Brain Modules and Their Multiple Ways of Knowing: Implications for the Unity of the Person

This paper was prepared for the Ways of Knowing in Concert conference held at Dordt College, August 12-15, 1998

Our Fragile Brains (Book Review)

Reviewed Title: Our Fragile Brains, by D. Gareth Jones. Downers Grove, IL: InterVarsity Press, 1981, 278 pp

Mind Fields: Reflections on the Science of Mind and Brain (Book Review)

Reviewed Title: Mind Fields: Reflections on the Science of Mind and Brain, by Malcolm Jeeves (Baker Books: Grand Rapids, 1994). 135 pages

Wind-tunnel investigation of a flush airdata system at Mach numbers from 0.7 to 1.4

Flush pressure orifices installed on the nose section of a 1/7-scale model of the F-14 airplane were evaluated for use as a flush airdata system (FADS). Wing-tunnel tests were conducted in the 11- by 11-ft Unitary Wind Tunnel at NASA Ames Research Center. A full-scale FADS of the same configuration was previously tested using an F-14 aircraft at the Dryden Flight Research Facility of NASA Ames Research Center (Ames-Dryden). These tests, which were published, are part of a NASA program to assess accuracies of FADS for use on aircraft. The test program also provides data to validate algorithms for the shuttle entry airdata system developed at the NASA Langley Research Center. The wind-tunnel test Mach numbers were 0.73, 0.90, 1.05, 1.20, and 1.39. Angles of attack were varied in 2 deg increments from -4 deg to 20 deg. Sideslip angles were varied in 4 deg increments from -8 deg to 8 deg. Airdata parameters were evaluated for determination of free-stream values of stagnation pressure, static pressure, angle of attack, angle of sideslip, and Mach number. These parameters are, in most cases, the same as the parameters investigated in the flight test program. The basic FADS wind-tunnel data are presented in tabular form. A discussion of the more accurate parameters is included

Quantitative Proteomic (iTRAQ) Analysis of 1st Trimester Maternal Plasma Samples in Pregnancies at Risk for Preeclampsia

A current major obstacle is that no reliable screening markers exist to detect pregnancies at risk for preeclampsia. Quantitative proteomic analysis employing isobaric labelling (iTRAQ) has been suggested to be suitable for the detection of potential plasma biomarkers, a feature we recently verified in analysis of pregnancies with Down syndrome foetuses. We have now examined whether this approach could yield biomarkers to screen pregnancies at risk for preeclampsia. In our study, we used maternal plasma samples obtained at 12 weeks of gestation, six from women who subsequently developed preeclampsia and six with uncomplicated deliveries. In our analysis, we observed elevations in 10 proteins out of 64 proteins in the preeclampsia study group when compared to the healthy control group. These proteins included clusterin, fibrinogen, fibronectin, and angiotensinogen, increased levels of which are known to be associated with preeclampsia. An elevation in the immune-modulatory molecule, galectin 3 binding protein, was also noted. Our pilot study, therefore, indicates that quantitative proteomic iTRAQ analysis could be a useful tool for the detection of new preeclampsia screening markers

The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates

In yeast TOR and PKA pathways both control cell growth but how TORC1 and PKA signaling are linked is unknown. Here we show that TORC1 inhibition prevents the phosphorylation of some but not all PKA targets. We further demonstrate that TORC1 controls PKA by inhibiting the phosphorylation of the PKA regulatory subunit BCY1 by the MAP kinase MPK1

Quantitative Proteomics Analysis of Maternal Plasma in Down Syndrome Pregnancies Using Isobaric Tagging Reagent (iTRAQ)

Currently no specific biomarkers exist for the screening of pregnancies at risk for down syndrome (DS). Since a quantitative proteomic approach with isobaric labelling (iTRAQ) has recently been suggested to be highly suitable for the discovery of novel plasma biomarkers, we have now used this method to examine for potential quantitative changes in the plasma proteome of the pregnancies bearing DS fetuses in comparison to normal healthy babies. In our study, we used plasma from six women with DS pregnancies and six with uncomplicated pregnancies care were taken to match cases and controls for gestational and maternal age, as these could be a confounder. In our quantitative proteomics analysis we were able to detect 178 proteins using iTRAQ labelling in conjunction with 4800 MALDI TOF/TOF. Amongst these we observed changes in βHCG, a known screening marker for DS, indicating that our assay was functional. We found a number of elevated proteins Ig lambda chain C region, serum amyloid P-component, amyloid beta A4, and under expressed proteins like gamma-actin and titin in DS pregnancies. These proteins are also found in the sera of patients with Alzheimer disease, which share similar pathologies of DS. Our study therefore indicates that the iTRAQ labelling approach may be indeed useful for the detection of novel biomarkers

Quantitative Proteomics of Spodoptera frugiperda Cells during Growth and Baculovirus Infection

Baculovirus infection of Spodoptera frugiperda cells is a system of choice to produce a range of recombinant proteins, vaccines and, potentially, gene therapy vectors. While baculovirus genomes are well characterized, the genome of S. frugiperda is not sequenced and the virus-host molecular interplay is sparsely known. Herein, we describe the application of stable isotope labeling by amino acids in cell culture (SILAC) to obtain the first comparative proteome quantitation of S. frugiperda cells during growth and early baculovirus infection. The proteome coverage was maximized by compiling a search database with protein annotations from insect species. Of interest were differentially proteins related to energy metabolism, endoplasmic reticulum and oxidative stress, yet not investigated in the scope of baculovirus infection. Further, the reduced expression of key viral-encoded proteins early in the infection cycle is suggested to be related with decreased viral replication at high cell density culture. These findings have implications for virological research and improvement of baculovirus-based bioprocesses

A levodopa dry powder inhaler for the treatment of Parkinson's disease patients in off periods

Adequate treatment of Parkinson's patients in off periods with orally administered levodopa is hindered by a poor bioavailability and a slow onset of action. Hence, there is a need for a fast and reliable alternative as for instance via pulmonary administration of the drug. We developed a levodopa containing powder formulation for pulmonary delivery by a recently presented high dose dry powder inhaler (Cyclops). The objective was to produce the drug formulation by means of simple techniques such as micronization, either as pure active substance or with a minimum amount of excipients. After an initial screening on dispersion behaviour, the most promising formulation in the Cyclops was characterized in vitro over a range of pressure drops (2-6 kPa) and doses (20, 30 and 40 mg), representative of those to be expected in practice. A co-micronized levodopa formulation with 2% l-leucine appeared to yield the best aerosol properties for inhalation and highest delivered dose reproducibility. The combination of this particular formulation and the Cyclops inhaler seems to meet the basic requirements for satisfactory deposition in the airways. This formulation is therefore expected to be a promising candidate for the treatment of Parkinson's patients in an off period