Differential scanning calorimetry in life science: thermodynamics, stability, molecular recognition and application in drug design

All biological phenomena depend on molecular recognition, which is either intermolecular like in ligand binding to a macromolecule or intramolecular like in protein folding. As a result, understanding the relationship between the structure of proteins and the energetics of their stability and binding with others (bio)molecules is a very interesting point in biochemistry and biotechnology. It is essential to the engineering of stable proteins and to the structure-based design of pharmaceutical ligands. The parameter generally used to characterize the stability of a system (the folded and unfolded state of the protein for example) is the equilibrium constant (K) or the free energy (deltaG(o)), which is the sum of enthalpic (deltaH(o)) and entropic (deltaS(o)) terms. These parameters are temperature dependent through the heat capacity change (deltaCp). The thermodynamic parameters deltaH(o) and deltaCp can be derived from spectroscopic experiments, using the van't Hoff method, or measured directly using calorimetry. Along with isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) is a powerful method, less described than ITC, for measuring directly the thermodynamic parameters which characterize biomolecules. In this article, we summarize the principal thermodynamics parameters, describe the DSC approach and review some systems to which it has been applied. DSC is much used for the study of the stability and the folding of biomolecules, but it can also be applied in order to understand biomolecular interactions and can thus be an interesting technique in the process of drug design.

Expression of the Ets transcription factor Erm is regulated through a conventional PKC signaling pathway in the Molt4 lymphoblastic cell line.

Erm, a member of the PEA3 group within the Ets family of transcription factors, is expressed in murine and human lymphocytes. Here, we show that in the human Molt4 lymphoblastic cell line, the erm gene expression is regulated by the conventional PKC (cPKC) pathway. To better characterize the molecular mechanism by which cPKC regulates Erm transcription in Molt4 cells, we tested proximal promoter deletions of the human gene, and identified a specific cPKC-regulated region between positions -420 and -115 upstream of the first exon.

1960-1980. Het gouden tijdperk van de openbare werken. 1960-1980. L'âge d'or des travaux public

info:eu-repo/semantics/published

12C2H2-Ar van der Waals complex

New theoretical and experimental results on the acetylene-Ar van der Waals complex are presented and the literature is reviewed. New ab initio calculations at the MP2 level were performed using large basis sets with diffuse functions and taking into account the basis set superposition error. It was found that the structure of acetylene is not significantly altered by the complexation and that its vibrational frequencies are only slightly lowered. Finally, it was observed that the calculated properties of the complex (structure, vibrational spectrum, bond dissociation energy) are not sensitive to the structure imposed on acetylene. Experimentally, acetylene-Ar was produced in a supersonic expansion under experimental conditions corresponding to 9 K rotational temperature. Thanks to the performances of CW-CRDS detection, the Ka = 0 ← 1, 1 ← 0, and 2 ← 1 sub- bands of the v1 + v3 band could be recorded and resolved and most of their lines assigned. Upper-state rotational constants were fitted, however not including the upper Ka = 2 state, which shows K-doubling the opposite of the expected. The Lorentzian width of most line profiles sets the mean lifetime to some 7.5 ns. Local perturbations affecting line positions and/or line widths are demonstrated. Additional series of lines tentatively attributed to acetylene-Ar are discussed.© 2009 American Chemical Society.

Accurate ground-state potential energy surfaces of the C2H2–Kr and C2H2–Xe van der Waals complexes

Accurate ab initio intermolecular potential energy surfaces (IPES) have been obtained for the first time for the ground electronic state of the C 2H2-Kr and C2H2-Xe van der Waals complexes. Extensive tests, including complete basis set and all-electron scalar relativistic results, support their calculation at the CCSD(T) level of theory, using small-core relativistic pseudopotentials for the rare-gas atoms and aug-cc-pVQZ basis sets extended with a set of 3s3p2d1f1g mid-bond functions. All results are corrected for the basis set superposition error. The importance of the scalar relativistic and rare-gas outer-core (n.1)d correlation effects is investigated. The calculated IPES, adjusted to analytical functions, are characterized by global minima corresponding to skew T-shaped geometries, in which the Jacobi vector positioning the rare-gas atom with respect to the center of mass of the C2H2 moiety corresponds to distances of 4.064 and 4.229Å, and angles of 65.22° and 68.67° for C 2H2-Kr and C2H2-Xe, respectively. The interaction energy of both complexes is estimated to be -151.88 (1.817 kJ mol-1) and -182.76 cm-1 (2.186 kJ mol-1), respectively. The evolution of the topology of the IPES as a function of the rare-gas atom, from He to Xe, is also discussed. © 2012 Taylor and Francis.

