101 research outputs found
X-ray crystallographic studies of metalloproteins.
No full textInternational audienceMany proteins require metals for their physiological function. In combination with spectroscopic characterizations, X-ray crystallography is a very powerful method to correlate the function of protein-bound metal sites with their structure. Due to their special X-ray scattering properties, specific metals may be located in metalloprotein structures and eventually used for phasing the diffracted X-rays by the method of Multi-wavelength Anomalous Dispersion (MAD). How this is done is the principle subject of this chapter. Attention is also given to the crystallographic characterization of different oxidation states of redox active metals and to the complication of structural changes that may be induced by X-ray irradiation of protein crystals
Stemple Pass (2012) et le projet Two Cabins : l’architecture de la solitude selon James Benning
No full textLe projet Two Cabins de James Benning gravite autour de la reproduction de deux cabanes dans l’espace de son jardin. La première est celle d’Henry David Thoreau, auteur transcendantaliste de Walden ou La vie dans les bois (1854). La seconde est celle de Theodore Kaczynski, aussi surnommé « Unabomber », écoterroriste états-unien et auteur d’un manifeste antitechnologique. Cet article se penche en particulier sur le film Stemple Pass (Benning, 2012), qui confronte les écrits de Kaczynski à la reproduction de son habitat.James Benning’s project Two Cabins revolves around the reconstruction of two cabins in his own yard (or garden). The first belongs to Henry David Thoreau, the transcendentalist author of Walden; or, Life in the Woods (1854). The second is that of Theodore Kaczynski, an ecoterrorist also known as “the Unabomber” who wrote an anti-technological manifesto. This article focuses on Stemple Pass, Benning’s 2012 film that juxtaposes Kaczynski’s writings and the reconstruction of his cabin
GEOWALL® as a Quay wall
No full textBank protections are currently constructed with stone, wood, concrete and steel. NETICS has introduced a sustainable and commercially very attractive alternative called the GEOWALL. The goal of this study is to find a viable field of application within the quay structures by considering the arising challenges of a larger scale wall. Additionally several potential design improvements are described to cope with the challenges. The GEOWALL could fail due to sliding, overturning, exceeding internal stresses, large deformations, vertical instability, overall instability and piping. The safety of the structure will be assessed with predefined general factors of safety and permissible internal stresses, these are the test values. The safety for sliding, overturning, large deformations, vertical stability and piping is calculated with an analytical method. The safety for overall stability, internal strength and large deformations is calculated with a finite element method. There are two main variables in the analyses: the retaining height and the type of soil. The retaining height varies between one and five metres. The soils are simplified to sand, clay and peat. From the results of the analytical analysis and the finite element analysis it can be concluded that sand-GEOWALLs on sand between one and three metres and clay-GEOWALLs on clay between one and three metres are the most viable scenarios for a larger scale GEOWALL with current design. For GEOWALL quay walls larger than three metres and peat-GEOWALLs on peat suitable design improvements are required to meet the stringent safety requirements. The design improvements should be able to limit the possibility of failure due to sliding, overturning and failure trough large deformations. There are three categories of potential improvements: material improvements, geometrical design improvements and structural design improvements. The embedded wall is expected to be the most promising geometrical design improvement. Adding a drainage system is expected to be the most promising structural design improvement at this moment. It is recommended to study the effects and efficiency of the proposed design improvements in future research. It is also recommended for NETICS to continue their research on the strength and resistance of different GEOWALL types and on the influence of every possible load. In case of a GEOWALL design for a specific location it is recommended to determine the safety factors for that specific location and to check the analytical results with more advanced modelling programmes. Lastly it is recommended to consider not only the technical aspects, but also the practical and commercial aspects if one is investigating the design improvements.Hydraulic EngineeringCivil Engineering and Geoscience
Elucidating the role of N-acetylglucosamine in Group A Carbohydrate for the development of an effective glycoconjugate vaccine against Group A Streptococcus
No full textGroup A Carbohydrate (GAC), conjugated to an appropriate carrier protein, has been proposed as an attractive
vaccine candidate against Group A Streptococcus infections. Native GAC consists of a polyrhamnose (polyRha)
backbone with N-acetylglucosamine (GlcNAc) at every second rhamnose residue. Both native GAC and the
polyRha backbone have been proposed as vaccine components. Here, chemical synthesis and glycoengineering
were used to generate a panel of different length GAC and polyrhamnose fragments. Biochemical analyses were
performed confirming that the epitope motif of GAC is composed of GlcNAc in the context of the polyrhamnose
backbone. Conjugates from GAC isolated and purified from a bacterial strain and polyRha genetically expressed
in E. coli and with similar molecular size to GAC were compared in different animal models. The GAC conjugate
elicited higher anti-GAC IgG levels with stronger binding capacity to Group A Streptococcus strains than the
polyRha one, both in mice and in rabbits.
