Customizing MRI-Compatible Multifunctional Neural Interfaces through Fiber Drawing

Fiber drawing enables scalable fabrication of multifunctional flexible fibers that integrate electrical, optical, and microfluidic modalities to record and modulate neural activity. Constraints on thermomechanical properties of materials, however, have prevented integrated drawing of metal electrodes with low-loss polymer waveguides for concurrent electrical recording and optical neuromodulation. Here, two fabrication approaches are introduced: 1) an iterative thermal drawing with a soft, low melting temperature (T_m) metal indium, and 2) a metal convergence drawing with traditionally non-drawable high T_m metal tungsten. Both approaches deliver multifunctional flexible neural interfaces with low-impedance metallic electrodes and low-loss waveguides, capable of recording optically-evoked and spontaneous neural activity in mice over several weeks. These fibers are coupled with a light-weight mechanical microdrive (1 g) that enables depth-specific interrogation of neural circuits in mice following chronic implantation. Finally, the compatibility of these fibers with magnetic resonance imaging is demonstrated and they are applied to visualize the delivery of chemical payloads through the integrated channels in real time. Together, these advances expand the domains of application of the fiber-based neural probes in neuroscience and neuroengineering.     

Derivatization of Antibody Fab Fragments: A Designer Enzyme for Native Protein Modification

Bioconjugates, such as antibody–drug conjugates, have gained recent attention because of their increasing use in therapeutic and diagnostic applications. Commonly used conjugation reactions based upon chemoselective reagents exhibit a number of drawbacks: most of these reactions lack regio‐ and stereospecificity, thus resulting in loss of protein functionality due to random modifications. Enzymes provide an obvious solution to this problem, but the intrinsic (natural) substrate specificities of existing enzymes pose severe limitations to the kind of modifications that can be introduced. Here we describe the application of the novel trypsin variant trypsiligase for site‐specific modification of the C terminus of a Fab antibody fragment via a stable peptide bond. The suitability of this designed biocatalyst was demonstrated by coupling the Her2‐specific Fab to artificial functionalities of either therapeutic (PEG) or diagnostic (fluorescein) relevance. In both cases we obtained homogeneously modified Fab products bearing the artificial functionality exclusively at the desired position.     

Structural and Biochemical Studies of Actin in Complex with Synthetic Macrolide Tail Analogues

The actin filament‐binding and filament‐severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine C (SF‐01 and GC‐04) are shown to bind to G‐actin with dissociation constants of (285±33) and (132±13) nM , respectively. The crystal structures of actin complexes with GC‐04, SF‐01, and kabiramide C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region to the SD1/SD3 cleft on the upper protomer, which displaces loop‐D from the lower protomer on the same half‐filament. With previous studies showing that the GC‐04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F‐actin would make them more effective at severing filaments compared with plasma gelsolin. Structure‐based analyses are used to suggest more reactive or targetable forms of GC‐04 and SF‐01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis.     

Anytime approximation in probabilistic databases

This article describes an approximation algorithm for computing the probability of propositional formulas over discrete random variables. It incrementally refines lower and upper bounds on the probability of the formulas until the desired absolute or relative error guarantee is reached. This algorithm is used by the SPROUT query engine to approximate the probabilities of results to relational algebra queries on expressive probabilistic databases.     

Modellbasierte Entscheidungsunterstützung in Produktions- und Dienstleistungsnetzwerken

In this paper, we sketch some of the challenges that should be addressed in future research efforts for model-based decision support in manufacturing and service networks. This includes integration issues, taking into account the autonomy of the decision-making entities in face of information asymmetry, the modeling of preferences of the decision-makers, efficiently determining robust solutions, i.e. solutions that are insensitive with respect to changes in the problem data, and a reduction of the time needed for model building and usage. The problem solution cycle includes problem analysis, the design of appropriate algorithms and their performance assessment. We are interested in a prototypical integration of the proposed methods within application systems, which can be followed up with field tests of the extended application systems. We argue that the described research agenda requires the interdisciplinary collaboration of business and information systems engineering researchers with colleagues from management science, computer science, and operations research. In addition, we present some exemplifying, illustrative examples of relevant research results.     

Corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: baseline prevalence and repeatability of detection

Fibroblast growth factor-16 (FGF-16) is the most recent member of the FGF family to be cloned. Since the biologic activity of rat FGF-16 (rFGF-16) was unknown, and this protein has no apparent signal sequence, we transformed its entire cDNA into Escherichia coli for high-level expression and further characterization of this novel protein. An attempt was made to purify the expressed protein from the supernatant of mechanically lysed cells using sequential cation-exchange chromatography. This resulted in a gradual loss of the protein as precipitate throughout the purification process. In addition to precipitation during purification, sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the partially purified materials showed a cluster of protein bands around 20k to 29k. Sequence analysis of the major bands indicated that two N-terminal truncations had occurred, during E. coli fermentation, purification, or both. The largest truncation resulted in the removal of the 34 N-terminal amino acids, including the initiation codon methionine. We cloned d34 rFGF-16, expressed the gene in E. coli, and developed a purification process for this form. Even with this truncated form, precipitation was a problem. We were largely able to overcome this problem, however, by including EDTA throughout the purification process. We have characterized the structure of purified d34 rFGF-16 extensively using circular dichroism, Fourier transform infrared spectroscopy, and sedimentation velocity analysis. These studies revealed that the protein has a distinct tertiary structure, consists primarily of beta-strands, has a weak tendency to self-associate, and is fairly extended. We then performed biologic assays which showed that d34 rFGF-16 induces oligodendrocyte proliferation in vitro, and induces hepatocellular proliferation and increased liver weight in vivo. In summary, FGF-16, a novel FGF family member, has both unique structural and biological properties.     

Visible skin condition and perception of human facial appearance

Evolutionary psychology suggests that certain human beauty standards have evolved to provide reliable cues of fertility and health. Hence, preferences for some physical characteristics of the face and body are thought to reflect adaptations for the promotion of mate choice. Studies that have investigated facial attractiveness have concentrated mainly on features such as symmetry, averageness and sex‐typical traits, which are developed under the influence of sex steroids. Few studies, however, have addressed the effect of human skin condition on perception of facial appearance in this context, and possible implications for sexual selection. There is now accumulating evidence that skin pigmentation and skin surface topography cues, particularly in women, have a significant influence on attractiveness judgements, as they seem primarily to signal aspects of age and health. This article (i) reviews briefly some of the main determinants of visible skin condition, (ii) presents recent evidence on its signalling value in face perception and (iii) suggests areas for future research with reference to an evolutionary psychology framework.     

CO2 LASER PHOTOACOUSTIC SPECTROSCOPY AND ABSOLUTE ABSORPTION COEFFICIENTS OF SHORT CHAIN SATURATED FATTY ACID VAPOURS

Abstract

A resonant photoacoustic cell, capable of contamination free operation at temperatures above that of the ambient, was constructed and used to determine absolute absorption coefficients of C6:0 (hexanoic) and C8:0 (octanoic) fatty acid vapours at CO₂ laser wavelengths. At atmospheric pressure, the maximum absorption coefficients at the 9R(32) line of the CO₂ laser (1085.77cm^?1) are 8.0 atm^?1 cm^?1 (C6:0 at 332K) and 8.9 atm^?1 cm^?1 (C8:0 at 342 K).