Crossing the Border: From Keto- to Imine Reduction in Short-Chain Dehydrogenases/Reductases

The family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDRs) comprises numerous biocatalysts capable of C=O or C=C reduction. The highly homologous noroxomaritidine reductase (NR) from Narcissus sp. aff. pseudonarcissus and Zt_SDR from Zephyranthes treatiae, however, are SDRs with an extended imine substrate scope. Comparison with a similar SDR from Asparagus officinalis (Ao_SDR) exhibiting keto-reducing activity, yet negligible imine-reducing capability, and mining the Short-Chain Dehydrogenase/Reductase Engineering Database indicated that NR and Zt_SDR possess a unique active-site composition among SDRs. Adapting the active site of Ao_SDR accordingly improved its imine-reducing capability. By applying the same strategy, an unrelated SDR from Methylobacterium sp. 77 (M77_SDR) with distinct keto-reducing activity was engineered into a promiscuous enzyme with imine-reducing activity, thereby confirming that the ability to reduce imines can be rationally introduced into members of the “classical” SDR enzyme family. Thus, members of the SDR family could be a promising starting point for protein approaches to generate new imine-reducing enzymes.     

Using an integrated process of data and modeling in HRA

The paper describes an approach taken to estimate the probabilities of failure associated with various railroad tasks to prevent accidents (principally collisions and derailments). These probabilities were estimated using an expert elicitation process that used partially relevant data available from a variety of databases and that were filtered and scaled to make them more directly relevant to the analyses being performed. Extensive qualitative studies were performed prior to the elicitation process to identify relevant contexts under which the tasks can be performed.     

Wavelength-tunable 40-GHz picosecond harmonically mode-locked fiber laser source

We demonstrate a novel 40-GHz mode-locked fiber laser that utilizes a single active device to provide both gain and mode-locking. The laser produces pulses as short as 2.2 ps, is tunable over a 27-nm band centered at 1553 nm, and exhibits long-term stability without cavity-length feedback control. The pulse train at 1556 nm was used in a 40-Gb/s transmission experiment over 45 km with a low 0.4-dB power penalty.     

Respiratory mechanics during mechanical ventilation: a model study on the effects of leak around a tracheal tube

Recently published studies indicate a potential clinical application of PET in head and neck tumors. In the preoperative staging phase, PET enables confirmation of regional lymph node extension and guides nodal neck dissection or systemic treatment. In this phase, a high negative predictive value, near 100%, could make it possible to avoid many negative neck dissections. This is a reliable technique for confirming or excluding the presence of recurrent/residual tumor and for obtaining an early evaluation of chemotherapeutic and radiotherapeutic response. PET imaging in many cases makes it possible to locate and guide histological study of tumors with an unknown primary. PET imaging for these indications is a perfect complementary method for clinical exploration and better than other imaging techniques.     

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB), a neural member of the EGF family of differentiation factors, is implicated in neurite formation

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB) was identified by combining binding assays with immunological screens in the chicken nervous system as a novel member of the EGF family of differentiation factors. cDNA cloning indicates that CALEB is a multidomain protein that consists of an NH2-terminal glycosylation region, a leucine-proline-rich segment, an acidic box, a single EGF-like domain, a transmembrane, and a short cytoplasmic stretch. In the developing nervous system, CALEB is associated with glial and neuronal surfaces. CALEB is composed of a 140/130-kD doublet, an 80-kD band, and a chondroitinsulfate-containing 200-kD component. The latter two components are expressed in the embryonic nervous system and are downregulated in the adult nervous system. CALEB binds to the extracellular matrix glycoproteins tenascin-C and -R. In vitro antibody perturbation experiments reveal a participation of CALEB in neurite formation in a permissive environment.