstitial fibrosis were augmented in cardio-Nox2TG compared to WT after MI and post-MI survival tended to be worse whereas endo-Nox2TG mice showed no significant difference compared to WT. CONCLUSIONS: These results indicate that cardiomyocyte rather than endothelial cell Nox2 may have the more important role in post-MI remodeling.

A kapitalizmus néhány rendszerspecifikus vonása (Some system-specific features of capitalism)

A szerző korábban a szocialista rendszer és a posztszocialista átmenet elemzésére használta azt a szemléletet és módszertant, amelyet rendszerparadigmának nevezett el. A jelen tanulmány a kapitalizmus néhány általános vonásának vizsgálatára alkalmazza ezt a megközelítést. A cikk - fogalmi tisztázás után - példákat sorol fel a kapitalizmus néhány rendszerspecifikus vonására, majd kettővel részletesebben foglalkozik. Az egyik: a rendszer dinamizmusa. Az elmúlt évszázad nagy újításai, amelyek mélyrehatóan átalakították nemcsak a termelés technológiáját, hanem az emberek mindennapi életét is, a kapitalista rendszer és annak főszereplője, a vállalkozó vezette be és terjesztette el. Csak a kapitalizmusban tud kialakulni a vállalkozás és újítás mechanizmusa, az ehhez szükséges erőteljes ösztönzés és rugalmas tőkepiac. A másik példa: a kapitalista rendszer immanens tulajdonsága a munkaerőpiacon jelentkező tartós többlet, szemben a szocialista rendszerrel, amelynek kifejlett formájában tartós munkaerőhiány mutatkozik. Elméletileg és tapasztalatilag is igazolható, hogy minél dinamikusabb a kapitalista gazdaság állandó átalakulása, annál inkább keletkezik strukturális munkanélküliség. A hatékony bér elmélete megmagyarázza, miért érdeke a munkaadónak, hogy a piactisztító bérnél magasabb bért fizessen, és ezzel munkanélküliséget idézzen elő. A kapitalizmus reformálható rendszer. Ám ügyelni kell arra, hogy a részreformok között milyen a kapcsolat. Szerencsés esetben kiegészítik egymást. Ám ennél sokkal gyakoribb, hogy miközben szembeszállunk a rendszer egyik kedvezőtlen hajlamával, utat engedünk egy másik kedvezőtlen hajlam megerősödésének. ___________________ The author previously applied the outlook and methodology he named the system paradigm to analysing the socialist system and post-socialist transition. This study takes the same approach to some general attributes of capitalism. After clarifying some concepts, the author presents examples of some system-specific features of capitalism, before ad-dressing two of them in detail. One is the dynamism of the system. The great innovations of the last century that radically altered both the technology of production and people s daily lives were all introduced and disseminated by the capitalist system and its protago-nist, the entrepreneur. Only under capitalism can the mechanism of entrepreneurship and innovation emerge, with the strong incentives and flexible capital market they require. The other immanent feature is a chronic surplus on the labour market that contrasts sharply with the chronic labour shortage prevalent under the mature socialist system. Theory and experience confirm that the faster the ongoing transformation of a capitalist economy proceeds, the greater the propensity for structural unemployment to appear. It is explained by the efficiency pay hypothesis how an employer has an incentive to pay more than a market-clearing wage, thereby introducing unemployment. Capitalism is a system that can be reformed, but attention needs paying to relations between reforms of different parts of the system. In fortunate cases they complement each other, but it is commoner to find that tackling one unfavourable tendency only allows another such tendency to increase.

Hirschman meets Williamson: Relationship-specific investment and loyalty

In Albert Hirschman’s theory, loyalty plays a key role in the equilibrium between exit and voice. This article extends economic (rational choice) analysis to the emergence of loyalty, which Hirschman considers an exogenous factor. This is accomplished by linking Williamson’s theory of specific investment to Hirschman’s model. Three cases are distinguished: (1) loyalty is due to specific investment; (2) loyalty is due to (intermediate) factors influenced by specific investment; and, (3) loyalty is independent of specific investment. A simple model formalizes the first case. A paradoxical dynamic of loyalty is identified: a lower degree of specificity may lead to a weakening of loyalty in the short run but astrengthening of loyalty in the long run. An application to the process of European integration is sketched.