Structure of the insect cytokine peptide plasmatocyte-spreading peptide 1 from Pseudoplusia includens

The structure of the recently identified plasmatocyte spreading peptide from the moth Pseudoplusia includens (PSP1) has been determined by NMR spectroscopy. This novel insect cytokine consists of 23 amino acid residues and a single disulfide bond. Torsion angle dynamics calculations utilizing a total of 337 distance constraints yielded an ensemble of 30 structures with an average backbone root mean square deviation for residues 7-22 of 0.18 A from the mean structure. The structure consists of a disordered N-terminal region and a well defined core that is stabilized by numerous hydrophobic interactions and a short beta-hairpin. Structural comparisons confirm that PSP1 adopts an epidermal growth factor (EGF)-like fold with close similarity to the C-terminal subdomain of EGF-like module 5 of human thrombomodulin. The combination of the three-dimensional structure of PSP1 and the extensive literature on EGF-receptor interactions should accelerate the process of identifying the specific residues responsible for receptor binding activity of this family of immunoregulatory peptides.     

Elevated expression of eIF4E in confined early breast cancer lesions: possible role of hypoxia

The translation-initiation factor eIF4E is rate-limiting for protein synthesis, and its over-expression results in oncogenic transformation of mammalian cells. eIF4E facilitates the synthesis of several powerful tumor angiogenic factors (FGF-2 and VEGF) by selectively enhancing their translation. In breast carcinomas, eIF4E is commonly over-expressed, but the pathology where this elevation is initially manifested is presently unknown. To probe whether the elevation of eIF4E marks an early stage of cancer development, we focused our research on early cancerous lesions. We have analyzed 70 invasive ductal carcinomas (IDCs), 78 ductal carcinomas in situ (DCIS), 51 benign lesions and 4 model cell lines for elevated expression of eIF4E by several different methods: Northern/Western blots, immuno-histochemistry and in situ RT-PCR. eIF4E expression was markedly increased in IDC and in islets of viable cells in the center of poorly vascularized DCIS, which are not easily identifiable by standard histological stains. We also show that expression of eIF4E is increased by hypoxia and, presumably, in hypoxic areas of these lesions. We propose that clonal expansion of cancer cells, permanently over-expressing eIF4E, gives them a critical advantage to survive hypoxia and marks the transition toward the vascular phase of cancer progression. Hence, eIF4E may be useful in stratifying DCIS lesions according to their malignant stage.     

Receiver array calibration using disparate sources

We present a new array calibration procedure for over-the-horizon (OTH) radar, using disparate sources. Unlike previous array calibration methods, which require a specific type or class of sources for calibrating the array, the method we propose can use combinations of single-mode, multimode, and near-field sources; each source with either known or unknown DOAs (directions-of-arrival). Multidimensional MUSIC is exploited for time-invariant DOA sources, while single-snapshot techniques are used for sources that have time-varying DOAs. A nonlinear separable least-squares solution to the array calibration problem is used to estimate the array coupling matrix and sensor positions. Simulation results indicate that good estimates are obtained for the unknown parameters and further the array sidelobe levels and bearing errors are significantly reduced when these estimated parameters are used in array processing. The algorithm performance was also compared with the Cramer-Rao lower bound and found to be statistically efficient     

Enhancing the multivariate signal of [15O] water PETstudies with a new nonlinear neuroanatomical registration algorithm [MRIapplication]

This paper addresses the problem of neuro-anatomical registration across individuals for functional [15O] water PET activation studies. A new algorithm for three-dimensional (3-D) nonlinear structural registration (warping) of MR scans is presented. The method performs a hierarchically scaled search for a displacement field, maximizing one of several voxel similarity measures derived from the two-dimensional (2-D) histogram of matched image intensities, subject to a regularizer that ensures smoothness of the displacement field. The effect of the nonlinear structural registration is studied when it is computed on anatomical MR scans and applied to coregistered [15O] water PET scans from the same subjects: in this experiment, a study of visually guided saccadic eye movements. The performance of the nonlinear warp is evaluated using multivariate functional signal and noise measures. These measures prove to be useful for comparing different intersubject registration approaches, e.g., affine versus nonlinear. A comparison of 12-parameter affine registration versus non-linear registration demonstrates that the proposed nonlinear method increases the number of voxels retained in the cross-subject mask. We demonstrate that improved structural registration may result in an improved multivariate functional signal-to-noise ratio (SNR). Furthermore, registration of PET scans using the 12-parameter affine transformations that align the coregistered MR images does not improve registration, compared to 12-parameter affine alignment of the PET images directly.     