Patent litigation in Europe

We compare patent litigation cases across four European jurisdictions – Germany, France, the Netherlands, and the UK – covering cases filed during the period 2000-2008. For our analysis, we assemble a new dataset that contains detailed information at the case, litigant, and patent level for patent cases filed at the major courts in the four jurisdictions. We find substantial differences across jurisdictions in terms of case loads. Courts in Germany hear by far the largest number of cases in absolute terms, but also when taking country size into account. We also find important between-country differences in terms of outcomes, the share of cases that is appealed, as well as the characteristics of litigants and litigated patents. A considerable number of patents are litigated in multiple jurisdictions, but the majority of patents are subject to litigation only in one of the four jurisdictions.

Absolute line intensities for formic acid and dissociation constant of the dimer

Absolute line intensities in the v6 and v8 interacting bands of trans-HCOOH, observed near 1105.4 and 1033.5 cm -1, respectively, and the dissociation constant of the formic acid dimer (HCOOH)2 have been measured using Fourier transform spectroscopy at a resolution of 0.002 cm-1. Eleven spectra of formic acid, at 296.0(5) K and pressures ranging from 14.28(25) to 314.0(24) Pa, have been recorded between 600 and 1900 cm-1 with an absorption path length of 19.7(2) cm. 437 integrated absorption coefficients have been measured for 72 lines in the v6 band. Analysis of the pressure dependence yielded the dissociation constant of the formic acid dimer, k p=361(45) Pa, and the absolute intensity of the 72 lines of HCOOH. The accuracy of these results was carefully estimated. The absolute intensities of four lines of the weak v8 band were also measured. Using an appropriate theory, the integrated intensity of the v6 and v 8 bands was determined to be 3.47 × 1017 and 4.68 × 10-19 cm-1/(molecule cm-1) respectively, at 296 K. Both the dissociation constant and integrated intensities were compared to earlier measurements. © 2007 American Institute of Physics.

La elipse como lugar geométrico a través de la geometría del doblado de papel en el contexto de Van Hiele

El presente artículo es un producto derivado de la investigación: “La elipse como lugar geométrico a través de la geometría del doblado de papel en el contexto de Van Hiele”, en la que se analizó el proceso de comprensión del concepto de elipse como lugar geométrico, de cinco estudiantes del grado décimo de una Institución Educativa de la ciudad de Medellín. El estudio de casos cualitativo permitió el establecimiento de los descriptores de los niveles de razonamiento de Van Hiele que caracterizaron dicho proceso de comprensión y a su vez, iluminaron la creación de un guion de entrevista de carácter socrático, que se convirtió en una experiencia de aprendizaje para los estudiantes en tanto que les permitió avanzar en su nivel de razonamiento.

Fases de aprendizaje en el contexto de van Hiele para el concepto de continuidad local

El presente reporte articula el modelo educativo de van Hiele en su aspecto prescriptivo con la enseñanza de uno de los conceptos fundamentales del Análisis Matemático, continuidad local, a través de la implementación y el desarrollo de un Módulo de Aprendizaje que permite procesos de razonamiento en los estudiantes con el fin de promoverlos de un Nivel II a un Nivel III, el módulo es construido en correspondencia con los descriptores de fases para de dar cuenta de las estructuras mentales elaboradas. Posteriormente, en el análisis de cada uno de los tres casos, se describe en categorías en correspondencia los descriptores y donde se hace explícito como razonan los estudiantes en su paso del Nivel II al Nivel III respecto al concepto de continuidad local.

Determinación de niveles Van Hiele en alumnos de primer año medio sobre la transformación isométrica de simetría

Este artículo presenta los resultados de una investigación realizada en alumnos de primer año medio del Liceo Eleuterio Ramírez de Osorno. El objetivo de dicha investigación era conocer el desarrollo del pensamiento geométrico en el tema de transformaciones isométricas según la Teoría de Van Hiele. La metodología de investigación es cualitativa, específicamente mediante estudio de casos. La recolección de datos se realizó mediante un seguimiento en el desarrollo de las actividades planteadas, observación de participantes y entrevistas. Como resultado se obtuvo que los alumnos mayoritariamente exhiben características del nivel 1 de reconocimiento para la isometría de simetría.

