Structural Insights into the Design of Synthetic Nanobody Libraries

Single domain antibodies from camelids, or nanobodies, are a unique class of antibody fragments with several advantageous characteristics: small monomeric size, high stability and solubility and easy tailoring for multiple applications. Nanobodies are gaining increasing acceptance as diagnostic tools and promising therapeutic agents in cancer and other diseases. While most nanobodies are obtained from immunized animals of the camelid family, a few synthetic nanobody libraries constructed in recent years have shown the capability of generating high quality nanobodies in terms of affinity and stability. Since this synthetic approach has important advantages over the use of animals, the recent advances are indeed encouraging. Here we review over a dozen synthetic nanobody libraries reported so far and discuss the different approaches followed in their construction and validation, with an emphasis on framework and hypervariable loop design as critical issues defining their potential as high-class nanobody sources.     

Production and Digestibility Studies of β-Galactosyl Xylitol Derivatives Using Heterogeneous Catalysts of LacA β-Galactosidase from Lactobacillus Plantarum WCFS1

The synthesis of β-galactosyl xylitol derivatives using immobilized LacA β-galactosidase from Lactobacillus plantarum WCFS1 is presented. These compounds have the potential to replace traditional sugars by their properties as sweetener and taking the advantages of a low digestibility. The enzyme was immobilized on different supports, obtaining immobilized preparations with different activity and stability. The immobilization on agarose-IDA-Zn-CHO in the presence of galactose allowed for the conserving of 78% of the offered activity. This preparation was 3.8 times more stable than soluble. Since the enzyme has polyhistidine tags, this support allowed the immobilization, purification and stabilization in one step. The immobilized preparation was used in synthesis obtaining two main products and a total of around 68 g/L of β-galactosyl xylitol derivatives and improving the synthesis/hydrolysis ratio by around 30% compared to that of the soluble enzyme. The catalyst was recycled 10 times, preserving an activity higher than 50%. The in vitro intestinal digestibility of the main β-galactosyl xylitol derivatives was lower than that of lactose, being around 6 and 15% for the galacto-xylitol derivatives compared to 55% of lactose after 120 min of digestion. The optimal amount immobilized constitutes a very useful tool to synthetize β-galactosyl xylitol derivatives since it can be used as a catalyst with high yield and being recycled for at least 10 more cycles.     

Stereoisomeric Tris-BINOL-Menthol Bulky Monophosphites: Synthesis,Characterisation and Application in Rhodium-Catalysed Hydroformylation

Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (−)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)₂(acac), was attested by ³¹P NMR, which presented a doublet in the range of δ = 120 ppm, with a ¹J(¹⁰³Rh-³¹P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm⁻¹ and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene.     

Excited-state absorption and 1064-nm end-pumped laser emission of Nd:YVO4 single-crystal fiber grown by laser-heated pedestal growth

We present an investigation of the excited-state absorption and laser emission of a 1.0-at. %-Nd3+-doped YVO4 single-crystal fiber grown by the low-cost and versatile laser-heated pedestal growth technique. Efficient laser emission at 1064 nm was achieved when the fiber was pumped, in an end-pump cavity, by a Ti:sapphire laser at 808 nm. A continuous-wave threshold of 10 mW was observed with an efficiency of 42% with respect to the absorbed pump power and the maximum output power of 200 mW. These results are excellent when compared with those of a commercial bulk crystal adapted to the same cavity (48% efficiency, 250-mW maximum output power). Thus the fibers are characterized as strong candidates for the construction of compact lasers that can also be pumped by low-cost diode lasers.     

New class of level statistics in correlated disordered chains

We study the properties of the level statistics of 1D disordered systems with long-range spatial correlations. We find a threshold value in the degree of correlations below which in the limit of large system size the level statistics follows a Poisson distribution (as expected for 1D uncorrelated-disordered systems), and above which the level statistics is described by a new class of distribution functions. At the threshold, we find that with increasing system size, the standard deviation of the function describing the level statistics converges to the standard deviation of the Poissonian distribution as a power law. Above the threshold we find that the level statistics is characterized by different functional forms for different degrees of correlations.     

Using an ANP performance management framework to manage the development of transversal competences in University degrees

Organisations are concerned about measuring the performance of the product/service they deliver to their customers. In all types of organisations, if a proper performance assessment is to be developed, it should be measured in different dimensions. At University, the new study programs include the development and assessment of transversal competences due to their importance in enhancing the abilities and improving the employability of students. The achievement of transversal competences can be assessed in different levels/stages; for example, the 1st and 2nd years of a Bachelor’s degree; the 3rd and 4th years of a Bachelor’s degree and at Master’s level. The purpose of this paper is to integrate the research into performance management in organisations to develop an approach consisting of four components (a methodology, a solid and integrated performance management framework, graphical diagrams and quantitative techniques) to assess and manage the achievement of transversal competences through the different levels of study using a consolidated approach. The proposal uses the Analytic Network Process (ANP) to model dependences and feedback among the elements of the competences.

     

Robustness to measurement noise of a globally convergent attitude observer with topological relaxations

Nonlinear Dynamics - In the past decade, substantial effort has been put in the design of attitude observers with bias estimation that present both stability and convergence guarantees. However,...     

Determination of cocaine adulterants in human urine by dispersive liquid-liquid microextraction and high-performance liquid chromatography

Analytical and Bioanalytical Chemistry - This study aimed to determine simultaneously five major street cocaine adulterants (caffeine, lidocaine, phenacetin, diltiazem, and hydroxyzine) in human...