Vibrational spectroscopy and DFT calculations of the di-amino acid peptide L-aspartyl-L-glutamic acid in the zwitterionic state

Solid state IR and Raman as well as aqueous solution state Raman spectra are reported for the linear di-amino acid peptide L-aspartyl-L-glutamic acid (L-Asp-L-Glu); the solution state Raman spectrum has also been obtained for the N,O-deuterated derivative. SCF-DFT calculations at the B3-LYP/cc-pVDZ level established that the structure and vibrational spectra of L-Asp-L-Glu can be interpreted using a model of the peptide with ten hydrogen-bonded water molecules, in conjunction with the conductor-like polarizable continuum solvation method. The DFT calculations resulted in the computation of a stable zwitterionic structure, which displays trans-amide conformation. The vibrational spectra were computed at the optimised molecular geometry, enabling normal coordinate analysis, which yielded satisfactory agreement with the experimental IR and Raman data. Computed potential energy distributions of the normal modes provided detailed vibrational assignments.

Performance measurement and benchmarking of a major innovation programme

Purpose: The purpose of this paper is to describe the problems encountered and the solutions developed when using benchmarking and key performance indicators (KPIs) to monitor a major UK social house building innovation (change) programme. The innovation programme sought improvements to both the quality of the house product and the procurement process. Design/methodology/approach: Benchmarking and KPIs were used to quantify performance and in-depth case studies to identify underlying cause and effect relationships within the innovation programme. Findings: The inherent competition between consortium members; the complexity of the relationship between the consortium and its strategic partner; the lack of an authoritative management control structure; and the rapidly changing nature of the UK social housing market all proved problematic to the development of a reliable and robust monitoring system. These problems were overcome by the development of multi-dimensional benchmarking model that balanced the needs and aspirations of the individual organisations with the broader objectives of the consortium. Research limitations/implications: Whilst the research methodology provides insight into the factors that affected the performance of a major innovation programme its findings may not be representative of all projects. Practical implications: The lessons learnt should assist those developing benchmarking models for multi-client consortia. Originality/value: The work reported in this paper describes an inclusive approach to benchmarking in which a multiple client group and their strategic partner sought to work together for shared gain. Very few papers have addressed this issue.

Contratos públicos adjudicados a sociedades cooperativas en el País Vasco entre 2010 y 2012

La Contratación Pública constituye una fuente muy importante de la demanda de bienes y servicios, especialmente en la Comunidad Autónoma del País Vasco en donde el Gobierno Autonómico, también llamado la Administración General Vasca, desarrolla un papel capital como impulsor de dicha contratación pública. Por otro lado, la Economía Social, y especialmente el movimiento cooperativo, tiene en ese mismo ámbito geográfico un papel de gran peso en el conjunto de la Economía Vasca, por sus cifras de empleo y aportación al PIB, así como por tradición y arraigo social. Cabe preguntarse en tal caso, cuál es el papel que desempeñan las cooperativas en la Contratación Pública en aquella Comunidad Autónoma, cómo y cuáles son los contratos de los que resultan adjudicatarias, qué importes suponen esos contratos para las cuentas públicas y, en definitiva, si su papel de adjudicatarias se corresponde con el que desempeñan en el conjunto de la Economía Vasca. Del examen de los contratos publicados en el Perfil del Contratante del Gobierno Vasco, se obtienen datos suficientes que, una vez procesados y analizados, se visualizan en tablas y porcentajes que constituyen la base de un diagnóstico que responde a las preguntas planteadas y evidencia la situación de debilidad de las cooperativas en el campo de la contratación pública vasca.

Photoelectron Imaging Following 2 þ 1 Multiphoton Excitation of HBr

The photodissociation and photoionization dynamics of HBr via low-n Rydberg and ion-pair states was studied by using 2 + 1 REMPI spectroscopy and velocity map imaging of photoelectrons. Two-photon excitation at about 9.4–10 eV was used to prepare rotationally selected excited states. Following absorption of the third photon the unperturbed F 1Δ(2) and i 3Δ(2) states ionize directly into the ground vibrational state of the molecular ion according to the Franck–Condon principle and upon preservation of the ion core. In case of the V 1Σ+(0+) ion-pair state and the perturbed E 1Σ+(0+), g 3Σ−(0+), and H 1Σ+(0+) Rydberg states the absorption of the third photon additionally results in a long vibrational progression of HBr+ in the X 2Π state as well as formation of electronically excited atomic photofragments. The vibrational excitation of the molecular ion is explained by autoionization of repulsive superexcited states into the ground state of the molecular ion. In contrast to HCl, the perturbed Rydberg states of HBr show strong participation of the direct ionization process, with ionic core preservation.

Evaluation of the antiangiogenic potential of AQ4N.

Purpose: A number of cytotoxic chemotherapy agents tested at low concentrations show antiangiogenic properties with limited cytotoxicity, e.g., cyclophosphamide, tirapazamine, and mitoxantrone. AQ4N is a bioreductive alkylaminoanthraquinone that is cytotoxic when reduced to AQ4; hence, it can be used to target hypoxic tumor cells. AQ4N is structurally similar to mitoxantrone and was evaluated for antiangiogenic properties without the need for bioreduction.

Experimental Design:The effect of AQ4N and fumagillin on human microvascular endothelial cells (HMEC-1) was measured using a variety ofin vitro assays, i.e., 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide, wound scrape, tubule formation, rat aortic ring, and invasion assays. Low-dose AQ4N (20 mg/kg) was also given in vivo to mice bearing a tumor in a dorsal skin flap.

Results:AQ4N (10-11to10-5mol/L) hadno effect on HMEC-1viability. AQ4N (10-9to10-5mol/L) caused a sigmoidal dose-dependent inhibition of endothelial cell migration in the wound scrape model. Fumagillin showed a similar response over a lower dose range (10-13 to 10-9 mol/L); however, the maximal inhibition was less (25% versus 43% for AQ4N). AQ4N inhibited HMEC-1 cell contacts on Matrigel (10-8 to 10-5 mol/L), HMEC-1 cell invasion, and sprouting in rat aorta explants. Immunofluorescence staining with tubulin, vimentim, dynein, and phalloidin revealed that AQ4N caused disruption to the cell cytoskeleton. When AQ4N (20 mg/kg) was given in vivo for 5 days, microvessels disappeared in LNCaP tumors grown in a dorsal skin flap.

Conclusions:This combination of assays has shown that AQ4N possesses antiangiogenic effects in normoxic conditions, which could potentially contribute to antitumor activity