Inversion of feedforward neural networks: algorithms andapplications

There are many methods for performing neural network inversion. Multi-element evolutionary inversion procedures are capable of finding numerous inversion points simultaneously. Constrained neural network inversion requires that the inversion solution belong to one or more specified constraint sets. In many cases, iterating between the neural network inversion solution and the constraint set can successfully solve constrained inversion problems. This paper surveys existing methodologies for neural network inversion, which is illustrated by its use as a tool in query-based learning, sonar performance analysis, power system security assessment, control, and generation of codebook vectors     

In vivo microdialysis of 2-deoxyglucose 6-phosphate into brain: a novel method for the measurement of interstitial pH using 31P-NMR

A unique method for simultaneously measuring interstitial (pHe) as well as intracellular (pHi) pH in the brains of lightly anesthetized rats is described. A 4-mm microdialysis probe was inserted acutely into the right frontal lobe in the center of the area sampled by a surface coil tuned for the collection of 31P-NMR spectra. 2-Deoxyglucose 6-phosphate (2-DG-6-P) was microdialyzed into the rat until a single NMR peak was detected in the phosphomonoester region of the 31P spectrum. pHe and pHi values were calculated from the chemical shift of 2-DG-6-P and inorganic phosphate, respectively, relative to the phosphocreatine peak. The average in vivo pHe was 7.24+/-0.01, whereas the average pHi was 7.05+/-0.01 (n = 7). The average pHe value and the average CSF bicarbonate value (23.5+/-0.1 mEq/L) were used to calculate an interstitial Pco2 of 55 mm Hg. Rats were then subjected to a 15-min period of either hypercapnia, by addition of CO2 (2.5, 5, or 10%) to the ventilator gases, or hypocapnia (PCO2 < 30 mm Hg), by increasing the ventilation rate and volume. pHe responded inversely to arterial Pco2 and was well described (r2 = 0.91) by the Henderson-Hasselbalch equation, assuming a pKa for the bicarbonate buffer system of 6.1 and a solubility coefficient for CO2 of 0.031. This confirms the view that the bicarbonate buffer system is dominant in the interstitial space. pHi responded inversely and linearly to arterial PCO2. The intracellular effect was muted as compared with pHe (slope = -0.0025, r2 = 0.60). pHe and pHi values were also monitored during the first 12 min of ischemia produced by cardiac arrest. pHe decreases more rapidly than pHi during the first 5 min of ischemia. After 12 min of ischemia, pHe and pHi values were not significantly different (6.44+/-0.02 and 6.44+/-0.03, respectively). The limitations, advantages, and future uses of the combined microdialysis/31P-NMR method for measurement of pHe and pHi are discussed.     

Lubrication in helical gears

In this paper, a method to determine elastohydrodynamic film thickness in helical gears is developed by combining the Dowson-Higginson elastohydrodynamic lubrication (EHL) formulation with helical gear geometry and kinematics. Comparisons are made with traditional gear film thickness models. This analysis is then used to characterise the film thickness and lambda ratio in an automotive planetary gearset. Methods to measure surface roughness in fine-pitch gears are described.     

Digestibility and Pasting Properties of Rice Starch Heat‐Moisture Treated at the Melting Temperature (Tm )

Non‐waxy and waxy rice starches adjusted to 20% moisture (wet based, w.b.) were heated in a differential scanning calorimeter to determine the optimum parameters for producing slowly digestible starch (SDS). Starches heated to the temperature of melting (T_m) and held for 60 min in the calorimeter showed a slow digestibility compared to unheated samples. Digestibility decreased by 25 and 10%, respectively, for non‐waxy and waxy rice starches relative to non‐treated starches. Heat‐moisture treatment of waxy corn, non‐waxy corn and wheat starches at the T_m determined for non‐waxy rice starch did not result in significant decreases in digestibility. For waxy rice starches heat‐treated in microwave or conventional ovens at the T_m , there were slight but significant increases in digestibility of the treated starches compared to non‐treated starches at all incubation times. Digestibility was higher for starches heated for 30 min than for 60 min. Non‐waxy rice starches did not show any significant changes in digestibility. Heat‐moisture treatment at the T_m and the holding time of sample at that temperature in a differential scanning calorimeter were found to be significant to the formation of slowly digestible heat‐moisture treated starch.     

Mouse Breast Carcinoma Monocytic/Macrophagic Myeloid-Derived Suppressor Cell Infiltration as a Consequence of Endothelial Dysfunction in Shb-Deficient Endothelial Cells Increases Tumor Lung Metastasis

Metastasis reflects both the inherent properties of tumor cells and the response of the stroma to the presence of the tumor. Vascular barrier properties, either due to endothelial cell (EC) or pericyte function, play an important role in metastasis in addition to the contribution of the immune system. The Shb gene encodes the Src homology-2 domain protein B that operates downstream of tyrosine kinases in both vascular and immune cells. We have investigated E0771.lmb breast carcinoma metastasis in mice with conditional deletion of the Shb gene using the Cdh5-Cre^ERt2 transgene, resulting in inactivation of the Shb-gene in EC and some hematopoietic cell populations. Lung metastasis from orthotopic tumors, tumor vascular and immune cell characteristics, and immune cell gene expression profiles were determined. We found no increase in vascular leakage that could explain the observed increase in metastasis upon the loss of Shb expression. Instead, Shb deficiency in EC promoted the recruitment of monocytic/macrophagic myeloid-derived suppressor cells (mMDSC), an immune cell type that confers a suppressive immune response, thus enhancing lung metastasis. An MDSC-promoting cytokine/chemokine profile was simultaneously observed in tumors grown in mice with EC-specific Shb deficiency, providing an explanation for the expanded mMDSC population. The results demonstrate an intricate interplay between tumor EC and immune cells that pivots between pro-tumoral and anti-tumoral properties, depending on relevant genetic and/or environmental factors operating in the microenvironment.