This work contributes to the development of a vaccine against Group A Streptococcus suggesting GAC as
preferable saccharide antigen to include in the vaccine
Towards real-time identification of brain tumors by integrating diffuse reflectance spectroscopy in a neurosurgical instrument
No full textBrain tumors account for approximately just 2% of all cancers worldwide, but have a noticeable impact on cancer morbidity and mortality. Removal of brain tumors poses a big challenge for neurosurgeons, pediatricians and neuro-oncologists. An important aspect of this challenge is to adequately differentiate between tumor tissue and healthy brain tissue. Tumors that are located within the eloquent cortex (functional brain cortex and major white matter fiber tracts) pose a particular surgical challenge due to the high risk of postoperative neurological deficits. Together with the In-Body Systems department of Philips Research and the Karolinska Institute in Sweden, the Delft University of Technology is participating in a new research focusing on adding diffuse reflectance spectroscopy in a neurosurgical instrument that can aid in better identifying the brain tumor margin. Previous research has used diffuse reflectance spectroscopy or a combination of diffuse reflectance and tissue fluorescence from endogenous (e.g., NADPH), exogenous (e.g., fluorescein), or exogenously induced fluorophores (e.g., PpIX) to identify spectral differences between healthy brain tissue and brain tumor tissue over a range of 400-900 nm. This master thesis presents the spectral differences between healthy and tumorous tissue over a range of 400-1600 nm, while using a spectroscopic tool, to better determine the demarcation of brain tumor margins with increased accuracy. The differences in optical characteristics in healthy brain tissue (i.e. white and gray matter) and human brain tumor tissue were identified. Furthermore, it was investigated whether the optical characteristics can provide a means to quantify the distinction between healthy and brain tumor tissue. Clear differences were found in the spectra between the different tissues. In the visible region higher values for the absorption coefficient were identified as indicators for tumor tissues. In the near infrared region clear distinctions in the diffuse reflectance spectra were observed between gray matter, tumor tissue and white matter, with gray matter presenting the highest value. The reduced scattering coefficient showed especially a clear distinction for white matter, presenting the highest values, compared to gray matter and tumor tissue. This was in line with the measurements of the scattering parameters and the fat fraction, with white matter presenting the highest value which can be explained due to its myelinated axons. For the other investigated parameters, an increased level of blood concentration and lower levels of StO2 were indicated as biomarkers for the tumor tissues. However, both physiological parameters are likely to change from in vivo to ex vivo settings which require that they should be investigated in in vivo experiments first before statements about their reliability can be made. The study was followed with a clinical workflow analysis, to identify the most promising neurosurgical instrument used during craniotomy in which diffuse reflectance spectroscopy can be integrated. Based on observations at brain tumor surgeries, open interviews with neurosurgeons and an investigation on several instruments, the suction cannula was found to be the most promising neurosurgical instrument to combine with diffuse reflectance spectroscopy. Finally, a prototype was designed and tested. In addition, it was investigated whether different amounts of suction power had an influence on the accuracy of the measured spectra while performing measurements with the prototype on healthy pig brain tissue. Overall, it can be concluded that spectral differences between healthy and tumorous tissue can be observed with the prototype and future research should increase the amount of data to verify these results. Furthermore, in vivo measurements should indicate whether these findings are consistent when the physiology of the tissues changes
Carbon Monoxide Dehydrogenase Reaction Mechanism: A Likely Case of Abnormal CO<sub>2</sub> Insertion to a Ni−H<sup>−</sup> Bond
No full textNi-containing carbon monoxide dehydrogenases (CODH), present in many anaerobic microorganisms, catalyze the reversible oxidation of CO to CO2 at the so-called C-cluster. This atypical active site is composed of a [NiFe3S4] cluster and a single unusual iron ion called ferrous component II or Feu that is bridged to the cluster via one sulfide ion. After additional refinement of recently published high-resolution structures of COOHx-, OHx-, and CN-bound CODH from Carboxydothermus hydrogenoformans (Jeoung and Dobbek Science 2007, 318, 1461−1464; J. Am. Chem. Soc. 2009, 131, 9922−9923), we have used computational methods on the predominant resulting structures to investigate the spectroscopically well-characterized catalytic intermediates, Cred1 and the two-electron more-reduced Cred2. Several models were geometry-optimized for both states using hybrid quantum mechanical/molecular mechanical potentials. The comparison of calculated Mössbauer parameters of these active site models with experimental data allows us to propose that the Cred1 state has a Feu−Ni2+ bridging hydroxide ligand and the Cred2 state has a hydride terminally bound to Ni2+. Using our combined structural and theoretical data, we put forward a revised version of an earlier proposal for the catalytic cycle of Ni-containing CODH (Volbeda and Fontecilla-Camps Dalton Trans. 2005, 21, 3443−3450) that agrees with available spectroscopic and structural data. This mechanism involves an abnormal CO2 insertion into the Ni2+−H− bond
- …