Aspectos comparativos en la extensión del modelo de Van Hiele al concepto de aproximación local

En el contexto del modelo de Van Hiele, se ha llevado a cabo un estudio comparativo de dos colecciones de descriptores para el mismo concepto: El de aproximación local en su manifestación de la recta tangente a la gráfica de una curva en un punto. A partir de las visualizaciones que se obtienen de los mecanismos llamados "haz de secantes" y del "zoom", se concluye que, en efecto, el nivel de razonamiento es independiente de la forma de abordar el concepto, de ese mecanismo particular usado para acercarse al mismo.

Two simple constant ratio approximation algorithms for minimizing the total weighted completion time on a single machine with a fixed non-availability interval

In this note, we consider the scheduling problem of minimizing the sum of the weighted completion times on a single machine with one non-availability interval on the machine under the non-resumable scenario. Together with a recent 2-approximation algorithm designed by Kacem [I. Kacem, Approximation algorithm for the weighted flow-time minimization on a single machine with a fixed non-availability interval, Computers & Industrial Engineering 54 (2008) 401–410], this paper is the first successful attempt to develop a constant ratio approximation algorithm for this problem. We present two approaches to designing such an algorithm. Our best algorithm guarantees a worst-case performance ratio of 2+ε. © 2008 Elsevier B.V. All rights reserved.

Debating the division of labour in healthcare in France and England

As Larson (1990) states, professions are historically specific and ‘there is no pattern of social closure around an occupation that is not inflected by the latter’s past, its specific activity and typical context of performance or…the political context in which closure is obtained.’ Larson’s work focuses particularly on the differences between the establishment of professions in France, where there was considerable state intervention, with that in the US and UK, both of which were more market-oriented. This paper is based on data from an evaluation of a large European exchange programme of staff between Kent and Lille, from 2005 to 2008 and discusses the division of labour in healthcare between two occupational groups, medicine and nursing, in England and in France. This division of labour has been extensively discussed in the UK, particularly since from the mid 1990s the nursing role has been extended and innovations such as nurse prescribing have been introduced, whereas such extended roles have not been introduced in France. The paper draws particularly on interview data from mental health practitioners, in which it is argued that whilst the English nurses may on the surface seem to have a wider range of competences and autonomy, in reality they are more constrained, as they operate under protocols and therefore do not exercise professional judgement. Not only do these data illustrate the centrality of professional judgement in discussions about practice, they also demonstrate the circularity of many debates on extended roles.

Sediment transfer and accumulation in two contrasting salt marsh/mudflat systems: the Seine estuary (France) and the Medway estuary (UK)

Understanding the dynamics of fine sediment transport across the upper intertidal zone is critical in managing the erosion and accretion of intertidal areas, and in managed realignment/estuarine habitat recreation strategies. This paper examines the transfer of sediments between salt marsh and mudflat environments in two contrasting macrotidal estuaries: the Seine (France) and the Medway (UK), using data collected during two joint field seasons undertaken by the Anglo-French RIMEW project (Rives-Manche Estuary Watch). High-resolution ADCP, Altimeter, OBS and ASM measurements from mudflat and marsh surface environments have been combined with sediment trap data to examine short-term sediment transport processes under spring tide and storm flow conditions. In addition, the longer-term accumulation of sediment in each salt marsh system has been examined via radiometric dating of sediment cores. In the Seine, rapid sediment accumulation and expansion of salt marsh areas, and subsequent loss of open intertidal mudflats, is a major problem, and the data collected here indicate a distinct net landward flux of sediments into the marsh interior. Suspended sediment fluxes are much higher than in the Medway estuary (averaging 0.09 g/m(3)/s), and vertical accumulation rates at the salt marsh/mudflat boundary exceed 3 cm/y. Suspended sediment data collected during storm surge conditions indicate that significant in-wash of fine sediments into the marsh interior can occur during (and following) these high-magnitude events. In contrast to the Seine, the Medway is undergoing erosion and general loss of salt marsh areas. Suspended sediment fluxes are of the order of 0.03 g/m(3)/s, and the marsh system here has much lower rates of vertical accretion (sediment accumulation rates are ca. 4 mm/y). Current velocity data for the Medway site indicate higher velocities on the ebb tide than occur on the flood tide, which may be sufficient to remobilise sediments deposited on the previous tide and so force net removal of material from the marsh.