Selection of catalytically active biotin ligase and trypsin mutants by phage display

Phage display has been shown to facilitate greatly the selectionof polypeptides with desired properties by establishing a directlink between the polypeptide and the gene that encodes it. However,selection for catalytic activities displayed on phage remainsa challenge, since reaction products diffuse away from the enzymeand make it difficult to recover catalytically active phage–enzymes.We have recently described a selection methodology in whichthe reaction substrate (and eventually the reaction product)is anchored on calmodulin-tagged phage–enzymes by meansof a calmodulin binding peptide. Phage displaying a catalyticactivity are physically isolated by means of affinity reagentsspecific for the product of reaction. In this study, we investigatedthe efficiency of selection for catalysis by phage display,using a ligase (the Escherichia coli biotin ligase BirA) andan endopeptidase (the rat trypsin His57     

Molecular Biomarkers in Idiopathic Pulmonary Fibrosis: State of the Art and Future Directions

Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called “usual interstitial pneumonia” pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5–10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.     

Kinetic study of 1,5-cyclooctadiene hydro-isomerization on Pd/pumice catalysts

A new route for obtaining 1,4-cyclooctadiene by catalytic isomerization of 1,5-cyclooctadiene at low temperature in presence of H₂ in a three-phase reactor is presented. Wei, Prater and Silvestri methods are used for the kinetic studies. A comparison of the activity-selectivity patterns of the Pd/pumice catalysts with Pd on silica and Pt and Pd–Pt on pumice catalysts is performed. Although Pt catalysts are not active in the hydro-isomerization of 1,5-cyclooctadiene, the presence of small amount of Pt in Pd/pumice catalysts increases the yield to 1,4-cyclooctadiene. Besides the catalyst characteristics, temperature and H₂ pressure influence the production of 1,4-cyclooctadiene. A mechanism of the process is proposed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Opioids and attachment in rhesus macaque (Macaca mulatta) abusive mothers.

This study investigated the role of the endogenous opioid system in maternal and affiliative behavior of group-living rhesus macaque (Macaca mularta) mothers with a history of abusive parenting. 18 mothers received an injection of the opioid antagonist naltrexone or saline for 5 days per wk for the first 4 wks of the infant's life. After treatment, mother-infant pairs were focally observed. Naltrexone did not significantly affect infant abuse or other measures of maternal behavior. Naltrexone increased the amount of grooming received by mothers from other group members and reduced the mothers' rate of displacement activities such as scratching, yawning, and self-grooming. These results concur with previous primate studies in suggesting that opioids mediate the rewarding effects of receiving grooming and affect anxiety-related behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Compassion Practicum: A Capstone Design Experience at the United States Military Academy

A partnership has been developed linking the United States Military Academy and Special People in the Northeast, a non-profit agency for the mentally and physically handicapped children and adults based in Philadelphia. The present work documents a student design team's design and construction of a ticket-tearing device for a young man in the advanced stages of cerebral palsy and concludes with an evaluation of the entire process.     

Development and Experimental Analysis of a Soft Compliant Tactile Microsensor for Anthropomorphic Artificial Hand

This paper presents the development and preliminary experimental analysis of a soft compliant tactile microsensor (SCTM) with minimum thickness of 2 mm. A high shear sensitive triaxial force microsensor was embedded in a soft, compliant, flexible packaging. The performance of the whole system, including the SCTM, an electronic hardware and a processing algorithm, was evaluated by static calibration, maximum load tests, noise and dynamic tests, and by focusing on slippage experiments. A proper tradeoff between final robustness and sensitivity of the tactile device was identified. The experiments showed that the tactile sensor is sufficiently robust for application in artificial hands while sensitive enough for slip event detection. The sensor signals were elaborated with the cumulative summation algorithm and the results showed that the SCTM system could detect a slip event with a delay from a minimum of 24.5 ms to a maximum of 44 ms in the majority of experiments fulfilling the neurophysiological requirement.     

Probiotic-Induced Tolerogenic Dendritic Cells: A Novel Therapy for Inflammatory Bowel Disease?

Inflammatory bowel diseases (IBDs) are immune-mediated, chronic relapsing diseases with a rising prevalence worldwide in both adult and pediatric populations. Treatment options for immune-mediated diseases, including IBDs, are traditional steroids, immunomodulators, and biologics, none of which are capable of inducing long-lasting remission in all patients. Dendritic cells (DCs) play a fundamental role in inducing tolerance and regulating T cells and their tolerogenic functions. Hence, modulation of intestinal mucosal immunity by DCs could provide a novel, additional tool for the treatment of IBD. Recent evidence indicates that probiotic bacteria might impact immunomodulation both in vitro and in vivo by regulating DCs’ maturation and producing tolerogenic DCs (tolDCs) which, in turn, might dampen inflammation. In this review, we will discuss this evidence and the mechanisms of action of probiotics and their metabolites in inducing tolDCs in IBDs and some conditions associated with them.     

Laser Melting of Spark Plasma-Sintered Zirconium Carbide: Thermophysical Properties of a Generation IV Very High-Temperature Reactor Material

Melting temperatures of zirconium carbide were investigated in validating a novel thermal analysis technique for refractory materials. Commercial ZrC_0.96 powder was densified by spark plasma sintering to >96% relative density after 6–30 min at 2173–2453 K under 40–100 MPa. Sintered ceramics were heated to >4000 K via pulsed laser heating. Mean values for solidus and liquidus transitions were 3451 and 3608 K, respectively, in fair agreement with the present phase diagram. Postmelting analysis revealed dendritic microstructure and composition consistent with single-phase ZrC. Subsurface gas porosity and ZrC–C eutectic indicate complex processes occurring during melting and freezing.     

Mixed bi-material electrodes based on LiMn2O4 and activated carbon for hybrid electrochemical energy storage devices

The performance of mixed bi-material electrodes composed of the battery material, LiMn₂O₄, and the electrochemical capacitor material, activated carbon, for hybrid electrochemical energy storage devices is investigated by galvanostatic charge/discharge and pulsed discharge experiments. Both, a high and a low conductivity lithium-containing electrolyte are used. The specific charge of the bi-material electrode is the linear combination of the specific charges of LiMn₂O₄ and activated carbon according to the electrode composition at low discharge rates. Thus, the specific charge of the bi-material electrode falls between the specific charge of the activated carbon electrode and the LiMn₂O₄ battery electrode. The bi-material electrodes have better rate capability than the LiMn₂O₄ battery electrode. For high current pulsed applications the bi-material electrodes typically outperform both the battery and the capacitor electrode.